Phapanin Charoenphol
- Courses2
- Reviews15
- School: Texas A&M University
- Campus: College Station
- Department: Mechanical Engineering
- Email address: Join to see
- Phone: Join to see
-
Location:
College Station, TX - Dates at Texas A&M University: April 2017 - July 2020
- Office Hours: Join to see
N/A
Would take again: Yes
For Credit: Yes
0
0
Not Mandatory
Awesome
Prof. Phapanin is very responsive and caring. She helped me make up for the homework I missed even if it was already 2+ weeks late. Grading structure is straightforward and her lectures are clear. Exams are tough but she's still the best thermo prof!
N/A
Would take again: Yes
For Credit: Yes
0
0
Mandatory
Good
Prof. Phapanin is an amazing thermo prof! Her exams tend to be harder than other profs, but it's okay because she teaches really clearly! At the end of the class, she even gave a slight curve. You'll do fine as long as you practice the homework and pay attention in class.
N/A
Would take again: No
For Credit: Yes
1
0
Mandatory
Poor
Professor Charoenphol is not great. She made thermodynamics more difficult than electricity and magnetism. The tests were nothing like homework. She always pulled something out of nowhere to confuse us. She's a harsh grader and will not help you, even to slightly bump your grade out of the 60's. Also, she doesn't post her notes online and has no example problems.
Biography
Texas A&M University College Station - Mechanical Engineering
Experience
Thai Caprolactam Public Company Limited
Undergraduate Intern
• Utilized HYSYS simulation software to model cyclohexanone distillation section and examined the optimal operating conditions which enhanced the process efficiency.
• Designed a new piping system of deionized water returning lines to optimize their usage in a storage plant.Texas A&M University
Research Assistant Professor
Phapanin worked at Texas A&M University as a Research Assistant Professor
University of Michigan
Research Assistant
• Developed white blood cell-mimicked particulate carriers for selectively delivering therapeutics to inflamed tissues.
• Elucidated the impact of human blood cells and the influence of carrier materials on the circulation and distribution of the particulate carriers in human vasculature models.
• Determined an optimal spherical carrier’s size (~2 μm) for intravenous drug delivery in atherosclerosis via developed in vitro assays and apolipoprotein E knockout mice models.
• Demonstrated the effect of blood rheology of several animal models, including mouse, pig, goat and cow, on dictating the localization of drug carriers to the target tissues.University of Michigan
Graduate Student Instructor
• Lectured and supervised undergraduate students in Heat and Mass Transfer class.
University of Melbourne
Undergraduate Research Assistant
• Optimized surface treatments to create superhydrophobic porous polypropylene membranes – used in membrane contacting processes for capturing and separating carbon dioxide from flue gases.
University of Massachusetts Amherst
Post Doctoral Associate, Polymer Science and Engineering
• Designed novel DNA-based nanostructures as a non-viral vector for targeted treatment in cancer.
This delivery system demonstrated minimal cytotoxicity and enhanced transfection efficiency of nucleic acids.
• Developed a multifunctional DNA nanostructure platform for co-delivering multiple therapeutics (e.g., AS1411 aptamer and BCL-2 antisense), and investigating their therapeutic synergy on antitumor efficacy.
• Conducted pre-clinical pharmacokinetic studies of DNA-based vehicles in CD-1 mice
Education
University of Michigan
Doctor of Philosophy (Ph.D.)
Chemical Engineering
University of Michigan
Master of Science (M.S.)
Chemical Engineering
University of Michigan
Research Assistant
• Developed white blood cell-mimicked particulate carriers for selectively delivering therapeutics to inflamed tissues. • Elucidated the impact of human blood cells and the influence of carrier materials on the circulation and distribution of the particulate carriers in human vasculature models. • Determined an optimal spherical carrier’s size (~2 μm) for intravenous drug delivery in atherosclerosis via developed in vitro assays and apolipoprotein E knockout mice models. • Demonstrated the effect of blood rheology of several animal models, including mouse, pig, goat and cow, on dictating the localization of drug carriers to the target tissues.University of Michigan
Graduate Student Instructor
• Lectured and supervised undergraduate students in Heat and Mass Transfer class.Chulalongkorn University, Thailand
Bachelor's degree
Chemical Engineering
Publications
Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery
Journal of Biomechanics
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres – but not nanospheres – from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery
Journal of Biomechanics
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres – but not nanospheres – from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review)
Molecular Membrane Biology
Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse blood hemodynamics and rheology, and the natural clearance process that tend to decrease the circulation time of foreign particles all lessen the probability of successful carrier interaction with the vascular wall. An effective vascular-targeted drug delivery system must be able to navigate through the bloodstream while avoiding immune clearance, attach to the vascular wall, and release its therapeutic cargo at the intended location. This review will summarize and analyze current literature reporting on (1) nanocarrier fabrication methods and materials that allow for optimum therapeutic encapsulation, protection, and release; (2) localization and binding dynamics of nanocarriers as influenced by hemodynamics and blood rheology in medium-to-large vessels; (3) blood cells' responses to various types of nanocarrier compositions and its effects on particle circulation time; and (4) properties that affect nanocarrier internalization at the target site.
Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery
Journal of Biomechanics
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres – but not nanospheres – from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review)
Molecular Membrane Biology
Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse blood hemodynamics and rheology, and the natural clearance process that tend to decrease the circulation time of foreign particles all lessen the probability of successful carrier interaction with the vascular wall. An effective vascular-targeted drug delivery system must be able to navigate through the bloodstream while avoiding immune clearance, attach to the vascular wall, and release its therapeutic cargo at the intended location. This review will summarize and analyze current literature reporting on (1) nanocarrier fabrication methods and materials that allow for optimum therapeutic encapsulation, protection, and release; (2) localization and binding dynamics of nanocarriers as influenced by hemodynamics and blood rheology in medium-to-large vessels; (3) blood cells' responses to various types of nanocarrier compositions and its effects on particle circulation time; and (4) properties that affect nanocarrier internalization at the target site.
Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels
Langmuir
Many variants of vascular-targeted carriers (VTCs) have been investigated for therapeutic intervention in several human diseases. However, in order to optimize the functionality of VTC in vivo, carriers’ physical properties, such as size and shape, are important considerations for a VTC design that evades the reticuloendothelial system (RES) and successfully interacts with the targeted vessel wall. Nonetheless, little evidence has been presented on the role of size in VTC’s interactions with the vascular wall, particularly in the microcirculation. Thus, in this work, we explore how particle size, along with hemodynamics (blood shear rate and vessel size) and hemorheology (blood hematocrit) affect the capacity for spheres to marginate (localize and adhere) to inflamed endothelium in a microfluidic model of human microvessels. Microspheres, particularly the 2 μm spheres, were found to show disproportionately higher margination than nanospheres in all hemodynamic conditions evaluated due to the poor ability of the latter to localize to the wall region from midstream. This work represents the first evidence that nanospheres may not exhibit “near wall excess” in microvessels, e.g., arterioles and venules, and therefore may not be suitable for imaging and drug delivery applications in cancer and other diseases affecting microvessels.
Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery
Journal of Biomechanics
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres – but not nanospheres – from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review)
Molecular Membrane Biology
Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse blood hemodynamics and rheology, and the natural clearance process that tend to decrease the circulation time of foreign particles all lessen the probability of successful carrier interaction with the vascular wall. An effective vascular-targeted drug delivery system must be able to navigate through the bloodstream while avoiding immune clearance, attach to the vascular wall, and release its therapeutic cargo at the intended location. This review will summarize and analyze current literature reporting on (1) nanocarrier fabrication methods and materials that allow for optimum therapeutic encapsulation, protection, and release; (2) localization and binding dynamics of nanocarriers as influenced by hemodynamics and blood rheology in medium-to-large vessels; (3) blood cells' responses to various types of nanocarrier compositions and its effects on particle circulation time; and (4) properties that affect nanocarrier internalization at the target site.
Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels
Langmuir
Many variants of vascular-targeted carriers (VTCs) have been investigated for therapeutic intervention in several human diseases. However, in order to optimize the functionality of VTC in vivo, carriers’ physical properties, such as size and shape, are important considerations for a VTC design that evades the reticuloendothelial system (RES) and successfully interacts with the targeted vessel wall. Nonetheless, little evidence has been presented on the role of size in VTC’s interactions with the vascular wall, particularly in the microcirculation. Thus, in this work, we explore how particle size, along with hemodynamics (blood shear rate and vessel size) and hemorheology (blood hematocrit) affect the capacity for spheres to marginate (localize and adhere) to inflamed endothelium in a microfluidic model of human microvessels. Microspheres, particularly the 2 μm spheres, were found to show disproportionately higher margination than nanospheres in all hemodynamic conditions evaluated due to the poor ability of the latter to localize to the wall region from midstream. This work represents the first evidence that nanospheres may not exhibit “near wall excess” in microvessels, e.g., arterioles and venules, and therefore may not be suitable for imaging and drug delivery applications in cancer and other diseases affecting microvessels.
Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers
Biomaterials
Targeting of drug carriers to the vascular wall is of interest for localized delivery of therapeutics in many human diseases. Nanometer-sized spherical particles are widely proposed for use as carriers for vascular targeting, yet very little evidence has been presented as to their ability to interact with the vascular wall. Thus, this work focuses on elucidating the effect of particle size along with hemodynamics, blood rheology, and vessel size on the adhesion efficiency of targeted polymeric spheres to inflamed endothelium in vitro via parallel plate flow chamber assays. We find that the binding efficiency of spheres to the endothelium from blood flow generally increased with increasing particle size, wall shear rate and channel height for particle sizes from 100 nm up to 10 μm. However, nano-sized particles showed minimal adhesion to the endothelium from blood flow in horizontal (gravity or anti-gravity direction) and vertical channels on the order of small to medium-sized venules and arteries when compared to micron-sized spheres. Furthermore, adhesion of nanospheres was not enhanced with pulsatility in flow. Overall, the presented data suggests that spheres 2–5 μm in size are optimal for targeting the wall in medium to large vessels relevant in several cardiovascular diseases.
Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery
Journal of Biomechanics
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres – but not nanospheres – from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review)
Molecular Membrane Biology
Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse blood hemodynamics and rheology, and the natural clearance process that tend to decrease the circulation time of foreign particles all lessen the probability of successful carrier interaction with the vascular wall. An effective vascular-targeted drug delivery system must be able to navigate through the bloodstream while avoiding immune clearance, attach to the vascular wall, and release its therapeutic cargo at the intended location. This review will summarize and analyze current literature reporting on (1) nanocarrier fabrication methods and materials that allow for optimum therapeutic encapsulation, protection, and release; (2) localization and binding dynamics of nanocarriers as influenced by hemodynamics and blood rheology in medium-to-large vessels; (3) blood cells' responses to various types of nanocarrier compositions and its effects on particle circulation time; and (4) properties that affect nanocarrier internalization at the target site.
Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels
Langmuir
Many variants of vascular-targeted carriers (VTCs) have been investigated for therapeutic intervention in several human diseases. However, in order to optimize the functionality of VTC in vivo, carriers’ physical properties, such as size and shape, are important considerations for a VTC design that evades the reticuloendothelial system (RES) and successfully interacts with the targeted vessel wall. Nonetheless, little evidence has been presented on the role of size in VTC’s interactions with the vascular wall, particularly in the microcirculation. Thus, in this work, we explore how particle size, along with hemodynamics (blood shear rate and vessel size) and hemorheology (blood hematocrit) affect the capacity for spheres to marginate (localize and adhere) to inflamed endothelium in a microfluidic model of human microvessels. Microspheres, particularly the 2 μm spheres, were found to show disproportionately higher margination than nanospheres in all hemodynamic conditions evaluated due to the poor ability of the latter to localize to the wall region from midstream. This work represents the first evidence that nanospheres may not exhibit “near wall excess” in microvessels, e.g., arterioles and venules, and therefore may not be suitable for imaging and drug delivery applications in cancer and other diseases affecting microvessels.
Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers
Biomaterials
Targeting of drug carriers to the vascular wall is of interest for localized delivery of therapeutics in many human diseases. Nanometer-sized spherical particles are widely proposed for use as carriers for vascular targeting, yet very little evidence has been presented as to their ability to interact with the vascular wall. Thus, this work focuses on elucidating the effect of particle size along with hemodynamics, blood rheology, and vessel size on the adhesion efficiency of targeted polymeric spheres to inflamed endothelium in vitro via parallel plate flow chamber assays. We find that the binding efficiency of spheres to the endothelium from blood flow generally increased with increasing particle size, wall shear rate and channel height for particle sizes from 100 nm up to 10 μm. However, nano-sized particles showed minimal adhesion to the endothelium from blood flow in horizontal (gravity or anti-gravity direction) and vertical channels on the order of small to medium-sized venules and arteries when compared to micron-sized spheres. Furthermore, adhesion of nanospheres was not enhanced with pulsatility in flow. Overall, the presented data suggests that spheres 2–5 μm in size are optimal for targeting the wall in medium to large vessels relevant in several cardiovascular diseases.
Targeting therapeutics to the vascular wall in atherosclerosis–Carrier size matters
Atherosclerosis
Objective Vascular-targeted imaging and drug delivery systems are promising for the treatment of atherosclerosis due to the vast involvement of endothelium in the initiation and growth of plaque. Herein, we investigated the role of particle size in dictating the ability of vascular-targeted spherical particles to interact with the vascular wall (VW) from pulsatile and recirculating human blood flow relevant in atherosclerosis. Methods In vitro parallel plate flow chambers (PPFC) with straight or vertical step channel were used to examine the localization and binding efficiency of inflammation-targeted polymeric spheres sized from 0.2 to 5 μm to inflamed endothelium from disturbed reconstituted and whole blood flow. Apolipoprotein deficient mice were used to study particle localization and binding to plaque in vivo. Results The efficiency of particle binding in disturbed reconstituted blood flow increases as spherical diameter increases from 500 nm to 5 μm. No significant difference was observed between adhesion of 200 nm and 500 nm spheres. Binding efficiency for all particle size was enhanced in disturbed whole blood flow except adhesion of 5 μm in pulsatile whole blood. The adhesion trend in the in vivo model confirmed the binding pattern observed in in vitro assays. Conclusions The presented data shows that the binding efficiency of vascular-targeted drug carriers in blood flow is a function of particle size, wall shear rate, flow type, blood composition and ligand characteristics. Overall, the presented results suggest that micron-sized spherical particles (2 μm), not nanospheres, are optimal for vascular-targeted drug delivery applications in medium to large vessel relevant in atherosclerosis.
Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery
Journal of Biomechanics
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres – but not nanospheres – from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review)
Molecular Membrane Biology
Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse blood hemodynamics and rheology, and the natural clearance process that tend to decrease the circulation time of foreign particles all lessen the probability of successful carrier interaction with the vascular wall. An effective vascular-targeted drug delivery system must be able to navigate through the bloodstream while avoiding immune clearance, attach to the vascular wall, and release its therapeutic cargo at the intended location. This review will summarize and analyze current literature reporting on (1) nanocarrier fabrication methods and materials that allow for optimum therapeutic encapsulation, protection, and release; (2) localization and binding dynamics of nanocarriers as influenced by hemodynamics and blood rheology in medium-to-large vessels; (3) blood cells' responses to various types of nanocarrier compositions and its effects on particle circulation time; and (4) properties that affect nanocarrier internalization at the target site.
Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels
Langmuir
Many variants of vascular-targeted carriers (VTCs) have been investigated for therapeutic intervention in several human diseases. However, in order to optimize the functionality of VTC in vivo, carriers’ physical properties, such as size and shape, are important considerations for a VTC design that evades the reticuloendothelial system (RES) and successfully interacts with the targeted vessel wall. Nonetheless, little evidence has been presented on the role of size in VTC’s interactions with the vascular wall, particularly in the microcirculation. Thus, in this work, we explore how particle size, along with hemodynamics (blood shear rate and vessel size) and hemorheology (blood hematocrit) affect the capacity for spheres to marginate (localize and adhere) to inflamed endothelium in a microfluidic model of human microvessels. Microspheres, particularly the 2 μm spheres, were found to show disproportionately higher margination than nanospheres in all hemodynamic conditions evaluated due to the poor ability of the latter to localize to the wall region from midstream. This work represents the first evidence that nanospheres may not exhibit “near wall excess” in microvessels, e.g., arterioles and venules, and therefore may not be suitable for imaging and drug delivery applications in cancer and other diseases affecting microvessels.
Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers
Biomaterials
Targeting of drug carriers to the vascular wall is of interest for localized delivery of therapeutics in many human diseases. Nanometer-sized spherical particles are widely proposed for use as carriers for vascular targeting, yet very little evidence has been presented as to their ability to interact with the vascular wall. Thus, this work focuses on elucidating the effect of particle size along with hemodynamics, blood rheology, and vessel size on the adhesion efficiency of targeted polymeric spheres to inflamed endothelium in vitro via parallel plate flow chamber assays. We find that the binding efficiency of spheres to the endothelium from blood flow generally increased with increasing particle size, wall shear rate and channel height for particle sizes from 100 nm up to 10 μm. However, nano-sized particles showed minimal adhesion to the endothelium from blood flow in horizontal (gravity or anti-gravity direction) and vertical channels on the order of small to medium-sized venules and arteries when compared to micron-sized spheres. Furthermore, adhesion of nanospheres was not enhanced with pulsatility in flow. Overall, the presented data suggests that spheres 2–5 μm in size are optimal for targeting the wall in medium to large vessels relevant in several cardiovascular diseases.
Targeting therapeutics to the vascular wall in atherosclerosis–Carrier size matters
Atherosclerosis
Objective Vascular-targeted imaging and drug delivery systems are promising for the treatment of atherosclerosis due to the vast involvement of endothelium in the initiation and growth of plaque. Herein, we investigated the role of particle size in dictating the ability of vascular-targeted spherical particles to interact with the vascular wall (VW) from pulsatile and recirculating human blood flow relevant in atherosclerosis. Methods In vitro parallel plate flow chambers (PPFC) with straight or vertical step channel were used to examine the localization and binding efficiency of inflammation-targeted polymeric spheres sized from 0.2 to 5 μm to inflamed endothelium from disturbed reconstituted and whole blood flow. Apolipoprotein deficient mice were used to study particle localization and binding to plaque in vivo. Results The efficiency of particle binding in disturbed reconstituted blood flow increases as spherical diameter increases from 500 nm to 5 μm. No significant difference was observed between adhesion of 200 nm and 500 nm spheres. Binding efficiency for all particle size was enhanced in disturbed whole blood flow except adhesion of 5 μm in pulsatile whole blood. The adhesion trend in the in vivo model confirmed the binding pattern observed in in vitro assays. Conclusions The presented data shows that the binding efficiency of vascular-targeted drug carriers in blood flow is a function of particle size, wall shear rate, flow type, blood composition and ligand characteristics. Overall, the presented results suggest that micron-sized spherical particles (2 μm), not nanospheres, are optimal for vascular-targeted drug delivery applications in medium to large vessel relevant in atherosclerosis.
Plasma Protein Corona Modulates the Vascular Wall Interaction of Drug Carriers in a Material and Donor Specific Manner
PloS one
The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid) (PLGA) spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer) is seen with ~60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases.
Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery
Journal of Biomechanics
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres – but not nanospheres – from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review)
Molecular Membrane Biology
Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse blood hemodynamics and rheology, and the natural clearance process that tend to decrease the circulation time of foreign particles all lessen the probability of successful carrier interaction with the vascular wall. An effective vascular-targeted drug delivery system must be able to navigate through the bloodstream while avoiding immune clearance, attach to the vascular wall, and release its therapeutic cargo at the intended location. This review will summarize and analyze current literature reporting on (1) nanocarrier fabrication methods and materials that allow for optimum therapeutic encapsulation, protection, and release; (2) localization and binding dynamics of nanocarriers as influenced by hemodynamics and blood rheology in medium-to-large vessels; (3) blood cells' responses to various types of nanocarrier compositions and its effects on particle circulation time; and (4) properties that affect nanocarrier internalization at the target site.
Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels
Langmuir
Many variants of vascular-targeted carriers (VTCs) have been investigated for therapeutic intervention in several human diseases. However, in order to optimize the functionality of VTC in vivo, carriers’ physical properties, such as size and shape, are important considerations for a VTC design that evades the reticuloendothelial system (RES) and successfully interacts with the targeted vessel wall. Nonetheless, little evidence has been presented on the role of size in VTC’s interactions with the vascular wall, particularly in the microcirculation. Thus, in this work, we explore how particle size, along with hemodynamics (blood shear rate and vessel size) and hemorheology (blood hematocrit) affect the capacity for spheres to marginate (localize and adhere) to inflamed endothelium in a microfluidic model of human microvessels. Microspheres, particularly the 2 μm spheres, were found to show disproportionately higher margination than nanospheres in all hemodynamic conditions evaluated due to the poor ability of the latter to localize to the wall region from midstream. This work represents the first evidence that nanospheres may not exhibit “near wall excess” in microvessels, e.g., arterioles and venules, and therefore may not be suitable for imaging and drug delivery applications in cancer and other diseases affecting microvessels.
Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers
Biomaterials
Targeting of drug carriers to the vascular wall is of interest for localized delivery of therapeutics in many human diseases. Nanometer-sized spherical particles are widely proposed for use as carriers for vascular targeting, yet very little evidence has been presented as to their ability to interact with the vascular wall. Thus, this work focuses on elucidating the effect of particle size along with hemodynamics, blood rheology, and vessel size on the adhesion efficiency of targeted polymeric spheres to inflamed endothelium in vitro via parallel plate flow chamber assays. We find that the binding efficiency of spheres to the endothelium from blood flow generally increased with increasing particle size, wall shear rate and channel height for particle sizes from 100 nm up to 10 μm. However, nano-sized particles showed minimal adhesion to the endothelium from blood flow in horizontal (gravity or anti-gravity direction) and vertical channels on the order of small to medium-sized venules and arteries when compared to micron-sized spheres. Furthermore, adhesion of nanospheres was not enhanced with pulsatility in flow. Overall, the presented data suggests that spheres 2–5 μm in size are optimal for targeting the wall in medium to large vessels relevant in several cardiovascular diseases.
Targeting therapeutics to the vascular wall in atherosclerosis–Carrier size matters
Atherosclerosis
Objective Vascular-targeted imaging and drug delivery systems are promising for the treatment of atherosclerosis due to the vast involvement of endothelium in the initiation and growth of plaque. Herein, we investigated the role of particle size in dictating the ability of vascular-targeted spherical particles to interact with the vascular wall (VW) from pulsatile and recirculating human blood flow relevant in atherosclerosis. Methods In vitro parallel plate flow chambers (PPFC) with straight or vertical step channel were used to examine the localization and binding efficiency of inflammation-targeted polymeric spheres sized from 0.2 to 5 μm to inflamed endothelium from disturbed reconstituted and whole blood flow. Apolipoprotein deficient mice were used to study particle localization and binding to plaque in vivo. Results The efficiency of particle binding in disturbed reconstituted blood flow increases as spherical diameter increases from 500 nm to 5 μm. No significant difference was observed between adhesion of 200 nm and 500 nm spheres. Binding efficiency for all particle size was enhanced in disturbed whole blood flow except adhesion of 5 μm in pulsatile whole blood. The adhesion trend in the in vivo model confirmed the binding pattern observed in in vitro assays. Conclusions The presented data shows that the binding efficiency of vascular-targeted drug carriers in blood flow is a function of particle size, wall shear rate, flow type, blood composition and ligand characteristics. Overall, the presented results suggest that micron-sized spherical particles (2 μm), not nanospheres, are optimal for vascular-targeted drug delivery applications in medium to large vessel relevant in atherosclerosis.
Plasma Protein Corona Modulates the Vascular Wall Interaction of Drug Carriers in a Material and Donor Specific Manner
PloS one
The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid) (PLGA) spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer) is seen with ~60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases.
Design and application of multifunctional DNA nanocarriers for therapeutic delivery
Acta Biomaterialia
The unique programmability of nucleic acids offers versatility and flexibility in the creation of self-assembled DNA nanostructures. To date, many three-dimensional DNA architectures of varying sizes and shapes have been precisely formed. Their biocompatibility, biodegradability and high intrinsic stability in physiological environments emphasize their emerging use as carriers for drug and gene delivery. Furthermore, DNA nanocarriers have been shown to enter cells efficiently and without the aid of transfection reagents. A key strength of DNA nanocarriers over other delivery systems is their modularity and their ability to control the spatial distribution of cargoes and ligands. Optimizing DNA nanocarrier properties to dictate their localization, uptake and intracellular trafficking is also possible. This review presents design considerations for DNA nanocarriers and examples of their use in the context of therapeutic delivery applications. The assembly of DNA nanocarriers and approaches for loading and releasing cargo are described. The stability and safety of DNA nanocarriers are also discussed, with particular attention to the in vivo physiological environment. Mechanisms of cellular uptake and intracellular trafficking are examined, and the paper concludes with strategies to enhance the delivery efficiency of DNA nanocarriers.
Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery
Journal of Biomechanics
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres – but not nanospheres – from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review)
Molecular Membrane Biology
Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse blood hemodynamics and rheology, and the natural clearance process that tend to decrease the circulation time of foreign particles all lessen the probability of successful carrier interaction with the vascular wall. An effective vascular-targeted drug delivery system must be able to navigate through the bloodstream while avoiding immune clearance, attach to the vascular wall, and release its therapeutic cargo at the intended location. This review will summarize and analyze current literature reporting on (1) nanocarrier fabrication methods and materials that allow for optimum therapeutic encapsulation, protection, and release; (2) localization and binding dynamics of nanocarriers as influenced by hemodynamics and blood rheology in medium-to-large vessels; (3) blood cells' responses to various types of nanocarrier compositions and its effects on particle circulation time; and (4) properties that affect nanocarrier internalization at the target site.
Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels
Langmuir
Many variants of vascular-targeted carriers (VTCs) have been investigated for therapeutic intervention in several human diseases. However, in order to optimize the functionality of VTC in vivo, carriers’ physical properties, such as size and shape, are important considerations for a VTC design that evades the reticuloendothelial system (RES) and successfully interacts with the targeted vessel wall. Nonetheless, little evidence has been presented on the role of size in VTC’s interactions with the vascular wall, particularly in the microcirculation. Thus, in this work, we explore how particle size, along with hemodynamics (blood shear rate and vessel size) and hemorheology (blood hematocrit) affect the capacity for spheres to marginate (localize and adhere) to inflamed endothelium in a microfluidic model of human microvessels. Microspheres, particularly the 2 μm spheres, were found to show disproportionately higher margination than nanospheres in all hemodynamic conditions evaluated due to the poor ability of the latter to localize to the wall region from midstream. This work represents the first evidence that nanospheres may not exhibit “near wall excess” in microvessels, e.g., arterioles and venules, and therefore may not be suitable for imaging and drug delivery applications in cancer and other diseases affecting microvessels.
Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers
Biomaterials
Targeting of drug carriers to the vascular wall is of interest for localized delivery of therapeutics in many human diseases. Nanometer-sized spherical particles are widely proposed for use as carriers for vascular targeting, yet very little evidence has been presented as to their ability to interact with the vascular wall. Thus, this work focuses on elucidating the effect of particle size along with hemodynamics, blood rheology, and vessel size on the adhesion efficiency of targeted polymeric spheres to inflamed endothelium in vitro via parallel plate flow chamber assays. We find that the binding efficiency of spheres to the endothelium from blood flow generally increased with increasing particle size, wall shear rate and channel height for particle sizes from 100 nm up to 10 μm. However, nano-sized particles showed minimal adhesion to the endothelium from blood flow in horizontal (gravity or anti-gravity direction) and vertical channels on the order of small to medium-sized venules and arteries when compared to micron-sized spheres. Furthermore, adhesion of nanospheres was not enhanced with pulsatility in flow. Overall, the presented data suggests that spheres 2–5 μm in size are optimal for targeting the wall in medium to large vessels relevant in several cardiovascular diseases.
Targeting therapeutics to the vascular wall in atherosclerosis–Carrier size matters
Atherosclerosis
Objective Vascular-targeted imaging and drug delivery systems are promising for the treatment of atherosclerosis due to the vast involvement of endothelium in the initiation and growth of plaque. Herein, we investigated the role of particle size in dictating the ability of vascular-targeted spherical particles to interact with the vascular wall (VW) from pulsatile and recirculating human blood flow relevant in atherosclerosis. Methods In vitro parallel plate flow chambers (PPFC) with straight or vertical step channel were used to examine the localization and binding efficiency of inflammation-targeted polymeric spheres sized from 0.2 to 5 μm to inflamed endothelium from disturbed reconstituted and whole blood flow. Apolipoprotein deficient mice were used to study particle localization and binding to plaque in vivo. Results The efficiency of particle binding in disturbed reconstituted blood flow increases as spherical diameter increases from 500 nm to 5 μm. No significant difference was observed between adhesion of 200 nm and 500 nm spheres. Binding efficiency for all particle size was enhanced in disturbed whole blood flow except adhesion of 5 μm in pulsatile whole blood. The adhesion trend in the in vivo model confirmed the binding pattern observed in in vitro assays. Conclusions The presented data shows that the binding efficiency of vascular-targeted drug carriers in blood flow is a function of particle size, wall shear rate, flow type, blood composition and ligand characteristics. Overall, the presented results suggest that micron-sized spherical particles (2 μm), not nanospheres, are optimal for vascular-targeted drug delivery applications in medium to large vessel relevant in atherosclerosis.
Plasma Protein Corona Modulates the Vascular Wall Interaction of Drug Carriers in a Material and Donor Specific Manner
PloS one
The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid) (PLGA) spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer) is seen with ~60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases.
Design and application of multifunctional DNA nanocarriers for therapeutic delivery
Acta Biomaterialia
The unique programmability of nucleic acids offers versatility and flexibility in the creation of self-assembled DNA nanostructures. To date, many three-dimensional DNA architectures of varying sizes and shapes have been precisely formed. Their biocompatibility, biodegradability and high intrinsic stability in physiological environments emphasize their emerging use as carriers for drug and gene delivery. Furthermore, DNA nanocarriers have been shown to enter cells efficiently and without the aid of transfection reagents. A key strength of DNA nanocarriers over other delivery systems is their modularity and their ability to control the spatial distribution of cargoes and ligands. Optimizing DNA nanocarrier properties to dictate their localization, uptake and intracellular trafficking is also possible. This review presents design considerations for DNA nanocarriers and examples of their use in the context of therapeutic delivery applications. The assembly of DNA nanocarriers and approaches for loading and releasing cargo are described. The stability and safety of DNA nanocarriers are also discussed, with particular attention to the in vivo physiological environment. Mechanisms of cellular uptake and intracellular trafficking are examined, and the paper concludes with strategies to enhance the delivery efficiency of DNA nanocarriers.
Aptamer-Targeted DNA Nanostructures for Therapeutic Delivery
Molecular Pharmaceutics
DNA-based nanostructures have been widely used in various applications due to their structural diversity, programmability, and uniform structures. Their intrinsic biocompatibility and biodegradability further motivates the investigation of DNA-based nanostructures as delivery vehicles. Incorporating AS1411 aptamers into DNA pyramids leads to enhanced intracellular uptake and selectively inhibits the growth of cancer cells, achieved without the use of transfection reagents. Furthermore, aptamer-displaying pyramids are found to be substantially more resistant to nuclease degradation than single-stranded aptamers. These findings, along with their modularity, reinforce the potential of DNA-based nanostructures for therapeutic applications.
Possible Matching Profiles
The following profiles may or may not be the same professor:
- Phapanin Charoenphol (80% Match)
Research Assistant Professor
Texas A&M University - Texas A&m University
