Minimally invasive endovascular embolization procedures decrease surgery time, speed up recovery, and provide the possibility for more comprehensive treatment of aneurysms, arteriovenous malformations (AVMs), and hypervascular tumors. Liquid embolic agents (LEAs) are preferred over mechanical embolic agents, such as coils, because they achieve homogeneous filling of aneurysms and more complex…
Minimally invasive endovascular embolization procedures decrease surgery time, speed up recovery, and provide the possibility for more comprehensive treatment of aneurysms, arteriovenous malformations (AVMs), and hypervascular tumors. Liquid embolic agents (LEAs) are preferred over mechanical embolic agents, such as coils, because they achieve homogeneous filling of aneurysms and more complex angioarchitectures. The gold standard of commercially available LEAs is dissolved in dimethyl sulfoxide (DMSO), which has been associated with vasospasm and angiotoxicity. The aim of this study was to investigate amino acid substitution in an enzyme-degradable side group of an N-isopropylacrylamide (NIPAAm) copolymer for the development of a LEA that would be delivered in water and degrade at the rate that tissue is regenerated. NIPAAm copolymers have a lower critical solution temperature (LCST) due to their amphiphilic nature. This property enables them to be delivered as liquids through a microcatheter below their LCST and to solidify in situ above the LCST, which would result in the successful selective occlusion of blood vessels. Therefore, in this work, a series of poly(NIPAAm-co-peptide) copolymers with hydrophobic side groups containing the Ala-Pro-Gly-Leu collagenase substrate peptide sequence were synthesized as in situ forming, injectable copolymers.. The Gly-Leu peptide bond in these polypeptides is cleaved by collagenase, converting the side group into the more hydrophilic Gly-Ala-Pro-Gly-COOH (GAPG-COOH), thus increasing the LCST of the hydrogel after enzyme degradation. Enzyme degradation property and moderate mechanical stability convinces the use of these copolymers as liquid embolic agents.
Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo…
Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo from the bodily environment, and reduction in systemic side effects. This experiment used a single emulsion technique to encapsulate L-tyrosine in PLGA microparticles and UV spectrophotometry to analyze the drug release over a period of one week. The release assay found that for the tested samples, the released amount is distinct initially, but is about the same after 4 days, and they generally follow the same normalized percent released pattern. The experiment could continue with testing more samples, test the same samples for a longer duration, and look into higher w/w concentrations such as 20% or 50%.
In an embolization therapy, a material is injected into a vessel to block blood flow. While this therapy is useful in starving cancerous cells it can be dangerous, with some blockades in the brain dislodging and causing strokes or blindness. Currently, embolic materials on the market such as metal coils,…
In an embolization therapy, a material is injected into a vessel to block blood flow. While this therapy is useful in starving cancerous cells it can be dangerous, with some blockades in the brain dislodging and causing strokes or blindness. Currently, embolic materials on the market such as metal coils, balloons, and liquid embolic agents do not have a quick removal procedure. An ultrasound cleavable material could be removed in an emergency situation without invasive surgery. The primary goal of this research is to design and synthesize a polymer that can be broken down by high intensity focused ultrasound (HIFU). Initially, we have tested the ultrasound sensitive qualities on PPODA-QT hydrogel, a common embolic agent, but the gel showed no physical change after HIFU exposure. It is theorized that PNIPAAm combined with HIFU sensitive monomers can develop a temperature and ultrasound sensitive embolic agent. In our studies, poly(NIPAAm-co-tBa) had a slight lower critical solution temperature (LCST) change of about 2˚C from before to after HIFU while the study with poly(NIPAAm-co-ACL-BME) and PPODA-QT showed no change in LCST.
