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Multimechanistic Polymer Based Novel Drug Eluting Stent Coating
Project Description :

Background: stent thrombosis (st) and delayed re-endothelialisation pose to be the major problems associated with currently available drug eluting stents (des). anti-restenotic drug which prevent vascular smooth muscle cell (vsmc) proliferation without delaying re- endothelialisation, controlled drug release carrier system and non-thrombogenic polymeric matrix are needed to combat the problems mentioned above. biochanin a is an isoflavone phytoestrogen which was reported to be anti-proliferative, vasculoprotective, anti-inflammatory and anti-oxidant. thedrug has not been reported for stent application earlier. it may prevent vsmc proliferation without delaying re-endothelializtion. ldh is a new carrier system meant for anionic drugs with high drug loading efficiency and reported to show stable release kinetics. polylactic acid is the most widely used polymer in stent systems. but it is brittle and hydrophobic as such. hydrophilic surfaces resist protein adhesion. pla is copolymerized with peg, as peg grafted surfaces are well proven to be hydrophilic and haemocompatible. heparin is tagged to pla-peg copolymer to further make it non-thrombogenic and enhance re-endothelialisation objective: to develop a des surface coating with biochanin a which is loaded in layer double hydroxide(ldh) nanoparticles and further encapsulated in heparin-tagged pla-peg (polylactic acid –co- polyethyleneglycol) copolymer. methodology: (mg/al) ldh nanoparticles are synthesized by co-precipitation method. characterized by ftir, xrd, tem, zetasizer. biochanin a was loaded in ldh by ion-exchange method as well as insitu loading with simultaneous synthesis of ldh. stability studies were carried out for 7 weeks with aqueous suspension. drug release studies have been performed and amount of drug released is estimated by uv-spectrophotometry. pla-peg copolymer was synthesized by trans-esterification reaction and, acylation and esterification reaction. polymer was then covalently attached to heparin by using dcc (dicyclohexyl carbodiimide) and dmap (dimethylaminopyridine). it was characterized by ftir, dsc, gpc. biochanin a loaded ldh nanoparticles were encapsulated in heparin tagged pla-peg copolymer by solvent evaporation technique using chloroform as the solvent. the final formulation has been tested for in vitro degradability, hemocompatibility, hydrophilicity, protein adhesion, dsc analysis. results: ldh nanoparticles have been successfully synthesized. significant drug loading (63%) has been observed in ldh nanoparticles synthesized with insitu loading with a desirable controlled drug release profile up to 16 days. 44% drug loading and a release profile of 9 days has been observed with drug loaded by ion exchange method. complete degradation of pla-peg copolymer has been observed at around 90 days. nano-encapsulation of bca-ldh has been successfully done for the final stent coating. % hemolysis of all the samples tested have been found to be lessthan 2%, so non-hemolytic. contact angle of pla was decreased from 92 to 71 after copolymerization with peg. protein adsorbed on 1sq cm film of pla-peg copolymer was 0.052mg when compared to pla alone (0.292mg). conclusion: the developed stent surface coating is non-thrombogenic, anti-fouling and sufficiently hydrophilic and releases the drug at a controlled manner with a desirable polymer degradation profile. therefore, it can be concluded that, the developed stent surface coating offers non-thrombogenecity, may prevent restenosis without delaying re-endothelialisation. hence, the developed stent surface coating is superior to the existing formulation coatings.

 
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Project Details :
  • Date : Jan 31,2016
  • Innovator : Ms. Shiva Kalyani Adepu
  • Guide Name : Dr Govinda Kapusetti And Prof. Kiran Kalia
  • College : National Institute of Pharmaceutical Education and Research(NIPER)-Ahmedabad
  • Submission Year : 2016
  • Category : Biomedical Engineering
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