title: A nanoscale drug-entrapment strategy for hydrogel-based systems for the delivery of poorly soluble drugs.
abstract: The hydrophilic nature of hydrogel matrices makes them disadvantageous to entrap poorly soluble therapeutic agents and greatly restricts their applications as drug-delivery systems. In this study, we demonstrated that sustained delivery of lipophilic drugs in hydrogel-based devices can be readily achieved by enhancing retention of drugs within micelles. This nanoscale drug-entrapment strategy was applied to develop a polymeric drug-eluting stent. Sirolimus, a lipophilic anti-proliferative/immunosuppressive drug, was entrapped into the hydrophobic core of Pluronic L121 micelles and then blended in a chitosan-based strip and crosslinked by an epoxy compound to fabricate test stents. It was found that the use of such a nanoscale drug-entrapment strategy was able to significantly increase the loading efficiency of lipophilic drugs, prevent the drug from aggregation and beneficially reduce its initial burst release; thus, the duration of drug release was extended considerably. When implanting the stent in rabbit infrarenal abdominal aortas, in-stent restenosis was markedly reduced and less inflammatory reaction was observed, while unfavorable effects such as delayed endothelial healing caused by the overdose of sirolimus could be significantly evaded.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Chen
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Tsai
authors.forename: Chin-Tang
authors.initials: CT
authors.lastname: Liu
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Peng
authors.forename: Wei-Yun
authors.initials: WY
authors.lastname: Lai
authors.forename: Shiang-Jiuun
authors.initials: SJ
authors.lastname: Chen
authors.forename: Yen
authors.initials: Y
authors.lastname: Chang
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D054855:Drug-Eluting Stents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000737:chemistry; D008823:Micelles; D011817:Rabbits; D051381:Rats
chemical_list: D007166:Immunosuppressive Agents; D008823:Micelles; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan