A nanoscale drug-entrapment strategy for hydrogel-based systems for the delivery of poorly soluble drugs.
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.
Chen
Mei-Chin
MC
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Tsai
Hung-Wen
HW
Liu
Chin-Tang
CT
Peng
Shu-Fen
SF
Lai
Wei-Yun
WY
Chen
Shiang-Jiuun
SJ
Chang
Yen
Y
Sung
Hsing-Wen
HW
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
D007166:Immunosuppressive Agents; D008823:Micelles; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan