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.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Chen MC,Tsai HW,Liu CT,Peng SF,Lai WY,Chen SJ,Chang Y,Sung HW

doi

10.1016/j.biomaterials.2008.12.047

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

2102-11

issue

11

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(08)01049-1

journal_volume

30

pub_type

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