期刊
PHARMACEUTICAL RESEARCH
卷 33, 期 1, 页码 125-136出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-015-1769-0
关键词
electrospinning; high loading; HIV; programmable release; tenofovir
资金
- Bill and Melinda Gates Foundation [OPP11110945]
- National Institutes of Health [AI098648, AI112002]
Sustained release of small molecule hydrophilic drugs at high doses remains difficult to achieve from electrospun fibers and limits their use in clinical applications. Here we investigate tunable release of several water-soluble anti-HIV drugs from electrospun fibers fabricated with blends of two biodegradable polyesters. Drug-loaded fibers were fabricated by electrospinning ratios of PCL and PLGA. Fiber morphology was imaged by SEM, and DSC was used to measure thermal properties. HPLC was used to measure drug loading and release from fibers. Cytotoxicity and antiviral activity of drug-loaded fibers were measured in an in vitro cell culture assay. We show programmable release of hydrophilic antiretroviral drugs loaded up to 40 wt%. Incremental tuning of highly-loaded drug fibers within 24 h or > 30 days was achieved by controlling the ratio of PCL and PLGA. Fiber compositions containing higher PCL content yielded greater burst release whereas fibers with higher PLGA content resulted in greater sustained release kinetics. We also demonstrated that our drug-loaded fibers are safe and can sustain inhibition of HIV in vitro. These data suggest that we were able to overcome current limitations associated with sustained release of small molecule hydrophilic drugs at clinically relevant doses. We expect that our system represents an effective strategy to sustain delivery of water-soluble molecules that will benefit a variety of biomedical applications.
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