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Adv Healthc Mater. 2014 Apr 7. doi: 10.1002/adhm.201300676. [Epub ahead of print]

Planar Microdevices for Enhanced In Vivo Retention and Oral Bioavailability of Poorly Permeable Drugs.

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  • 1Department of Bioengineering and Therapeutic Sciences, University of California, 1700 4th Street, Byers Hall 204, Box 2520, San Francisco, CA, 94158, USA.

Abstract

The development of novel oral drug delivery platforms for administering therapeutics in a safe and effective manner through the harsh gastrointestinal environment is of great importance. Here, the use of engineered thin planar poly(methyl methacrylate) (PMMA) microdevices is tested to enhance oral bioavailability of acyclovir, a poorly permeable drug. Acyclovir is loaded into the unidirectional drug releasing microdevice reservoirs using a drug entrapping photocross-linkable hydrogel matrix. An increase in acyclovir permeation across in vitro caco-2 monolayer is seen in the presence of microdevices as compared with acyclovir-entrapped hydrogels or free acyclovir solution. Cell proliferation studies show that microdevices are relatively nontoxic in nature for use in in vivo studies. Enhanced in vivo retention of microdevices is observed as their thin side walls experience minimal peristaltic shear stress as compared with spherical microparticles. Unidirectional acyclovir release and enhanced retention of microdevices achieve a 4.5-fold increase in bioavailability in vivo as compared with an oral gavage of acyclovir solution with the same drug mass. The enhanced oral bioavailability results suggest that thin, planar, bioadhesive, and unidirectional drug releasing microdevices will significantly improve the systemic and localized delivery of a broad range of oral therapeutics in the near future.

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

acyclovir; oral bioavailability; oral drug delivery; planar microdevices; retention

PMID:
24711341
[PubMed - as supplied by publisher]
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