Rapidly Biodegrading PLGA-Polyurethane Fibers for Sustained Release of Physicochemically Diverse Drugs.

Autor:	Blakney AK; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, Washington 98195, United States., Simonovsky FI; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, Washington 98195, United States., Suydam IT; Department of Chemistry, Seattle University, 901 12th Ave., Seattle, Washington 98122, United States., Ratner BD; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, Washington 98195, United States.; Department of Chemical Engineering, University of Washington, 3720 15th Ave NE, Seattle, Washington 98195, United States., Woodrow KA; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, Washington 98195, United States.
Jazyk:	angličtina
Zdroj:	ACS biomaterials science & engineering [ACS Biomater Sci Eng] 2016 Sep 12; Vol. 2 (9), pp. 1595-1607. Date of Electronic Publication: 2016 Jul 13.
DOI:	10.1021/acsbiomaterials.6b00346
Abstrakt:	Sustained release of physicochemically diverse drugs from electrospun fibers remains a challenge and precludes the use of fibers in many medical applications. Here, we synthesize a new class of polyurethanes with poly(lactic-co-glycolic acid) (PLGA) moieties that degrade faster than polyurethanes based on polycaprolactone. The new polymers, with varying hard to soft segment ratios and fluorobenzene pendant group content, were electrospun into nanofibers and loaded with four physicochemically diverse small molecule drugs. Polymers were characterized using GPC, XPS, and 19 F NMR. The size and morphology of electrospun fibers were visualized using SEM, and drug/polymer compatibility and drug crystallinity were evaluated using DSC. We measured in vitro drug release, polymer degradation and cell-culture cytotoxicity of biodegradation products. We show that these newly synthesized PLGA-based polyurethanes degrade up to 65-80% within 4 weeks and are cytocompatible in vitro . The drug-loaded electrospun fibers were amorphous solid dispersions. We found that increasing the hard to soft segment ratio of the polymer enhances the sustained release of positively charged drugs, whereas increasing the fluorobenzene pendant content caused more rapid release of some drugs. In summary, increasing the hard segment or fluorobenzene pendant content of segmented polyurethanes containing PLGA moieties allows for modulation of physicochemically diverse drug release from electrospun fibers while maintaining a biologically relevant biodegradation rate. Competing Interests: The authors declare no competing financial interest.
Databáze:	MEDLINE
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