Journal
BIOMATERIALS
Volume 144, Issue -, Pages 1-16Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.07.034
Keywords
Nanoparticles; Nanofibers; Vaginal drug delivery; Microbicides; Electrospinning; Pharmacokinetics
Funding
- NIH [AI094412, AI112002, UM1 AI-120176, AI-077390, AI-077390-S1, AI-077390-S2, AI-077390-S3, 1UL1-RR025014, P510D010425]
- University of Washington STD/AIDS Training Fellowship [NIH T32 AI07140]
- SURP Space Grant Program 6 [ecG1 A68796]
- Milo Gibaldi endowment
- NIH T032 Pharmacological Sciences Training Grant [T32-GM007750]
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Current approaches for topical vaginal administration of nanoparticles result in poor retention and extensive leakage. To overcome these challenges, we developed a nanoparticle-releasing nanofiber delivery platform and evaluated its ability to improve nanoparticle retention in a murine model. We individually tailored two components of this drug delivery system for optimal interaction with mucus, designing (1) mucoadhesive fibers for better retention in the vaginal tract, and (2) PEGylated nano particles that diffuse quickly through mucus. We hypothesized that this novel dual -functioning (mucoadhesive/mucus penetrating) composite material would provide enhanced retention of nano particles in the vaginal mucosa. Equivalent doses of fluorescent nanoparticles were vaginally administered to mice in either water (aqueous suspension) or fiber composites, and fluorescent content was quantified in cervicovaginal mucus and vaginal tissue at time points from 24 h to 7d. We also fabricated composite fibers containing etravirine-loaded nanoparticles and evaluated the pharmacokinetics over 7d. We found that our composite materials provided approximately 30 -fold greater retention of nano particles in the reproductive tract at 24 h compared to aqueous suspensions. Compared to nanoparticles in aqueous suspension, the nanoparticles in fiber composites exhibited sustained and higher etravirine concentrations after 24 h and up to 7d, demonstrating the capabilities of this new delivery platform to sustain nanoparticle release out to 3d and drug retention out to one week after a single administration. This is the first report of nanoparticle-releasing fibers for vaginal drug delivery, as well as the first study of a single delivery system that combines two components uniquely engineered for complementary interactions with mucus. (C) 2017 Elsevier Ltd. All rights reserved.
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