Nanoparticle-releasing nanofiber composites for enhanced in vivo vaginal retention

Abstract

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 nanoparticles that diffuse quickly through mucus. We hypothesized that this novel dual-functioning (mucoadhesive/mucus–penetrating) composite material would provide enhanced retention of nanoparticles 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 24h 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 nanoparticles in the reproductive tract at 24h compared to aqueous suspensions. Compared to nanoparticles in aqueous suspension, the nanoparticles in fiber composites exhibited sustained and higher etravirine concentrations after 24h 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.

Recent advances in the mucus-interacting approach for vaginal drug delivery: from mucoadhesive to mucus-penetrating nanoparticles

“…More recently, Krogstad et al [32] designed NP-releasing NF composites for enhanced in vivo vaginal retention. In particular, NFs consisted of two mucoadhesive polymers, such as PVA and PVP, and were loaded with the mucus-penetrating PEGylated PLGA NPs.…”

Pharmaceutical Vehicles for Vaginal and Rectal Administration of Anti-HIV Microbicide Nanosystems

“…The concept is quite recent but available studies suggest great potential. Krogstad et al [120] first proposed the use of two types of nanofibers, based either on PVA (≈250 nm cross-section diameter) or PVP (≈300 nm cross-section diameter), two mucoadhesive polymers, for the incorporation of PLGA-based NPs (≈170–180 nm). Composite nanofiber mats were rapidly wetted and disintegrated within a few seconds when exposed to an aqueous environment.…”

Electrospinning of carboxymethyl starch/poly(L‐lactide acid) composite nanofiber

“…The existing repulsive force also reduces the fiber diameter during the electrospinning. In biomedical and tissue engineering field, nanofibers produced by electrospinning were obtained by multiple combinations of the polymer including a natural polymer …”

“…In biomedical and tissue engineering field, nanofibers produced by electrospinning were obtained by multiple combinations of the polymer including a natural polymer. [11][12][13] Various natural polymers have been used to incorporate with synthetic polymers. 14,15 The natural polymer provides a good cell attraction and provides a platform for cells to proliferate and differentiate.…”