Delivery of multipurpose prevention drug combinations from electrospun nanofibers using composite microarchitectures

Abstract

Background Electrospun drug-eluting fabrics have enormous potential for the delivery of physicochemically diverse drugs in combination by controlling the underlying material chemistry and fabric microarchitecture. However, the rationale for formulating drugs at high drug loading in the same or separate fibers is unknown but has important implications for product development and clinical applications. Methods Using a production-scale free-surface electrospinning instrument, we produced electrospun nanofibers with different microscale geometries for the co-delivery of tenofovir (TFV) and levonorgestrel (LNG) – two lead drug candidates for multipurpose prevention of HIV acquisition and unintended pregnancy. We investigated the in vitro drug release of TFV and LNG combinations from composites that deliver the two drugs from the same fiber (combined fibers) or from separate fibers in a stacked or interwoven architecture. For stacked composites, we also examined the role that fabric thickness has on drug-release kinetics. We also measured the cytotoxicity and antiviral activity of the drugs delivered alone and in combination. Results Herein, we report on the solution and processing parameters for the free-surface electrospinning of medical fabrics with controlled microarchitecture and high drug loading (up to 20 wt%). We observed that in vitro release of the highly water-soluble TFV, but not the water-insoluble LNG, was affected by composite microarchitecture, fabric thickness, and drug content. Finally, we showed that the drug-loaded nanofibers are noncytotoxic and that the antiviral activity of TFV is preserved through the electrospinning process and when combined with LNG. Conclusion Electrospun fabrics with high drug loading create multicomponent systems that benefit from the independent control of the nanofibrous microarchitecture. Our findings are significant because they will inform the design and production of composite electrospun fabrics for the co-delivery of physicochemically diverse drugs that may be useful for multipurpose prevention.

Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold To Prevent HIV Infection

“…Additionally, EFs have the potential to simultaneously deliver incorporated compounds, including biologics, such as proteins and oligonucleotides (89)(90)(91), as well as traditional antiviral drugs (92)(93)(94), making polymeric EFs an attractive platform for the delivery of multipurpose drugs with activity against STIs. Although EFs are still being explored to establish their safety and efficacy in vitro and in vivo, current in vitro studies indicate strong safety and efficacy profiles (35,36,40,85,86).…”

In Pursuit of Functional Electrospun Materials for Clinical Applications in Humans

“…Advantages of free surface technology emerge from avoiding needle clogging issues and avoiding nozzle-nozzle interactions since jets emanating from a free surface will achieve self-optimize spacing based on applied voltage and solution properties. Free surface designs may also allow for scale-up of nanofibers containing particles or fiber mats fabricated with distinct microarchitectures for drugdelivery applications [101,102]. Although both free surface and multi-nozzle designs have their advantages, it seems the industrial landscape has become more focused on free surface designs because of the increased compatibility with manufacturing.…”

Polymer-based nanocarriers for vaginal drug delivery

“…The mesh created by fibers could also physically block sperm penetration thus providing an additional contraceptive mechanism [130]. In a following report, the same group developed PVA nanofibers for the co-delivery of tenofovir and levonorgestrel (a contraceptive progestin) using a production scale electrospinner [131]. Fabrics with fibers presenting diameters around 200-300 nm and different composite microarchitectures were obtained, and shown to possess good drug association efficiencies (typically above 80% in weight) and reasonably high drug loading (up to around 14% and 17% in weight for tenofovir and levonorgestrel, respectively).…”