Electrospun fibers for vaginal anti-HIV drug delivery

Blakney, Anna K.; Ball, Christopher; Krogstad, Emily; Woodrow, Kim A.

doi:10.1016/j.antiviral.2013.09.022

Cited by 84 publications

(54 citation statements)

References 46 publications

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“…Increased drug loading did not reduce productivity, and we observed high material efficiency (88 to 94% for PVP materials) resulting in a fiber production rate of ϳ7 mg/min using a benchtop instrument with a single nozzle. We recently reviewed the scale-up potential and expected cost of electrospun microbicides, finding that current electrospinning technologies are capable of producing up to 6.5 kg of fiber every hour (10 to 20 million doses annually), at a projected cost of $0.50 to $3.00 per dose depending upon a large number of factors such as initial investments in capital, material costs, and production volume (39).…”

Section: Discussionmentioning

confidence: 99%

Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV

Ball

Woodrow

2014

Antimicrob Agents Chemother

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The development of topical anti-human immunodeficiency virus (HIV) microbicides may provide women with strategies to protect themselves against sexual HIV transmission. Pericoital drug delivery systems intended for use immediately before sex, such as microbicide gels, must deliver high drug doses for maximal effectiveness. The goal of achieving a high antiretroviral dose is complicated by the need to simultaneously retain the dose and quickly release drug compounds into the tissue. For drugs with limited solubility in vaginal gels, increasing the gel volume to increase the dose can result in leakage. While solid dosage forms like films and tablets increase retention, they often require more than 15 min to fully dissolve, potentially increasing the risk of inducing epithelial abrasions during sex. Here, we demonstrate that water-soluble electrospun fibers, with their high surface area-to-volume ratio and ability to disperse antiretrovirals, can serve as an alternative solid dosage form for microbicides requiring both high drug loading and rapid hydration. We formulated maraviroc at up to 28 wt% into electrospun solid dispersions made from either polyvinylpyrrolidone or poly(ethylene oxide) nanofibers or microfibers and investigated the role of drug loading, distribution, and crystallinity in determining drug release rates into aqueous media. We show here that water-soluble electrospun materials can rapidly release maraviroc upon contact with moisture and that drug delivery is faster (less than 6 min under sink conditions) when maraviroc is electrospun in polyvinylpyrrolidone fibers containing an excipient wetting agent. These materials offer an alternative dosage form to current pericoital microbicides.

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Section: Discussionmentioning

confidence: 99%

Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV

Ball

Woodrow

2014

Antimicrob Agents Chemother

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“…As an example, Ham et al [88] proposed Polymeric fibers with diameters in the nano-range are attracting a great deal of attention in the field of vaginal microbicide formulation, particularly due to their versatility for multi-drug loading and release, and physical properties (e.g., increased surface area, good mechanical resistance, and enhanced distribution at mucosal surfaces) [127]. A few significant examples have been so far described.…”

Section: Accepted Manuscriptmentioning

confidence: 98%

Polymer-based nanocarriers for vaginal drug delivery

Neves

Nunes

Machado

et al. 2015

Advanced Drug Delivery Reviews

114

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The vaginal delivery of various drugs is well described and its relevance established in current medical practice. Alongside recent advances and achievements in the fields of pharmaceutical nanotechnology and nanomedicine, there is an increasing interest in the potential use of different nanocarriers for the delivery of old and new pharmacologically active molecules with either therapeutic or prophylactic purposes. Nanosystems of polymeric nature in particular have been investigated over the last years and their interactions with mucosal fluids and tissues, as well as genital tract biodistribution upon vaginal administration, are now better understood. While different applications have been envisioned, most of the current research is focusing in the development of nano-formulations with the potential to inhibit the vaginal transmission of HIV upon sexual intercourse. The present work focuses its discussion on the potential and perils of polymer-based nanocarriers for the vaginal administration of different pharmacologically active molecules.

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“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Grooms

Vuong

Tyo

et al. 2016

Antimicrob Agents Chemother

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Despite current prophylactic strategies, sexually transmitted infections (STIs) remain significant contributors to global health challenges, spurring the development of new multipurpose delivery technologies to protect individuals from and treat virus infections. However, there are few methods currently available to prevent and no method to date that cures human immunodeficiency virus (HIV) infection or combinations of STIs. While current oral and topical preexposure prophylaxes have protected against HIV infection, they have primarily relied on antiretrovirals (ARVs) to inhibit infection. Yet continued challenges with ARVs include user adherence to daily treatment regimens and the potential toxicity and antiviral resistance associated with chronic use. The integration of new biological agents may avert some of these adverse effects while also providing new mechanisms to prevent infection. Of the biologic-based antivirals, griffithsin (GRFT) has demonstrated potent inhibition of HIV-1 (and a multitude of other viruses) by adhering to and inactivating HIV-1 immediately upon contact. In parallel with the development of GRFT, electrospun fibers (EFs) have emerged as a promising platform for the delivery of agents active against HIV infection. In the study described here, our goal was to extend the mechanistic diversity of active agents and electrospun fibers by incorporating the biologic GRFT on the EF surface rather than within the EFs to inactivate HIV prior to cellular entry. We fabricated and characterized GRFT-modified EFs (GRFT-EFs) with different surface modification densities of GRFT and demonstrated their safety and efficacy against HIV-1 infection in vitro. We believe that EFs are a unique platform that may be enhanced by incorporation of additional antiviral agents to prevent STIs via multiple mechanisms. N ewly acquired sexually transmitted infections (STIs) affect 340 million people per year (1-3) and exert a significant impact on global health. Human immunodeficiency virus type 1 (HIV-1) affects ϳ35 million people globally (2-5), while untreated STIs, such as those caused by herpes simplex virus 2 (HSV-2), can enhance both the acquisition and the transmission of HIV and other agents of STIs by 2-to 4-fold (6, 7). In light of the findings of recent clinical trials, a specific, multipurpose prevention technology that has the ability to prevent multiple STIs using one delivery platform and that also increases user adherence urgently needs to be developed (8-18). In the study described here, we sought to shift current topical preexposure prophylaxis (PrEP) paradigms by integrating a multipurpose biological delivery approach to debilitate and inactivate HIV.Our long-term goal is to develop a multipurpose biologically inspired electrospun fiber (EF) prevention technology that takes cues from the innate microenvironment of the female reproductive tract to more strategically narrow the gaps in microbicide efficacy. In this work, we evaluated the potential of polymeric EF scaffolds surface modified with the po...

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Electrospun fibers for vaginal anti-HIV drug delivery

Cited by 84 publications

References 46 publications

Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV

Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV

Polymer-based nanocarriers for vaginal drug delivery

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

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