ReviewElectrospun bers for vaginal anti-HIV drug deliveryAnna K. Blakney, Cameron Ball, Emily A. Krogstad, Kim A. WoodrowDepartment of Bioengineering, University of Washington, Seattle, Washington, United Statesarti cle i nfoArticle history:Received 21 June 2013Revised 19 September 2013Accepted 26 September 2013Available online 1 November 2013Keywords:Human immunodeciency virusMicrobicideVaginal deliveryElectrospun bersAntiretroviralabstractDiversity of microbicide delivery systems is essential for future success in the prevention and treatmentof HIV in order to account for the varied populations of women all over the world that may benet fromuse of these products. Recently, a novel dosage form for intravaginal drug delivery has been developedusing drug-elutingbers fabricated by electrospinning. There is a strong rationale to support the ideathatdrug-elutingberscanbedesignedtorealizemultipledesignconstraintsinasingleproductfortopicalHIVprevention:bersareabletodeliverawiderangeofagents, incorporatemultipleagentsvia composites, and facilitate controlled release over relevant time frames for pericoital and sustained(coitally-independent) use. It is also technologically feasible to scale-up production of ber-based micro-bicides. Electrospun bers may allow for prioritization of physical attributes that affect user perceptionswithout compromising biological efcacy. Challenges with using bers as a microbicide include issuesrelated to vehicle deployment, spreading and retention in the vaginal vault. In addition, studies will needto address the interaction of the bers with the mucosal environment, including unknown safety and tox-icity. Sustained release ber microbicides capable of delivering multiple antiretroviral drugs while simul-taneouslyexhibitingtunabledegradationor dissolutionof thebers is alsoachallenge. However,electrospunbersareapromisingnewplatformfor vaginal deliveryof anti-HIVagentsandfutureresearch will inform their place in the eld. This article is based on a presentation at the Product Devel-opment Workshop 2013: HIV and Multipurpose Prevention Technologies, held in Arlington, Virginia onFebruary 2021, 2013. It forms part of a special supplement to Antiviral Research. 2013 Elsevier B.V. All rights reserved.Contents1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S92. Electrospun fibers for drug delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S102.1. Breadth of API delivery using electrospun fibers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S112.2. Rapid and sustained release from drug-eluting fibers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S122.3. Challenges in electrospun fibers for vaginal delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S133. Scale-up of electrospun fibers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S133.1. Materials and capital investments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S133.2. Manufacturing capability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S133.3. Scale-up equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S144. Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S14References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S151. IntroductionTopical microbicides are a critical component of the preventionportfolio to combat sexual transmission of HIV. One of the priori-ties in the eld is to confront the low levels of user adherence thathave been documented in clinical trials of microbicides. The earlyterminationof VOICEduetolowuser adherencecompromisedevaluation of efcacy (Marrazzo et al., 2013). Vaginal drug deliverysystems (DDS) play a principle role in bridging biological efcacyand behavioral adherence, which collectively determine the overallimpact of a topical microbicide product. It is unlikely that a singleDDStechnologywill solvethepreventionneedsforall women,0166-3542/$ - see front matter 2013 Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.antiviral.2013.09.022Corresponding author. Address: Box 355061, 3720 15th Avenue NE, Seattle, WA98195, United States. Tel.: +1 (206) 685 6831.E-mail address: woodrow@uw.edu (K.A. Woodrow).Antiviral Research 100 (2013) S9S16ContentslistsavailableatScienceDirectAntiviral Researchj our nal homepage: www. el sevi er . com/ l ocat e/ ant i vi r alparticularly for adolescent women in low-resource settings wherethe crises of womens reproductive health is complicated by issuesof poverty, malnutrition, pooreducation, andgenderinequality.Forthisreason, theportfolioofavailablemicrobicideDDSneedsto be numerous and diverse.TheadvancementanddevelopmentofanysinglemicrobicideDDS must prioritize the capacity of the DDS to design for physicalattributes that impact user perceptions without compromising thedesign for biological efcacy. The ultimate decision to use a micro-bicide product is inuenced by a complex combination of productattributes(sensoryperceptions, dosingfrequency, coital associa-tion), userdemographics(age, race, culture), andperceivedrisksfor HIV as well as perceived benets from product use. These userperceptions are the rst barrier to designing effective microbicideproducts, but are often the last consideration in product develop-ment. In addition to beingacceptable tousers,theproduct mustdeliver bioactive compounds, possibly in combination, over a rele-vant period of time (both coitally dependent and independent), beaffordable, and have the ability to be manufactured on a produc-tion scale. Future development of products will likely incorporatedesign iterations informed by user perception as well as biologicalefcacy.A number of microbicide products are in various stages of thedevelopment pipeline, but the lead technologies include gels, lms,tabletsandintravaginal rings(IVRs)(Abdool Karimetal., 2010;Akil etal., 2011;Gargetal., 2010;Malcolmetal., 2010). Thereareanumber of advantagesanddisadvantagesassociatedwiththeleadingDDS. Vaginalgelsarerelevantforpericoitalordailyusebuthavelimitedabilitytodeliverphysicochemicallydiverseagents, arenotamenabletosustainedprotectionandaremessyandmayleakoutofthevaginalcavityafterapplication. Tabletsareeasilyformulatedandmanufacturedbutmayleaveagrainyresiduein thevaginalcavity afterdissolution(Gargetal., 2003).IVRs are currently the only sustained release dosage method andhave enhanced product stability as a solid dosage form, but are rel-ativelycomplicatedandexpensivetofabricate(Malcolmet al.,2010). Vaginal lms are also relevant for pericoital use, have dem-onstrated capability for delivering physicochemically diverseagents, and exhibit enhanced product stability compared tosemi-soliddosageformssuchasgels. However, vaginalmicrobi-cidelmshavereportedloadingsof