Women are particularly vulnerable to sexual HIV-1 transmission. Oral pre-exposure prophylaxis (PrEP) with
tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) is highly effective in avoiding new infections in men,
but protection has only been shown to be moderate in women. Such differences have been associated, at least
partially, to poor drug penetration of the lower female genital tract and the need for strict adherence to
continuous daily oral intake of TDF/FTC. On-demand topical microbicide products could help circumvent these
limitations. We developed electrospun fibers based on polycaprolactone (PCL fibers) or liposomes associated to poly(vinyl alcohol) (liposomes-in-PVA fibers) for the vaginal co-delivery of TDF and FTC, and assessed their
pharmacokinetics in mice. PCL fibers and liposomes-in-PVA fibers were tested for morphological and physico chemical properties using scanning electron microscopy, differential scanning calorimetry and X-ray diffrac tometry. Fibers featured organoleptic and mechanical properties compatible with their suitable handling and vaginal administration. Fluorescent quenching of mucin in vitro – used as a proxy for mucoadhesion – was intense
for PCL fibers, but mild for liposomes-in-PVA fibers. Both fibers were shown safe in vitro and able to rapidly
release drug content (15–30 min) under sink conditions. Liposomes-in-PVA fibers allowed increasing genital drug concentrations after a single intravaginal administration when compared to continuous daily treatment for five days with 25-times higher oral doses. For instance, the levels of tenofovir and FTC in vaginal lavage were around 4- and 29-fold higher, respectively. PCL fibers were also superior to oral treatment, although to a minor extent (approximately 2-fold higher drug concentrations in lavage). Vaginal tissue drug levels were generally low for all treatments, while systemic drug exposure was negligible in the case of fibers. These data suggest that proposed fibers may provide an interesting alternative or an ancillary option to oral PrEP in women.This work was financed by Programa Gilead GÉNESE (refs. PGG/
046/2015) and Portuguese funds through FCT - Fundação para a Ciência
e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in
the framework of the project “Institute for Research and Innovation in
Health Sciences” UID/BIM/04293/2019. The work was also financed by
FCT in the framework of the Strategic Funding UID/FIS/04650/2019
and in the ambit of the project POCI-01-0145-FEDER-032651 and
PTDC/NAN-MAT/326512017, co-financed by the FEDER, through
COMPETE 2020, under PORTUGAL 2020, and FCT. Marlene Lúcio
thanks FCT and ERDF for doctoral position Ref. CTTI-150/18-CF(1) in
the ambit of the project CONCERT (POCI-01-0145-FEDER-032651 and
PTDC/NAN-MAT/326512017)