Smart Freeze-Dried Bigels for the Prevention of the Sexual Transmission of HIV by Accelerating the Vaginal Release of Tenofovir during Intercourse

Abstract

Sub-Saharan African women are still at risk from the human immunodeficiency virus (HIV), and sex with men is the main route of transmission. Vaginal formulations containing antiretroviral drugs are promising tools to give women the power to protect themselves. The aim of this work was to obtain freeze-dried bigels containing pectin, chitosan, or hypromellose for the vaginal controlled release of Tenofovir, which is accelerated in the presence of semen. Nine batches of bigels were formulated using different proportions of these polymers in the hydrogel (1, 2, and 3% w/w). The bigels obtained were freeze-dried and then underwent hardness and deformability, mucoadhesion, swelling, and drug release tests, the last two in simulated vaginal fluid (SVF) and SVF/simulated seminal fluid (SSF) mixture. The formulation containing 3% pectin (fd3P) has the highest values for hardness, resistance to deformation, and good mucoadhesivity. Its swelling is conditioned by the pH of the medium, which is responsive to the controlled release of Tenofovir in SVF, with the fastest release in the SVF/SSF mixture. fd3P would be an interesting smart microbicidal system to allow faster release of Tenofovir in the presence of semen, and thus increase women’s ability to protect themselves from the sexual transmission of HIV.

Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates

“…TAF exhibited an improved antiviral activity and safety profile related to renal and bone toxicity [30][31][32]. Therefore, TFV, TDF and in particular TAF represent key compounds for the treatment of chronic hepatitis B and HIV infections and are thus a subject of intense research in the area of new drug delivery systems [33][34][35][36][37][38][39][40].…”

Mucoadhesive Vaginal Discs based on Cyclodextrin and Surfactants for the Controlled Release of Antiretroviral Drugs to Prevent the Sexual Transmission of HIV

“…A study was carried out using a Texture Analyser (TA.XTplus, Stable Micro Systems, Surrey, UK) to determine the penetration work (a measure of gel consistency) and the detachment work (related to gel adhesiveness). The characterisation was done using the protocol of Martín-Illana et al, with a 2 cm diameter probe and a 5 kg load cell [17]. Specifically, 80 mL of the evaluated gel was placed in a 100 mL beaker.…”

“…Pose size distribution (PSD) was Unloaded vaginal discs were also prepared by adding the required amount of gel to obtain discs with the same composition as their equivalent drug-loaded disc (except for the active principle, obviously). A Lio-Labor®freeze-dryer (Telstar, Barcelona, Spain) was used to obtain the discs, using a freezing temperature of -45 • C, a sublimation pressure of 4.5 × 10 −4 atm and a sublimation temperature between -45 • C and 25 • C [17,26]. The composition of all the prepared batches is shown in Table 1.…”

“…The probe descended at a speed of 1 mm/s and pressed the mucosa with a force of 500 g for 30 s (the same conditions established in the mucoadhesion time test). After this time, the probe was raised at a speed of 0.1 mm/s, and the force required to detach the disc from the mucosa was recorded [17]. This test was performed in triplicate for each batch.…”

“…However, the main problems cited by users are leakage and messiness after administration [15]. Freeze-drying is one strategy to solve this problem with semi-solid formulations, involving a process in which water is removed from the pharmaceutical form [16,17]. These freeze-dried gels are equally convenient to administer and allow the rapid release of the active substance, since they can quickly rehydrate in the presence of vaginal fluid [18].…”