Raloxifene (RLX) is a second-generation selective estrogen receptor modulator approved for the prevention of invasive breast cancer in women. Oral therapy of RLX requires daily intake and is associated with side effects that may lead to low adherence. We developed a weekly transdermal delivery system (TDS) for the sustained delivery of RLX to enhance the therapeutic effectiveness, increase adherence, and reduce side effects. We evaluated the weekly transdermal administration of RLX using passive permeation, chemical enhancers, physical enhancement techniques, and matrix- and reservoir-type systems, including polymeric gels. In vitro permeation studies were conducted using vertical Franz diffusion cells across dermatomed human skin or human epidermis. Oleic acid was selected as a chemical enhancer based on yielding the highest drug delivery amongst the various enhancers screened and was incorporated in the formulation of TDSs and polymeric gels. Based on in vitro results, both Eudragit- and colloidal silicon dioxide-based transdermal gels of RLX exceeded the target flux of 24 μg/cm²/day for 7 days. An infinite dose of these gels delivered 326.23 ± 107.58 µg/ cm² and 498.81 ± 14.26 µg/ cm² of RLX in 7 days, respectively, successfully exceeding the required target flux. These in vitro results confirm the potential of reservoir-based polymeric gels as a TDS for the weekly administration of RLX.

This study explored the development of cross-linked gels to potentially provide a physical barrier to vaginal sperm transport for contraception. Two types of gels were formulated, a physically cross-linked iota-carrageenan (C_i) phenylboronic acid functionalized hydroxylpropylmethyacrylate copolymer (PBA)-based (C_i-PBA) gel, designed to block vaginal sperm transport. The second gel was pH-shifting cross-linked C_i-polyvinyl alcohol-boric acid (C_i-PVA-BA) gel, designed to modulate its properties in forming a viscoelastic, weakly cross-linked transient network (due to C_i gelling properties) on vaginal application (at acidic pH of ~3.5–4.5) to a more elastic, densely cross-linked (due to borate-diol cross-linking) gel network at basic pH of 7–8 of seminal fluid, thereby acting as a physical barrier to motile sperm. The gels were characterized for dynamic rheology, physicochemical properties, and impact on sperm functionality (motility, viability, penetration). The rheology data confirmed that the C_i-PBA gel was formed by ionic interactions whereas C_i-PVA-BA gel was chemically cross-linked and became more elastic at basic pH. Based on the screening data, lead gels were selected for in vitro sperm functionality testing. The in vitro results confirmed that the C_i-PBA and C_i-PVA-BA gels created a barrier at the sperm-gel interface, providing sperm blocking properties. For preclinical proof-of-concept, the C_i-PBA gels were applied vaginally and tested for contraceptive efficacy in rabbits, demonstrating only partial efficacy (40–60%). Overall, the in vitro and in vivo results support the development and further optimization of cross-linked gels using commercially available materials as vaginal contraceptives.

Chronic infectious diseases caused by human immunodeficiency virus (HIV) such as Acquired immunodeficiency syndrome (AIDS) remain common throughout the world. An HIV prevention strategy that women can initiate or control in the form of a microbicide was first proposed almost two decades ago. In this study, Tenofovir Disoproxil Fumarate incorporated niosomal gel prepared by reverse phase evaporation technique and characterized. Scanning electron microscopy revealed that the niosomal as well as gel formulation was found to be spherical and non-aggregated. The entrapment efficiency of drug was found to be 40% in the vesicular system. The ratio of gel formulation was kept constant with semen (1:1) shows destruction of the sperm cells. The ability of the vaginal formulation to buffer pH below 6 exhibited good spermicidal activity. In addition, because of compatibility of gel formulation with latex condoms, the gel formulation can be used in combination with the male condom to obtain a maximal protection against pregnancies and sexually transmitted infections. As far as anti-HIV activity of the Tenofovir disoproxil fumarate is considered, it is already been reported as well as Tenofovir Disoproxil Fumarate had been approved by the FDA as a potent anti-HIV drug for HIV. Thus, it is assumed that the formulation will provide control against HIV as well as other sexually transmitted diseases with minimum systemic toxicity.