Targeted microbicides for preventing sexual HIV transmission

Coutinho, Catarina; Sarmento, Bruno; Neves, José das

doi:10.1016/j.jconrel.2017.09.030

Cited by 18 publications

(10 citation statements)

References 104 publications

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“…The development of nanotechnology-based systems, in particular, is thought to hold the potential to improve the prophylactic performance of ARV drugs by providing their sustained release and sustaining protective concentrations at the mucosa [11]. Furthermore, the possibility of modulating specific drug targeting through, for example, functionalization of the nanosystem surface, is also possible [12].…”

Section: Introductionmentioning

confidence: 99%

Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention

et al. 2019

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HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evaluate the physicochemical characteristics of both drugs, and to study their biophysical impact in lipid model systems. Results from these pre-formulation studies defined hydrogels as adequate vehicles to incorporate TDF-loaded liposomes and FTC. After studying interactions with mucin, zwitterionic liposomes with a mean diameter of 134 ± 13 nm, an encapsulation TDF efficiency of approximately 84%, and a transition temperature of 41 °C were selected. The chosen liposomal formulation was non-cytotoxic to HEC-1-A and CaSki cells, and was able to favor TDF permeation across polysulfone membranes (Jss = 9.9 μg·cm−2·h−1). After the incorporation of TDF-loaded liposomes and FTC in carbomer hydrogels, the drug release profile was sustained over time, reaching around 60% for both drugs within 3–6 h, and best fitting the Weibull model. Moreover, liposomal hydrogels featured pseudoplastic profiles that were deemed suitable for topical application. Overall, the proposed liposomal hydrogels may constitute a promising formulation for the vaginal co-delivery of TDF/FTC.

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Section: Introductionmentioning

confidence: 99%

Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention

et al. 2019

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“…Vaginal microbicides offer a promising strategy in preventing sexual transmission of human immunodeficiency virus type 1 (HIV-1) and other genital tract infections [1, 2]. The microbicides should not interfere in the ability of genital mucosa to provide protection against other pathogens.…”

Section: Introductionmentioning

confidence: 99%

G2-S16 dendrimer microbicide does not interfere with the vaginal immune system

et al. 2019

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It is essential that prophylactic drugs do not interfere with the normal function of the immune system. The use of nanoparticles as vaginal microbicides is a promising prevention strategy against sexually transmitted infections. With that aim, our group is working with the G2-S16, a second generation carbosilane dendrimer with sulfonate groups in the periphery, which has been previously shown to be effective against HIV-1 and HSV-2 infection, and it is now on the road to clinical trials. Our objective in this new study is to assess the effects of G2-S16 on the immune barrier of the female reproductive tract. The expression of differentiation, maturation and activation markers was measured in epithelial cells, dendritic cells, M and GM macrophages, and T cells using RT-qPCR and flow cytometry. The results demonstrate that G2-S16 does not alter the natural immunity of the vagina, strongly supporting the biosafety of this dendrimer for clinical use.

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“…Based on the mechanism of virus invasion, vaginal microbicides were developed to have adequate epithelial permeability and acceptable pharmacokinetic and safety profiles, as well as targeting the critical steps of HIV transmission [ 14 , 107 ]. In addition, changes in vaginal pH and the dilution of microbicides are also considerations not to be overlooked, since seminal fluid can collectively lead to dilution, three units of change in pH, and increase drug interaction with fructose moieties present in semen [ 108 ].…”

Section: Vaginal Drug Delivery Systems: History and Present Therapeuticsmentioning

confidence: 99%

Application of Sol–Gels for Treatment of Gynaecological Conditions—Physiological Perspectives and Emerging Concepts in Intravaginal Drug Delivery

Thapa

Gurung

Parat

et al. 2022

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Approaches for effective and sustained drug delivery to the female reproductive tract (FRT) for treating a range of gynaecological conditions remain limited. The development of versatile delivery platforms, such as soluble gels (sol–gels) coupled with applicators/devices, holds considerable therapeutic potential for gynaecological conditions. Sol–gel systems, which undergo solution-to-gel transition, triggered by physiological conditions such as changes in temperature, pH, or ion composition, offer advantages of both solution- and gel-based drug formulations. Furthermore, they have potential to be used as a suitable drug delivery vehicle for other novel drug formulations, including micro- and nano-particulate systems, enabling the delivery of drug molecules of diverse physicochemical character. We provide an anatomical and physiological perspective of the significant challenges and opportunities in attaining optimal drug delivery to the upper and lower FRT. Discussion then focuses on attributes of sol–gels that can vastly improve the treatment of gynaecological conditions. The review concludes by showcasing recent advances in vaginal formulation design, and proposes novel formulation strategies enabling the infusion of a wide range of therapeutics into sol–gels, paving the way for patient-friendly treatment regimens for acute and chronic FRT-related conditions such as bacterial/viral infection control (e.g., STDs), contraception, hormone replacement therapy (HRT), infertility, and cancer.

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Targeted microbicides for preventing sexual HIV transmission

Cited by 18 publications

References 104 publications

Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention

Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention

G2-S16 dendrimer microbicide does not interfere with the vaginal immune system

Application of Sol–Gels for Treatment of Gynaecological Conditions—Physiological Perspectives and Emerging Concepts in Intravaginal Drug Delivery

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