Recent advances on anti-HIV vaginal delivery systems development

Antimisiaris, Sophia G.; Mourtas, Spyridon

doi:10.1016/j.addr.2015.03.015

Cited by 40 publications

(41 citation statements)

References 281 publications

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“…Consequently, a reduction in vaginal transmission will have a major impact on the reduction of new HIV-1 infections around the world. Although 24 potential vaginal microbicides are currently under development, there is no efficient method to eliminate vaginal transmission [3]. At the same time, data have shown that the pooled risk estimate for anal intercourse is 1.7%, which is at least 5–6 times higher than the risk estimate for vaginal sex [4].…”

Section: Introductionmentioning

confidence: 99%

Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle

Smith

Daniel

2016

Aids

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Objective Vaginal transmission is crucial to the spread of HIV-1 around the world. It is not yet clear what type(s) of innate defenses against HIV-1 infection are present in the vagina. Here, we aimed to determine whether human vaginal fluid contains exosomes that may possess anti-HIV-1 activity. Methods The exosomal fraction was isolated from samples of vaginal fluids. The presence of exosomes was confirmed by flow cytometry and western blotting. The newly discovered exosomes were tested for their ability to block early steps of HIV-1 infection in vitro using established cell culture systems and real time PCR-based methods. Results Vaginal fluid contains exosomes expressing CD9, CD63 and CD81 exosomal markers. The exosomal fraction of the fluid reduced transmission of HIV-1 vectors by 60%, the efficiency of reverse transcription step by 58.4%, and the efficiency of integration by 47%. Exosomes had no effect on the entry of HIV-1 vectors. Conclusion Human vaginal fluid exosomes are newly discovered female innate defenses that may protect women against HIV-1 infection.

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Section: Introductionmentioning

confidence: 99%

Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle

Smith

Daniel

2016

Aids

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“…A comprehensive summary of clinical trials for topical vaginal microbicides can be found in a recent paper by Antimisiaris et al [73]. To date, there have not been any products approved for use in humans.…”

Section: Introductionmentioning

confidence: 99%

“…Nanotechnology-based drug delivery systems are a promising option to advance the field of microbicides by their ability to (1) facilitate drug/virus interactions, (2) increase synergy for drug cocktails (3) penetrate mucosa tissue, (4) provide sustained and triggered drug release, (5) target HIV susceptible cells, (6) improve drug solubility and permeability, and (7) serve as a drug barrier along the epithelial cell lining [74–76]. Recent review articles published earlier this year discuss the benefits and potential drawbacks of exploring nanotechnology-based solutions to improve the efficacy of vaginal microbicides [73, 77]. …”

Section: Introductionmentioning

confidence: 99%

Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment

Nelson

Zhang

Ganapathi

et al. 2015

Journal of Controlled Release

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The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DDS currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection.

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“…Antimisiaris and Moutas have previously summarized the various gel preparations evaluated in clinical safety and efficacy studies [88]. Gels, also referred to as hydrogels, are semisolid preparations defined as a hydrophilic network of water absorbent polymers dispersed in water.…”

Section: On-demand Vaginal Rectal and Dual Compartment Dosage Formsmentioning

confidence: 99%

On-demand microbicide products: design matters

Patel

Rohan

2017

Drug Deliv. and Transl. Res.

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Sexual intercourse (vaginal and anal) is the predominant mode of HIV (human immune deficiency virus) transmission. Topical microbicides used in an on-demand format (i.e. immediately before or after sex), can be part of an effective tool kit utilized to prevent sexual transmission of HIV. The effectiveness of prevention products is positively correlated with adherence, which is likely to depend on user acceptability of the product. The development of an efficacious and acceptable product is therefore paramount for the success of an on-demand product. Acceptability of on-demand products (e.g. gels, films, and tablets) and their attributes is influenced by a multitude of user-specific factors that span behavioral, life-style, socio-economic, and cultural aspects. In addition, physicochemical properties of the drug, anatomical and physiological aspects of anorectal and vaginal compartments, issues relating to large-scale production and cost can impact product development. These factors together with user preferences determine the design space of an effective, acceptable, and feasible on-demand product. In this review, we summarize the interacting factors that together determine product choice and its target product profile.

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Recent advances on anti-HIV vaginal delivery systems development

Cited by 40 publications

References 281 publications

Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle

Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle

Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment

On-demand microbicide products: design matters

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