Nanotech-derived topical microbicides for HIV prevention: The road to clinical development

Sánchez-Rodríguez, Javier; Vacas-Córdoba, Enrique; Gómez, Rafael; Mata, F. Javier de la; Muñoz‐Fernández, María Ángeles

doi:10.1016/j.antiviral.2014.10.014

Cited by 24 publications

(13 citation statements)

References 152 publications

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“…17,19,20 Some time ago, the main limitations of the first topical "nanomicrobicide" PLL-dendrimer SPL7013 were the lack of broad anti-HIV-1 activity against R5-HIV-1 strains 21 and the increased risk for HIV-1 acquisition associated with epithelial injury after 7-14 days of twice-daily administration. 22 Seminal amyloid is critical for decreasing the antiviral efficacy of SPL7013 PLL-dendrimer and anionic polymers because semen lacking HIV-enhancing activity does not impair the drug efficacy, whereas synthetic semen-derived enhancer of viral infection amyloid fibrils decrease the drug efficacy as the semen itself.…”

Section: Discussionmentioning

confidence: 99%

“…17,19,20 G2-S16 presents high biosafety and low toxicity in PBMC, shows high anti-HIV activity in urogenital epithelial cells against HIV-1-R5-, X4-, and dual-tropic viruses, their various subtypes, and T/F HIV-1 strains. G2-S16 is stable over a broad pH range (pH in vagina: 4-5.8 and pH in seminal fluid: 8-8.5), maintaining the anti-HIV-1 activity.…”

Section: Discussionmentioning

confidence: 99%

“…G2-S16 prevents HIV entry in a manner that is independent of the number of viral particles or the presence of semen, and G2-S16 also acts as an inhibitor of cell-to-cell transmission. 19,20 To summarize, G2-S16 possesses a multifactorial and nonspecific ability because it acts as a virucidal agent, an inhibitor of entry of the virus, a barrier to infection for long periods of time, and an inhibitor of cell-to-cell HIV-1 transmission.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

Ceña-Díez¹,

García-Broncano²,

Fj³

et al. 2016

IJN

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The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV)-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine)-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

Ceña-Díez¹,

García-Broncano²,

Fj³

et al. 2016

IJN

Self Cite

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“…In this section, the application of nanomedicine pertaining to on-demand dosage forms is discussed. Interested readers can access reviews published in this area [121, 122]. Nanomedicine or nanoparticles are structures with size less than 1000 nm in each direction.…”

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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“…A variety of nano-architectures (i.e. liposomes, dendrimers, polymeric NP, nanocrystals, nanofibers and inorganic NP) are being explored as formulations for novel microbicide candidates 3-5 . Taking into account the NP composition, all NP-based systems designed so far for anti-HIV microbicidal applications can be divided into two major groups: 1) NP formed by components that have intrinsic antiretroviral activity 6, 7 ; 2) NP containing a cargo with antiretroviral activity, which is combined and stabilized with certain carrier molecules such as poly(lactic-co-glycolic acid) (PLGA) and PLGA blends 8-11 , as well as other polymeric carriers 12-14 .…”

Section: Introductionmentioning

confidence: 99%

Hydrophobic-core PEGylated graft copolymer-stabilized nanoparticles composed of insoluble non-nucleoside reverse transcriptase inhibitors exhibit strong anti-HIV activity

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Valuev-Elliston

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Benzophenone-uracil (BPU) scaffold-derived candidate compounds are efficient non-nucleoside reverse transcriptase inhibitors (NNRTI) with extremely low solubility in water. We proposed to use hydrophobic core (methoxypolyethylene glycol-polylysine) graft copolymer (HC-PGC) technology for stabilizing nanoparticle-based formulations of BPU NNRTI in water. Co-lyophilization of NNRTI/HC-PGC mixtures resulted in dry powders that could be easily reconstituted with the formation of 150-250 nm stable nanoparticles (NP). The NP and HC-PGC were non-toxic in experiments with TZM-bl reporter cells. Nanoparticles containing selected efficient candidate Z107 NNRTI preserved the ability to inhibit HIV-1 reverse transcriptase polymerase activites with no appreciable change of EC50. The formulation with HC-PGC bearing residues of oleic acid resulted in nanoparticles that were nearly identical in anti-HIV-1 potency when compared to Z107 solutions in DMSO (EC50=7.5±3.8 vs. 8.2±5.1 nM). Therefore, hydrophobic core macromolecular stabilizers form nanoparticles with insoluble NNRTI while preserving the antiviral activity of the drug cargo.

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Nanotech-derived topical microbicides for HIV prevention: The road to clinical development

Cited by 24 publications

References 152 publications

Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

On-demand microbicide products: design matters

Hydrophobic-core PEGylated graft copolymer-stabilized nanoparticles composed of insoluble non-nucleoside reverse transcriptase inhibitors exhibit strong anti-HIV activity

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