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  • Title: Alginate microbead-encapsulated silver complexes for selective delivery of broad-spectrum silver-based microbicides.
    Author: Damelin LH, Fernandes MA, Tiemessen CT.
    Journal: Int J Antimicrob Agents; 2015 Oct; 46(4):394-400. PubMed ID: 26184337.
    Abstract:
    In sub-Saharan Africa, human immunodeficiency virus (HIV) infections are predominantly acquired via heterosexual contact, and women are at greatest risk of being infected. This region also has the highest rates of sexually transmitted infections (STIs) per capita worldwide; STIs are strongly associated with increased HIV transmission. Therefore, there is an urgent requirement for microbicides that are active against HIV and STIs. Silver compounds exhibit broad antimicrobial activity, making them potentially ideal broad-spectrum microbicides. However, for silver compounds to be effective microbicides, they must be active within seminal fluid and the delivery vehicle used must protect the silver microbicide from vaginal fluid components but selectively release it during intercourse and/or following ejaculation. In this study, silver complexes were synthesised from the ligands saccharin, benzimidazole and 8-hydroxyquinoline and their microbicidal activity was assessed. We show that a silver saccharinate-benzimidazole complex (AgSB) exhibited activity against HIV-1, herpes simplex virus type 2 (HSV-2) and Neisseria gonorrhoeae at concentrations significantly below LD(50) levels for the vaginal mucosal cell line SiHa. Furthermore, we show that alginate microbeads are stable in vaginal fluid simulant but rapidly dissolve in seminal fluid simulant. Finally, we have established that microbead-encapsulated AgSB, dissolved in seminal fluid simulant, is active against the above pathogens, albeit at higher concentrations for HIV-1. This research therefore highlights, for the first time, the potential use of silver complexes encapsulated in alginate microbeads as a novel system for the delivery and selective release of broad-spectrum silver-based microbicides within the vaginal milieu during sexual intercourse/after ejaculation.
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