Formulation and delivery of anti-HIV rectal microbicides: Advances and challenges

On-demand microbicide products: design matters

“…HIV transmission via the rectal route is not well understood, however, it likely follows a similar pattern as the vaginal route. Upon viral deposition through semen in the rectal cavity, cell free or cell-associated virus can be involved in transmission [14]. HIV virions can access immune cells by migrating across the epithelial membrane through intercellular junctions and other pathways.…”

“…Previous reviews have described in detail the anatomical and physiological aspects of the rectum and vagina that influence drug delivery [19, 14]. The attributes of a microbicide product such as physical state, geometry, application volume, formulation composition (excipients), dilution, spreadability, and mucoadhesion must be tailored toward the anatomical and physiological context of use for greater acceptability and efficacy.…”

“…The anatomical aspects of rectum relevant to microbicide delivery has been recently reviewed [14]. The rectum is physiologically much different from the vagina.…”

“…Thus, the rectal environment is easily disrupted when products with extreme pH are introduced. One significant difference between the anorectal and vaginal compartments is that the target immune cells are present in much higher quantities in the rectum as compared to in the vagina [14]. Moreover, the T cells localized in the rectum are activated and express increased CCR5, a coreceptor used by HIV-1 for cell attachment.…”

“…Unsatisfactory results from these studies unequivocally showed that rectal microbicide delivery needs products with varied attributes suitable to the anatomical and physiological environment of the rectal compartment. Previous reviews have summarized preclinical and clinical rectal microbicide studies utilizing vaginal products [41, 14]. Most notably, RMP-02/MTN-006 [42] conducted a rectal safety study using a previously developed vaginal TFV gel.…”