Cell-basedin vitromodels for predicting drug permeability

Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides

“…Most microbicide products developed and tested so 61 far in human clinical trials have relied in semi-solid dosage forms, 62 particularly gels. These are coitally-dependent systems (i.e., require 63 administration shortly before/after intercourse) that frequently 64 lead to poor user adherence and, thus, potentially reduced ability 65 to protect against transmission [3]. However, modified and sus- 66 tained drug delivery systems, such as vaginal rings, may be prefer- 67 able and are receiving a lot of the current attention as these can 68 provide coitally-independent options for protection [4].…”

“…572 Cell viability for drug-free NPs was above 70-80% (CC 50 > 300 lM) NPs can dramatically change their cytotoxic profiles [11,12]. observed as compared to their basal levels, except at higher The ability of NPs to modulate the permeability of dapivirine 617 across cell monolayers was investigated as these models provide 618 an efficient way to predict the potential systemic exposure to the 619 drug [63]. HEC-1-A [25] and CaSki [11] cell monolayers, in par-620 ticular, are useful models for studying vaginal drug permeability.…”

The role of mucus in cell-based models used to screen mucosal drug delivery

“…For instance, this allows overcoming the lack of mucus-producing ability of most of the common cell-based membrane models used in drug delivery studies [8]. Also, the composition of artificial mucosal fluids can be clearly defined allowing to reduce bias induced by variable qualitative and quantitative production of mucin-producing cells that are highly dependent on stimuli during handling [128,129].…”

“…The most common approach has been the development of cell-based in vitro models, mostly as cell monolayers [8,9]. Cellular models are usually constructed by seeding epithelial cells on top of semi-permeable membranes made out of polyester or polycarbonate and mounted in specific cell culture plates, like the popular Transwell® systems (Corning, NY).…”

Applications of cell culture studies in pharmaceutical technology

“…Cell-based in vitro models have been used to study drug permeability through buccal (TR146 cell culture), intestinal (Caco-2 cell, TC7, MDCK, LLC-PK1), nasal (cultured nasal cells), pulmonary (Calu-3), ocular (corneal epithelial cells), rectal, vaginal (cervical cell lines) routes 27 . Among these, intestinal permeability is the most studied because the oral route of drug administriation is the most common 28 .…”