In Vitro Assessment of Acyclovir Permeation Across Cell Monolayers in the Presence of Absorption Enhancers

Abstract

The aim of the investigation was to establish transepithelial permeation of acyclovir across Caco-2 and Madin-Darby canine kidney (MDCK) cell monolayers and attempt to improve its permeation by employing absorption enhancers (dimethyl β cyclodextrin, chitosan hydrochloride and sodium lauryl sulfate) and combinations thereof. Caco-2 and MDCK cell monolayers have been widely employed in studying drug transport, mechanisms of drug transport, and screening of absorption enhancers and excipients. Transepithelial electrical resistance and permeation of ^99mTc-mannitol were employed as control parameters to assess the tight junction and paracellular integrity. Permeation of acyclovir in the presence of absorption enhancers was found to be significantly higher compared with drug permeation in their absence when assessed as apparent permeability coefficients (P_app). Synergistic improvements in P_app values of acyclovir were obtained in case-selected combinations of absorption enhancers; dimethyl β cyclodextrin–chitosan hydrochloride, chitosan hydrochloride–sodium lauryl sulfate, and dimethyl β cyclodextrin–sodium lauryl sulfate, were used. Recovery and viability assessment studies of both cell monolayers suggested reestablishment of paracellular integrity and no damage to cell membranes. Significantly improved permeation of acyclovir in the presence of selected combinations of absorption enhancers may be used as a viable approach in overcoming the problem of limited oral bioavailability of acyclovir.

Keywords:

• acyclovir
• absorption enhancers
• permeation
• Caco-2
• MDCK
• TEER
• ^99mTc-mannitol