title: 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 beta 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 (Papp). Synergistic improvements in Papp values of acyclovir were obtained in case-selected combinations of absorption enhancers; dimethyl beta cyclodextrin-chitosan hydrochloride, chitosan hydrochloride-sodium lauryl sulfate, and dimethyl beta 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.
authors: Department of Pharmacy, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, India.
authors: Pranav
authors: P
authors: Shah
authors: Viral
authors: V
authors: Jogani
authors: Pushpa
authors: P
authors: Mishra
authors: Anil Kumar
authors: AK
authors: Mishra
authors: Tamishraha
authors: T
authors: Bagchi
authors: Ambikanandan
authors: A
authors: Misra
mesh_terms: D000212:Acyclovir / Q000493:pharmacokinetics*; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D001692:Biological Transport; D018938:Caco-2 Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004285:Dogs; D004357:Drug Synergism; D017097:Electric Impedance; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008353:Mannitol / Q000378:metabolism; D010539:Permeability; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D005079:Excipients; D047392:beta-Cyclodextrins; D012967:Sodium Dodecyl Sulfate; D008353:Mannitol; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D048271:Chitosan; D000212:Acyclovir