Bilosomes nanocarriers for improved oral bioavailability of acyclovir: A complete characterization through in vitro, ex-vivo and in vivo assessment

Acyclovir (ACV) is an antiviral drug given as tablet that has variable and incomplete absorption from the gastrointestinal tract. Also the absorption is saturated with multi-dose regime leading to only 10-20% bioavailability. Since the drug absorption site is the upper segment of the small intestine so we hypothesised that absorption of acyclovir would increase through novel carriers such as bilosomes which are resistant to digestive enzymes disruption and offer greater drug absorption owing to higher tissue penetration. Also, reduction in drug dose would be possible through bilosomes oral delivery. To prove our hypothesis, ACV loaded bilosomes were prepared by thin film hydration technique and optimized by Box-Behnken statistical design. The mean vesicle size, polydispersity index and entrapment efficiency (%) of optimized bilosome formulation was observed to be 121.2 +/- 3.21 nm, 0.261 +/- 0.023 and 83.32 +/- 5.46% respectively. In vitro release of ACV bilosomes at pH 6.8 was significantly higher (95.1 +/- 7.27%) compared to ACV suspension and marketed formulation 40.23 +/- 5.32% and 52.74 +/- 5.84 respectively. Ex vivo gut permeation study revealed a good enhancement in penetration of bilosomes compared to ACV solution and marketed formulation which was further confirmed by confocal laser scanning microscopy which showed high penetration of bilosomes owing to vesicle stability against intestinal bile salts. Pharmacokinetic study in Wistar rats showed 4.36 and 2.5 fold increase in relative bioavailability with bilosomes (p<0.05) at a dose of 5mg/Kg body weight compared to ACV suspension and its marketed formulation respectively. Bilosomes treated tissue sections of the kidney, liver and intestine showed normal histology at the tested dose for a period of 24 h. Therefore, it is concluded that bilosomes are the safe carriers for improved absorption and bioavailability of acyclovir.