Formulation and evaluation of poly(jasmine lactone) based micelles for improving the oral permeability of acyclovir

Abstract

Acyclovir (ACV), an antiviral drug, belongs to the BCS class III drug with intermediate solubility and low permeability. The limited permeability leads to low drug absorption, making it poorly bioavailable. Consequently, to achieve the ACV concentration within the therapeutic range, frequent dosing is required which can lead to several side effects. Thus, increasing the permeability of ACV is critical for enhancing bioavailability, overall therapeutic outcomes and patient compliance. Advanced drug delivery systems (DDS), such as polymeric micelles, can be employed to enhance ACV bioavailability, as they offer distinct advantages. Notably, anionic polymeric micelles based on acid functionalized poly(jasmine lactone) copolymer were employed for the first time to improve ACV solubility and permeability. Micelles with size of approx. 100 nm were able to improve the aqueous solubility of ACV from 1.81 mg to 4.32 mg/mL. The anti-viral assay results reveal that ACV loaded micelles are equally effective in both prophylactic and therapeutic settings towards inhibiting herpes simplex virus type 1 compared to free ACV. The permeability study performed via phospholipid vesicle-based permeation assay (PVPA) indicated an improvement in ACV permeability when loaded in polymeric micelles compared to free ACV. This increase was observed both in absence as well as in the presence of an additional mucus layer. In silico simulations performed on GastroPlus® (GPX) software supported the outcomes of PVPA assay in a simulated human model. The obtained results indicated that negatively charged poly(jasmine lactone) micelles could significantly improve the therapeutic outcome of ACV by improving its solubility and oral permeability.