Fabrication and characterization of polymeric nanoparticle for efficient and sustained delivery of Acyclovir for antiviral therapy and in-silico study using Pk-Sim software

Purpose The aim of this study is to develop the nanoparticles of the weakly water-soluble antiviral medication Acyclovir using biodegradable and biocompatible natural polymer to overcome it’ s poor oral bioavailability and frequent dosing frequency were the goals of this work. Methods The ionic gelation method was used to prepare acyclovir loaded chitosan nanoparticle using STPP (Sodium tripolyphosphate) as the crosslinking agent. The formulations were characterized by determining particle size, surface morphology, percentage of yield, entrapment efficiency, drug- excipient compatibility (FT-IR), in-vitro release study and in-silico study. Results The FT-IR shows no incompatibility between the drug and the excipients. The analysis of dynamic light scattering indicated that nanoparticles were with it’s nanometric range (within 100 nm), demonstrating moderate polydispersity and SEM shows spherical morphology with smooth surface. The entrapment efficiency showed ⁓98% which indicates that chitosan is a potential carrier for the acyclovir. In-vitro release study illustrates sustain drug release over the time period and drug release kinetic best fitted in korsemeyer-peppas model which indicates diffusion-controlled release of the drug. Additionally, in-silico PBPK model predicted improved plasma profile compared to the conventional oral dosage form. Conclusion The findings suggested that the optimized formulation, especially F3, holding promise for sustained and controlled delivery of Acyclovir, potentially reducing dosing frequency and minimizing side effects.