The present study aimed to design a PEGylated lipid polymeric nanoparticle system, utilising chitosan, lecithin, and poly (ethylene glycol) (PEG) 2000 that was hypothesised to produce nanoparticles with high encapsulation and good permeability, accompanied by a sustained release profile. PEGylated acyclovir-loaded lecithin-chitosan nanoparticles (PALNs) were formulated and optimised, and the physicochemical properties of PALN were characterised for stability of the nanoparticles. Simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were used to study the in vitro drug release of PALN. In contrast, rabbit intestine was used to evaluate the ex vivo permeation performance for the controlled release of the drugs for 60 days.