The effect of amphiphilic N,N,N-trimethyl-O-octadecyl chitosan on the oral bioavailability of acyclovir

Acyclovir (ACV), an analog of 2′-deoxyguanosine, exhibits poor bioavailability due to limited permeability. In this study, the aim was to improve the bioavailability and permeability of ACV. N,N,N-trimethyl-O-octadecyl chitosan (TMSC) was synthesized by covalently bonding a long alkyl chain and a quaternary ammonium group onto chitosan. The chemical structure of TMSC was characterized by Fourier transform infrared (FT-IR) spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetry (TG), and differential thermogravimetry (DTG). The biological safety of TMSC was evaluated using a hemolysis experiment, which resulted in a hemolysis rate of 6.63% at the highest concentration (3 mg/mL). TMSC was used to prepare acyclovir nanoparticle (ACV NP) based on the Box–Behnken design, and characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS) to determine size and morphology. Furthermore, the permeability of ACV NP was investigated using a non-everted intestinal sac model. ACV NP exerted a 1.9-fold higher effect on the ileum than ACV. In vivo, the relative bioavailability of ACV NP was ∼4.5-fold greater than that of the ACV suspension. These results suggest that ACV NP augment permeability and effectiveness of ACV.