Enhancing Acyclovir Permeability using SLS Crosslinked β-Cyclodextrin Nanoparticles

Introduction/Objective: Acyclovir, a BCS class III drug (that has high solubility and low permeability) is an antiviral drug used for the treatment of herpes simplex and varicose zoster. To enhance acyclovir's permeability across the intestinal membrane and to improve its bioavailability the β-cyclodextrin (β-CD) nanoparticles of acyclovir were prepared with sodium lauryl sulfate (SLS) as a crosslinking agent. Methods: A phase solubility study was performed with varying ratios of acyclovir to β-CD. Three formulations of acyclovir-loaded β-CD nanoparticles were prepared with drug-β-CD ratios of 1:1, 1:2, and 1:4. The prepared nanoparticle formulations were characterized for FTIR, dynamic light scattering (particle size, polydispersity index, zeta potential) and in vitro permeability studies. Results: Phase solubility study resulted in an "AL type" curve with an association constant (Kc) of 12 M-1 which suggested the formation of a strong complex between acyclovir and β-CD, leading to enhanced solubility of acyclovir with increasing concentrations of β-CD. The FTIR spectrum confirmed the compatibility of acyclovir, β-CD, and SLS in the formulations. Dynamic light scattering analysis demonstrated particle sizes ranging from 152.92 nm to 335.7 nm, with the smallest particles in the 1:4 ratio formulation (152.92 nm), potentially due to higher drug encapsulation. Zeta potential measurements reflected formation of stable nanoparticle suspensions, with the formulation exhibiting a zeta potential of -45.4 mV showcasing optimal stability. In vitro permeation studies revealed that the 1:4 ratio formulation exhibited the highest permeability (84.24 ± 1.94% at the end of 150 min) through the eggshell membrane, implying efficient drug release. This increase in permeability corroborated with its smallest particle size. Conclusion: The study highlights the potential of β-CD nanoparticles (with best performance shown by drug-to-β-CD ratio 1:4) in augmenting acyclovir's delivery, suggesting a promising avenue for improving the drug delivery in viral infections.