Abstract
Treatment of herpes simplex infection requires high and frequent doses of oral acyclovir to attain its maximum therapeutic effect. The current therapeutic regimen of acyclovir is known to cause unwarranted dose-related adverse effects, including acute kidney injury. For this reason, a suitable delivery system for acyclovir was developed to improve the pharmacokinetic limitations and ultimately administer the drug at a lower dose and/or less frequently. In this study, solid lipid nanoparticles were designed to improve the oral bioavailability of acyclovir. The central composite design was applied to investigate the influence of the materials on the physicochemical properties of the solid lipid nanoparticles, and the optimized formulation was further characterized. Solid lipid nanoparticles formulated from Compritol 888 ATO resulted in a particle size of 108.67 ± 1.03 nm with an entrapment efficiency of 91.05 ± 0.75%. The analyses showed that the optimum combination of surfactant and solid lipid produced solid lipid nanoparticles of good quality with controlled release property and was stable at refrigerated and room temperature for at least 3 months. A five-fold increase in oral bioavailability of acyclovir-loaded solid lipid nanoparticles was observed in rats compared to commercial acyclovir suspension. This study has presented promising results that solid lipid nanoparticles could potentially be used as an oral drug delivery vehicle for acyclovir due to their excellent properties.
Highlights
Acyclovir (C8H11N5O3) is an antiviral drug derived from a guanosine analog
The variation in size, zeta potential and polydispersity index (PdI) of solid lipid nanoparticles (SLN) were predicted using response surface methodology as these responses depend on the composition of nanoparticles
In order to assess the stability of the drug-free and acyclovir-loaded SLN dispersions, all SLN samples were stored in an amber-colored bottle for 90 days at three different temperatures; 4 ± 2 ◦C, 25 ± 2 ◦C with 60 ± 5% relative humidity and 40 ± 2 ◦C with 75 ± 5% relative humidity following the method described in previous studies with slight modification [54,55]
Summary
Acyclovir (C8H11N5O3) is an antiviral drug derived from a guanosine analog. It is the gold standard drug prescribed by physicians as first-line therapy and prophylactic treatment for herpes simplex virus (HSV) infections. Studies found that cyclosporine A loaded in SLN dispersion exhibited sustained-release property and improved in its solubility [22,23] These results highlight the potential of SLN for oral drug delivery over other carrier systems. The conventional approach, which is most commonly practiced, is to change a single factor or variable while keeping the other independent factors constant to observe the effect of composition or process variables on quality attributes This approach requires a large number of experiments, and the interaction between factors is difficult to study. It is an innovative idea that, in this study, CCD was employed to optimize the SLN formulation for encapsulation of acyclovir by investigating the effect of two independent variables, the composition of Compritol 888 ATO (solid lipid) and Tween 80 (surfactant), on three dependent variables, namely particle size, polydispersity index (PdI) and zeta potential. The optimized formulation of acyclovir-loaded SLN was evaluated for its pharmacokinetic profile to support the study hypothesis; acyclovir-loaded SLN increases the oral bioavailability and absorption of acyclovir when administered orally in an in vivo model
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