Abstract
Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral bioavailability is low; therefore, frequent and high doses are prescribed for optimum therapeutic efficacy. Moreover, the current therapeutic regimen of acyclovir is associated with unwarranted adverse effects, hence prompting the need for a suitable drug carrier to overcome these limitations. This study aimed to develop solid lipid nanoparticles (SLNs) as acyclovir carriers and evaluate their in vivo pharmacokinetic parameters to prove the study hypothesis. During the SLN development process, response surface methodology was exploited to optimize the composition of solid lipid and surfactant. Optimum combination of Biogapress Vegetal 297 ATO and Tween 80 was found essential to produce SLNs of 134 nm. The oral bioavailability study showed that acyclovir-loaded SLNs possessed superior oral bioavailability when compared with the commercial acyclovir suspension. The plasma concentration of acyclovir-loaded SLNs was four-fold higher than the commercial suspension. Thus, this investigation presented promising results that the method developed for encapsulation of acyclovir offers potential as an alternative pathway to enhance the drug’s bioavailability. In conclusion, this study exhibited the feasibility of SLNs as an oral delivery vehicle for acyclovir and therefore represents a new promising therapeutic concept of acyclovir treatment via a nanoparticulate drug delivery system.
Highlights
Herpes simplex virus (HSV) infection constitutes a significant health and financial burden globally [1,2]
The experimental data acquired for all response variables based on Central Composite Design (CCD) matrix were used to determine the model of best fit for the independent variables of solid lipid nanoparticles (SLNs)
Based on the analysis and data obtained from the present study, the preparation, optimization, characterization and potential application of SLNs as a nanoparticulate acyclovir carrier were well explored
Summary
Herpes simplex virus (HSV) infection constitutes a significant health and financial burden globally [1,2]. The World Health Organization (WHO) reported that the prevalence of HSV Type 2 infection was about 491 million aged up to 49 years globally in 2016, while oral HSV Type 1 has infected about 3583.5 million people, which is more common than the genital HSV Type 1 infection, estimated around 122–192 million cases [2]. Acyclovir known as acycloguanosine is a guanosine analog with an attachment of aliphatic group on the side chain (9-[2-hydroxyethoxymethyl] guanine). This drug is efficient against most species of the herpes virus family and actively absorbed in the upper gastrointestinal tract (GIT), the duodenum as well as the jejunum. The terminal half-life of acyclovir is short, about 2.5–3 h following drug administration [7,8]
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