Development and optimisation of mucoadhesive nanoparticles of acyclovir using design of experiments approach

Abstract

The aim of our study was to improve the bioavailability of acyclovir (ACV) by delivery of mucoadhesive nanoparticles (NPs) and controlled delivery of drug at its absorption window. Central composite design was used by which the effects of independent variables (gelatin and Pluronic F-68) on various responses such as particle size, polydispersity index, entrapment efficiency, loading efficiency, drug release and mucoadhesive strength were studied. The optimised formulation was evaluated for morphology, stability, pharmacokinetic and gastrointestinal tracking. The optimised NPs were found to be nearly spherical. Changes in characteristics of NPs were not significant after six months of accelerated stability studies. In vivo mucoadhesion study showed significant retention of mucoadhesive NPs in upper gastro-intestinal tract for more than 12 h. Pharmacokinetic study in rats revealed that mucoadhesive NPs could maintain relatively steady plasma concentration of ACV for more than 10 h. The AUC0-∞ and mean residence time of optimised formulation (7527.9 ng h/mL and 12.09 h) were significantly high than tablet dispersion (3841.13 ng h/mL and 7.97 h).

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“…The design comprised of simulated center points and other points lying at the midpoints of each edge of the multidimensional cube which will describe the section of attention for assessing the main effects, interactions effects and quadratic effects of the formulation factors 31 . The dependent response variable (Y) of the non-linear quadratic model was clarified via the resulting equation 32 .…”

Enhancement of oral bioavailability of natural compounds and probiotics by mucoadhesive tailored biopolymer-based nanoparticles: A review

“…NPs having a mean particle size of ≈445 nm and 76% encapsulation efficiency showed high and gradual swelling capacity in acid gastric fluid, as well as excellent capacity to adhere to the stomach mucosa of male Sprague Dawley rats. Similarly, mucoadhesive gelatin NPs loaded with an antiviral guanosin-derived compound (acyclovir) also showed prolonged retention in the upper GI tract, helping to maintain high drug plasmatic levels in rats (Kharia & Singhai, 2015). The crosslinking between gelatin and oxidized gum arabic has been applied in the preparation of composite nanogels for encapsulation and controlled release of curcumin.…”

Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles

“…Stable nano systems can be obtained when the weight ratio of the drug to stabilizer is 20:1 to 2:1. For increasing the intestinal adhesion surface modification of nanoparticles may be required by using mucoadhesive polymers, as cationic polymers adhere to negative surface of mucin of gastric mucosa 93 . Surface modification of paclitaxel nanocrystals using synthesized pluronic grafted chitosan copolymer has shown to improve relative bioavailability by modulating intestinal P-gp efflux system 94 .…”