Synthesis, Characterization and Safety Evaluation of Sericin-Based Hydrogels for Controlled Delivery of Acyclovir

Moawia M Al-Tabakha,Hamid Ullah,Kaleem Ullah,Shujaat Ali Khan,Nageeb Hassan,Akram Ashames,Ghulam Murtaza

doi:10.3390/ph14030234

Abstract

Conventional formulations of antiviral drug acyclovir have various limitations such as low bioavailability. The current study was aimed at developing polymeric matrices for the controlled delivery of acyclovir using sericin as polymer and acrylic acid (AA) as a monomer. The free radical polymerization technique was used for hydrogel formulation. Briefly, sericin was chemically cross-linked with acrylic acid. N′-N′-methylene bis-acrylamide (MBA) and ammonium persulfate (APS) were used as cross-linker and initiator, respectively. FTIR spectra showed that acyclovir was successfully loaded into sericin hydrogel. SEM micrographs revealed that the outer surface was solid-like and smooth. According to DSC thermograms, the developed polymeric network was thermally stable. Amorphous nature of acyclovir was observed in XRD. The pH of medium and reactants’ concentration affected swelling dynamics and acyclovir release pattern. In addition, drug release occurred through a diffusion-controlled process. Sericin hydrogel suspension was well tolerable up to 3800 mg/kg of rabbits’ body weight. Haematology and serum chemistry results were well within the range signifying normal liver and kidney functions. Similarly, histopathology slides of the rabbit’s vital organs were also in normal condition without causing any histopathological change. It was concluded from the findings that sericin-co-AA polymeric matrices are ideal for the pH-dependent delivery of acyclovir.

Highlights

Acyclovir (Figure 1) is a synthetic purine nucleotide analog having an antiviral effect [1].It acts by binding with HSV-thymidine kinase [2]
This study describes the optimization of formulation parameters and composition to get sericin hydrogels with varied cross-linking densities, good mechanical strength, pH-based swelling dynamics, and controlled drug release behavior
Hydrogels have been synthesized through the method of free radical polymerization

Summary

Introduction

Acyclovir (Figure 1) is a synthetic purine nucleotide analog having an antiviral effect [1]. It acts by binding with HSV-thymidine kinase [2]. Due to poor water-solubility (1.2 mg/mL) [4], short half-life (3 h) [5], poor percutaneous absorption [4], risk of thrombophlebitis after intravenous bolus administration [5], and low oral bioavailability (15–30%) [6], conventional tablets, intravenous formulations, and topical dosage forms of acyclovir are administered to patients in a high-frequency rate (5–6 times a day) [5] and in large doses (200–800 mg) [4] to achieve desired therapeutic response, which is responsible for dose-dependent side effects [5].

Methods

Results

Conclusion