Abstract
Aims: This study aimed to develop and evaluate mucoadhesive microspheres for the controlled release of zidovudine using a novel dual-functionalized polymer.
Background: Mucoadhesive polymers have recently been widely used to prolong the GI residence time and to modulate the release impact of various mucoadhesive dosage forms. In the present study, a recently synthesized chitosan derivative, chitosan-2-mercapto benzoic acid, was used as a mucoadhesive polymer, which was further developed as a dosage form for improving oral bioavailability of zidovudine drug.
Objective: The objective of this study is to evaluate the impact of a novel thiolated derivative, chitosan-2-mercaptobenzoic acid, on the oral bioavailability of the drug zidovudine.
Methods: The microspheres were prepared using an emulsification crosslinking method with TPP as the crosslinking agent. Techniques such as FTIR, and DSC were employed to analyze the microspheres, along with drug content, entrapment efficiency, dissolution studies, mucoadhesion, ex vivo permeation, and in vivo evaluations.
Results: Results from FTIR spectroscopy and DSC analysis revealed no interaction between the drug and polymers. The release kinetics and characterization assessments indicated a zero-order release profile with anomalous and super case-II transport types. Ex vivo permeation studies on goat intestinal mucosa demonstrated enhanced mucoadhesive properties and permeability with the optimized microspheres fabricated using thiomers compared to conventional oral therapy. Pharmacokinetic investigations showed higher zidovudine plasma levels and Cmax with the administration of microspheres, particularly those composed of thiomers. The AUC0-24h values for thiomer microspheres were significantly greater than controls and chitosan microspheres, indicating improved oral bioavailability potential.
Conclusion: In conclusion, zidovudine-loaded thiomer-based mucoadhesive microspheres showed promising results with the ability to enhance the drug's oral bioavailability.
Graphical Abstract
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