Injectable PLGA Adefovir microspheres; the way for long term therapy of chronic hepatitis-B

Area of Science:

• Pharmaceutical Sciences
• Biomaterials Science
• Hepatology

Background:

• Chronic hepatitis-B requires long-term antiviral therapy, often involving daily Adefovir dosing.
• Daily medication regimens can lead to poor patient compliance and treatment inconvenience.
• Poly-d,l-lactic-co-glycolic acid (PLGA) microspheres offer a potential solution for sustained drug delivery.

Purpose of the Study:

• To formulate and characterize sustained-release Adefovir Poly-d,l-lactic-co-glycolic acid (PLGA) microspheres.
• To evaluate the in vitro drug release and in vivo pharmacokinetic profile of the Adefovir-PLGA microspheres.
• To assess the potential of Adefovir-PLGA microspheres as a long-term treatment for chronic hepatitis-B.

Main Methods:

• Formulation of Adefovir-PLGA microspheres using varying drug:polymer ratios, polymer viscosity, and lactide content.
• Characterization included entrapment efficiency, particle size distribution, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC).
• In vitro drug release studies were conducted over extended periods (up to 90 days), and in vivo pharmacokinetic studies were performed in rats following intramuscular injection.

Main Results:

• Successful formulation of Adefovir-PLGA microspheres with entrapment efficiencies ranging from 55.83% to 86.95%.
• FTIR and DSC analyses indicated significant drug-polymer interactions, while SEM showed smooth, nonporous microsphere surfaces.
• In vitro release studies demonstrated sustained drug release over 90 days. In vivo studies showed a significant increase in Tmax, AUC0-t, and MRT, with a significant decrease in Cmax (p < 0.05).

Conclusions:

• Adefovir-PLGA microspheres are a viable sustained-release formulation for managing chronic hepatitis-B.
• The developed microspheres significantly prolong drug presence in the body compared to daily dosing.
• This formulation offers a promising alternative to daily Adefovir administration, enhancing patient convenience and potentially improving treatment outcomes.