PLGA encapsulated γ-cyclodextrin-meropenem inclusion complex formulation for oral delivery

Area of Science:

• Biomaterials Science
• Pharmaceutical Sciences
• Nanotechnology

Background:

• Meropenem (MER) is a critical antibiotic for resistant bacterial infections.
• Clinical use of MER is limited by its instability in aqueous solutions and gastric environments, and short plasma half-life.
• Novel drug delivery systems are needed to overcome MER's limitations.

Purpose of the Study:

• To develop a multi-material delivery system for meropenem (MER) using gamma-cyclodextrin (γ-CD) and poly lactic-co-glycolic acid (PLGA).
• To enhance MER's stability, control its release, and maintain its antibacterial activity.
• To overcome challenges associated with MER's chemical instability and short plasma half-life.

Main Methods:

• Formation of MER-γ-CD inclusion complex using a liquid CO2 method.
• Encapsulation of MER-γ-CD into PLGA nanoparticles (MER-γ-CD NPs) via double emulsion solvent evaporation.
• Characterization of inclusion complex and nanoparticles using FTIR, XRD, DSC, SEM, 1H NMR, and DLS.
• In vitro release studies and apparent permeability coefficient (Papp) measurements.
• Assessment of antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa.

Main Results:

• Successful formation of MER-γ-CD inclusion complex and MER-γ-CD NPs confirmed by multiple characterization techniques.
• Drug loading and entrapment efficiency for MER-γ-CD were 21.9% and 92.2%, respectively; for MER-γ-CD NPs, they were 3.6% and 42.1%.
• In vitro release showed controlled release of MER from NPs, with 23.6% active drug released in 8 hours.
• Apparent permeability coefficients indicated no significant negative impact of the delivery system on drug transport.
• MER-γ-CD NPs retained significant antibacterial activity against S. aureus and P. aeruginosa.

Conclusions:

• The developed MER-γ-CD NPs effectively protect meropenem from degradation by gastric pH.
• The nanoparticle system offers controlled drug release, potentially improving therapeutic outcomes.
• MER-γ-CD NPs maintain the essential antibacterial efficacy of meropenem, presenting a promising strategy for treating resistant infections.