Folate and Borneol Modified Bifunctional Nanoparticles for Enhanced Oral Absorption

Area of Science:

• Nanotechnology
• Pharmaceutics
• Drug Delivery

Background:

• Oral drug administration is preferred for convenience and patient compliance.
• Docetaxel (DTX) has poor oral bioavailability, limiting its therapeutic use.
• Developing effective oral delivery systems for DTX is crucial.

Purpose of the Study:

• To design and evaluate novel nanoparticles for enhanced oral absorption of docetaxel (DTX).
• To investigate the targeting and absorption mechanisms of the developed nanoparticles.
• To assess the pharmacokinetic profile and safety of the oral formulation.

Main Methods:

• Docetaxel (DTX) loaded polylactic-co-glycolic acid (PLGA) nanoparticles were formulated and coated with polyethyleneimine-folic acid (PEI-FA) and polyethyleneimine-borneol (PEI-BO).
• Nanoparticle characterization included size, encapsulation efficiency (EE%), and drug loading (DL%).
• In vitro release studies, reverted gut sac method, cellular uptake assays, and pharmacokinetic studies were performed.

Main Results:

• FA/BO-PLGA-NPs exhibited spherical morphology with an average size of 137.0 nm, EE% of 80.3%, and DL% of 2.3%.
• In vitro release showed 62.1% DTX release at pH 7.4.
• Intestinal absorption was 6.0 times higher than DTX alone, with enhanced cellular uptake via FA-mediated targeting and BO-mediated P-gp inhibition.
• Oral administration of FA/BO-PLGA-NPs resulted in a 6.8-fold increase in DTX bioavailability compared to DTX suspension.
• The formulation showed no significant intestinal irritation.

Conclusions:

• The developed FA/BO-PLGA-NPs effectively enhance the oral absorption and bioavailability of docetaxel (DTX).
• The formulation utilizes active targeting and P-gp inhibition for improved drug delivery.
• FA/BO-PLGA-NPs represent a promising strategy for oral drug delivery, particularly for poorly absorbed drugs like DTX.