Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design

Area of Science:

• Biotechnology
• Materials Science
• Pharmaceutical Sciences

Background:

• Advancements in biotechnology necessitate effective oral delivery systems for therapeutic and antigenic macromolecules.
• Existing oral delivery methods face challenges in delivering large biomolecules effectively.

Purpose of the Study:

• To develop and characterize a novel nanoparticle-in-microsphere oral delivery system (NiMOS).
• To investigate the influence of key formulation variables on the particle size of NiMOS.
• To establish a predictive model for NiMOS particle size.

Main Methods:

• Encapsulation of fluorescein isothiocyanate (FITC)-labeled gelatin nanoparticles within poly(epsilon-caprolactone) (PCL) microspheres using a double emulsion technique.
• Application of a 3(3) randomized full factorial design to study variables: polymer concentration, nanoparticle loading, and homogenization speed.
• Statistical analysis using multiple linear regression and Student's t-test.

Main Results:

• A statistical model was developed to predict NiMOS particle size based on formulation parameters.
• High polymer concentration and low homogenization speed favored larger NiMOS particles.
• High homogenization speed was crucial for achieving smaller NiMOS particles (<10 µm).
• Fluorescent microscopy confirmed successful encapsulation of gelatin nanoparticles within PCL microspheres.

Conclusions:

• The developed NiMOS system demonstrates potential for oral delivery of therapeutic and antigenic macromolecules.
• The predictive model allows for controlled fabrication of NiMOS with desired particle sizes.
• NiMOS particles under 10 µm are achievable, suitable for oral administration.