Development and physicochemical characterization of copper complexes-loaded PLGA nanoparticles

Area of Science:

• Materials Science
• Nanotechnology
• Radiopharmaceutical Chemistry

Background:

• Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are widely investigated for drug delivery and biomedical applications due to their biocompatibility and biodegradability.
• Developing stable and well-characterized nanoparticles is crucial for their effective use, particularly in advanced applications like Positron Emission Tomography (PET) imaging.
• Encapsulation of metal complexes within nanoparticles requires careful control over formulation parameters to ensure high efficiency and desired particle characteristics.

Purpose of the Study:

• To systematically investigate and optimize the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles using a modified water-in-oil-in-water (W/O/W) emulsion solvent diffusion method.
• To characterize the influence of independent processing parameters on nanoparticle properties such as size, polydispersity, and surface morphology.
• To evaluate the optimized PLGA nanoparticle formulation for the encapsulation of copper complexes (Cu-cyclen and Cu-DOTA) as potential PET imaging agents.

Main Methods:

• Preparation of PLGA nanoparticles via a modified W/O/W emulsion solvent diffusion technique utilizing fully biocompatible and biodegradable components.
• Systematic study of independent processing parameters, including the lactide-to-glycolide (L:G) ratio of PLGA, diffusion phase composition, and hydroxyl ion concentration.
• Characterization of nanoparticles using Dynamic Light Scattering (DLS) for particle size, polydispersity, and zeta-potential, and Transmission Electron Microscopy (TEM)/Atomic Force Microscopy (AFM) for surface morphology.

Main Results:

• Key formulation factors identified: L:G ratio of PLGA, nature of the diffusion phase, and presence of hydroxyl ions in the aqueous phase.
• Optimized PLGA nanoparticles achieved high preparation yields (>95%), particle sizes below 200 nm, and a low polydispersity index (<0.1).
• TEM analysis confirmed a narrow size distribution, spherical shape, and smooth surface of the prepared nanoparticles.
• Encapsulation efficiency for Cu-cyclen and Cu-DOTA complexes ranged between 20% and 25% using the optimized formulation.

Conclusions:

• The modified W/O/W emulsion solvent diffusion method allows for precise control over PLGA nanoparticle characteristics by regulating specific formulation parameters.
• The optimized PLGA nanoparticles exhibit favorable physicochemical properties suitable for biomedical applications, including potential use in PET imaging.
• The study successfully demonstrated the feasibility of encapsulating copper complexes within PLGA nanoparticles, paving the way for developing novel PET imaging agents.