Abstract
Background:
Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible polymer widely used in drug delivery systems and tissue engineering applications. However, modifying PLGA with hydrophilic polymers can further enhance drug encapsulation and release characteristics.

Purpose:
This study aimed to develop and evaluate PLGA nanoparticles modified with chitosan and carboxymethyl chitosan (CMCh) to enhance drug release behavior using diclofenac sodium (DS) as a model drug.

Materials and Methods:
PLGA/DS nanoparticles were prepared using the double emulsion (water/oil/water) solvent evaporation technique. The nanoparticles were modified with chitosan and CMCh to improve encapsulation efficiency and drug release performance. Characterization studies were conducted using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) to assess drug–polymer interactions, while morphology was analyzed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM).

Results:
The incorporation of chitosan and CMCh significantly improved encapsulation efficiency and drug loading capacity of the nanoparticles. The modified nanoparticles demonstrated enhanced drug release at pH 6.8 and minimal release at pH 1.2, indicating pH-responsive behavior. ATR-FTIR analysis confirmed non-covalent interactions between diclofenac sodium and the polymer matrix. TEM and SEM studies revealed spherical nanoparticles with uniform morphology. Among the various formulations, nanoparticles with a chitosan-PLGA-DS and CMCh-PLGA-DS ratio of 2:20:4 were identified as the optimal formulation, providing the desired release profile.

Conclusions:
Surface modification of PLGA nanoparticles with chitosan and carboxymethyl chitosan effectively enhances drug encapsulation and controlled release behavior. The optimized nanoparticle system shows strong potential as an alternative drug delivery platform for diclofenac sodium.