Influnce of drug-polymer interactions on release kinetics of PLGA and PLAPEG Nanoparticles

Achieving nano-sized drug delivery systems (NDDS) has become a crucial topic in the medical field. Among the different approaches for controlled release, nanoparticles (NPs), nanofibers (NFs) and nanorods (NRs) stand out which, through nano-structural tailoring, can be improved for drug release in the body. Thus, NDDS are valuable alternatives to conventional antimicrobial and cancer treatments (1). Especially, among NPs, polymeric NPs arise as promising systems due to their advantages such as enhanced drug encapsulation efficiency and sustained release. However, designing polymeric NPs is still challenging since obtaining biodegradability while having a low degradation profile is not trivial. Poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid)/poly(ethylene glycol) (PLA/PEG) fulfill the former requirements and are suitable candidates. Since PLGA has favourable degradation kinetics and high hydrophobicity, making it ideal for hydrophobic drugs, while PLA/PEG combines hydrophobicity/hydrophilicity presenting improved adaptability for hydrophilic drugs and enhanced bloodstream circulation. In this study, PLGA and PLA/PEG NPs were synthesized using microfluidics and loaded with curcumin (CURC), a hydrophobic drug with anticancer, antimicrobial, and anti-inflammatory properties (2). The main objective was to evaluate how polymer composition affects hydrodynamic properties and drug-polymer interactions. For that, PLGA NPs with a mean size of 121.4 ± 1.32 nm (PDI of 0.245 ± 0.01) and PLA/PEG NPs of 42.3 ± 0.95 nm (PDI of 0.192 ± 0.04), were synthesized. Upon CURC loading, sizes increased to 153.3 ± 2.42 nm for PLGA and 47.3 ± 0.32 nm for PLA/PEG while as PDI’s 0.221 ± 0.02 and 0.249 ± 0.02. The encapsulation efficiency of CURC in PLGA NPs was an outstanding 65.8% ± 0.45, whereas PLA/PEG NPs had only 13.6% ± 0.75, showing the difficulty of loading hydrophobic drugs into hydrophilic NPs. According to the release profiles, PLGA NPs showed an initial burst release of ~30% in the first hour, followed by sustained release reaching 50% at 3 hours and 93% after 24 hours, however, PLA/PEG NPs released ~75% of CURC within the first hour, indicating a significantly faster release. These variations in drug release kinetics are influenced by polymer hydrophobicity, crystallinity, molecular weight, and degradation rates. Cytotoxicity tests on adeno-carcinomic human alveolar basal epithelial cells (A549) displayed IC50 values of 4.7 µg/mL for PLGA NPs and 4.8 µg/mL for PLA/PEG NPs. Overall, these findings highlight the important role of polymer composition in controlling drug delivery applications for the biomedical field.