Design and characterization of α-linolenic acid-grafted Poly(β-Amino ester) nanocarriers for drug delivery


Kaplan O., BAL K., Celik S. K., Tosun N. G., GÖK M. K.

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.120, 2026 (SCI-Expanded, Scopus) identifier identifier

Özet

In this study, a novel pH-sensitive and biocompatible alpha-linolenic acid (ALA)-grafted poly (beta-amino ester) (P beta AE) was developed for anticancer applications. ALA was selected to support the anticancer efficacy of the system, given its known biological activities, as well as the stability and cellular-interaction potential it confers on the polymer due to its long-chain, hydrophobic structure. The modification was carried out using the DCC-mediated amidation method between the terminal amine groups of P beta AE and the carboxyl groups of ALA. The formation of amide bonds was confirmed by FTIR, 1H NMR and 13C NMR analyses, while GPC and DSC were employed to evaluate the molecular weight distribution and thermal behavior of the synthesized polymers, respectively. Curcumin (CUR)-loaded nanoparticles were prepared as a model drug by nanoprecipitation. Stability studies of the resulting P beta AE-CUR and P beta AEALA-CUR nanoparticles demonstrated that ALA preserved the structural integrity of the grafted system and reduced its tendency to aggregate. Release studies conducted under physiological (pH 7.4) and acidic (pH 5.0) conditions revealed that both systems exhibited pH-sensitive behavior, with a significantly higher release rate in acidic environments, whereas a slower, more controlled release profile was observed under physiological conditions. In cell culture assays, P beta AEALA-CUR nanoparticles exhibited higher cytotoxicity toward cancer cells (HeLa and HT29) and biocompatibility in healthy fibroblast cells (BJ). These results demonstrate that the ALA-grafted P beta AE polymer offers an innovative nanocarrier system with enhanced structural stability, selective anticancer activity, and pH-sensitive release behavior.