Biotin functionalized chitosan nanoparticle containing L-carnosine as dry powder for inhalation

Le résumé fourni par la source

L-carnosine, a dipeptide, has attracted considerable attention for its potential anticancer properties. This study employed the ionic gelation method to prepare L-carnosine-loaded chitosan nanoparticles (CSNPs), which were subsequently surface-functionalized with biotin to enable targeted delivery to lung cancer cells. The resulting nanoparticles exhibited an average particle size of 244.5 ± 4.2 nm, a drug loading efficiency of 32 ± 2.32%, and a drug entrapment efficiency of 83.63 ± 0.23%, indicating effective drug dispersion within the polymer matrix. Surface functionalization was confirmed by attenuated total reflectance (ATR) spectroscopy and 1H NMR analysis, evidenced by the shifting of characteristic peaks, including the disappearance of a peak at 11.985 ppm and the emergence of a singlet at 7.492 ppm, confirming successful biotin conjugation. Cytotoxicity assessed by MTT assay on A-549 lung cancer cells demonstrated enhanced efficacy, with IC50 values of 152.4 ± 0.067 µg/mL for free L-carnosine, 133.8 ± 0.096 µg/mL for CSNPs, and 104.9 ± 0.12 µg/mL for biotin-functionalized CSNPs (BICSNPs). In vitro drug release studies showed sustained release profiles, with 84.54 ± 0.82% and 81.76 ± 0.99% drug release at 5 hours for CSNPs and BICSNPs, respectively. In vivo pharmacokinetic evaluation following pulmonary administration to male Wistar rats revealed improved bioavailability of the nanoparticle formulations, with maximum plasma concentrations (C_max) of 3.1386 ± 0.1744 µg/mL for CSNPs and 3.28083 ± 0.1398 µg/mL for BICSNPs. Corresponding area under the curve (AUC) values were significantly higher for CSNPs (26.783 ± 0.4817 µg/mL·h) and BICSNPs (29.0947 ± 1.125 µg/mL·h) compared to free L-carnosine (14.79295 ± 0.03605 µg/mL·h). Furthermore, BICSNPs were formulated into a dry powder inhalation system using inhalable-grade lactose, resulting in substantially enhanced lung deposition. Collectively, these findings suggest that biotin-functionalized L-carnosine-loaded chitosan nanoparticles hold significant promise as targeted carriers for lung cancer therapy via pulmonary delivery.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.