Preparation of Self-Assembled, Curcumin-Loaded Nano-Micelles Using Quarternized Chitosan–Vanillin Imine (QCS-Vani Imine) Conjugate and Evaluation of Synergistic Anticancer Effect with Cisplatin

Author:

Sripetthong Sasikarn12ORCID,Nalinbenjapun Sirinporn12ORCID,Basit Abdul12ORCID,Surassmo Suvimol3,Sajomsang Warayuth3ORCID,Ovatlarnporn Chitchamai12ORCID

Affiliation:

1. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai 90112, Thailand

2. Drug Delivery System Excellent Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai 90112, Thailand

3. Nano-Delivery System Laboratory, National Nanotechnology Center, National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand

Abstract

Nano-micelles are self-assembling colloidal dispersions applied to enhance the anticancer efficacy of chemotherapeutic agents. In this study, the conjugate of quarternized chitosan and vanillin imine (QCS-Vani imine) was synthesized using the reaction of a Schiff base characterized by proton-NMR (1HNMR), UV-Vis spectroscopy, and FT-IR. The critical micelle concentration (CMC), particle size, and zeta potential of the resulting product were determined. The QCS-Vani imine conjugate was used as a carrier for the development of curcumin-loaded nano-micelles, and their entrapment efficiency (%EE), drug-loading capacity (%LC) and in vitro release were investigated using HPLC analysis. Moreover, the nano-micelles containing curcumin were combined with various concentrations of cisplatin and evaluated for a possible anticancer synergistic effect. The anticancer activity was evaluated against lung cancer A549 and mouse fibroblast L929 cell lines. The percent yield (%) of the QCS-Vani imine conjugate was 93.18%. The curcumin-loaded QCS-Vani imine nano-micelles were characterized and found to have a spherical shape (by TEM) with size < 200 nm (by DLS) with high %EE up to 67.61% and %LC up to 6.15 ± 0.41%. The loaded lyophilized powder of the nano-micelles was more stable at 4 °C than at room temperature during 120 days of storage. pH-sensitive release properties were observed to have a higher curcumin release at pH 5.5 (cancer environment) than at pH 7.4 (systemic environment). Curcumin-loaded QCS-Vani imine nano-micelles showed higher cytotoxicity and selectivity toward lung cancer A549 cell lines and exhibited lower toxicity toward the normal cell (H9C2) than pure curcumin. Moreover, the curcumin-loaded QCS-Vani imine nano-micelles exhibited an enhanced property of inducing cell cycle arrest during the S-phase against A549 cells and showed prominently induced apoptosis in lung cancer cells compared to that with curcumin. The co-treatment of cisplatin with curcumin-loaded QCS-Vani imine nano-micelles presented an enhanced anticancer effect, showing 8.66 ± 0.88 μM as the IC50 value, in comparison to the treatment with cisplatin alone (14.22 ± 1.01 μM). These findings suggest that the developed QCS-Vani imine nano-micelle is a potential drug delivery system and could be a promising approach for treating lung cancer in combination with cisplatin.

Funder

National Science, Research and Innovation Fund

Thailand Graduate Institute of Science and Technology Scholarship

Graduate School Prince of Songkla University

Publisher

MDPI AG

Subject

Biomedical Engineering,Biomaterials

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