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

被引:10
作者
Sripetthong, Sasikarn [1 ,2 ]
Nalinbenjapun, Sirinporn [1 ,2 ]
Basit, Abdul [1 ,2 ]
Surassmo, Suvimol [3 ]
Sajomsang, Warayuth [3 ]
Ovatlarnporn, Chitchamai [1 ,2 ]
机构
[1] Prince Songkla Univ, Fac Pharmaceut Sci, Dept Pharmaceut Chem, Hat Yai 90112, Thailand
[2] Prince Songkla Univ, Fac Pharmaceut Sci, Drug Delivery Syst Excellent Ctr, Hat Yai 90112, Thailand
[3] Natl Sci & Technol Dev Agcy, Natl Nanotechnol Ctr, Nanodelivery Syst Lab, Thailand Sci Pk, Pathum Thani 12120, Thailand
关键词
nano-micelles; quarternized chitosan-vanillin conjugate; curcumin; cisplatin; lung cancer; cytotoxicity evaluation; LUNG-CANCER; CARBOXYMETHYL CHITOSAN; CELLS; BIOAVAILABILITY; STRATEGIES; RESISTANCE; QUERCETIN; APOPTOSIS;
D O I
10.3390/jfb14100525
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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 ((HNMR)-H-1), 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 degree celsius 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 mu M as the IC50 value, in comparison to the treatment with cisplatin alone (14.22 +/- 1.01 mu M). 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.
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页数:28
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