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.
Salak peel extract has various biological properties befitting cosmeceutical applications; however, their practical uses are still limited due to their low water solubility and stability. Encapsulation technology was employed to alleviate these issues. In this work, we presented a simple method to prepare ethosome-encapsulated salak peel extract using green solvents (ethanol and water). For this purpose, we used 95% ethanol to extract salak peel and explored its activities. Results showed that, in addition to anti-oxidant, the extract also showed anti-tyrosinase, anti-inflammatory, and anti-bacterial (against S. aureus) activities. These activities indicate its potential uses in cosmeceutical applications. We further encapsulated the extract in ethosomes using a stirrer and green solvents for the preparation methods. The yielded ethosomes exhibited a size range of 120 to 205 nm, polydispersity index (PDI) of 0.15 to 0.25, and zeta potential of −35 to −60 mV depending on the amount of L-α-phosphatidylcholine used. The highest encapsulation efficiency was approximately 30%. The antiradical capacity and anti-inflammatory activities of salak peel extract were also found to be maintained after the encapsulation process. An in vitro biocompatibility study of the extract after encapsulation was also performed. The results not only indicated good biocompatibility, but also the potential skin-rejuvenating ability of salak peel ethosomes. A stability study was also performed, and the results suggested that these ethosomes were stable at different conditions. With further investigation, salak peel ethosomes, as presented here, can be suitable for cosmeceutical applications.