Enhancing Doxorubicin Efficacy with a Novel Lipid-Polymer Nanosystem Containing Melatonin: Formulation, Characterization and in Vitro Study
摘要
Recently, combination therapy for cancer has been shown to be more effective than monotherapy, resulting in reduced side effects and increased treatment efficacy. Melatonin, a naturally produced hormone, exhibits anticancer properties by inducing apoptosis and modulating the immune system; however, its short half-life and variable bioavailability limit its effectiveness. The current research examines how melatonin-chitosan-phosphatidylcholine nanoparticles (Cht-Pc/MLT NPs), as a novel lipid-polymer nanosystem, could enhance the anticancer properties of doxorubicin (DOX) against colorectal cancer cell lines (C26).
MethodsThe Cht-Pc/MLT NPs were synthesized using the self-assembly method. The formulations’ physicochemical characterizations, including particle size, stability, and release profile, were investigated. The cytotoxicity evaluation was conducted independently and with free DOX on the C26 cell line using the MTT and sub-G1 assays.
ResultsThe optimal formulation displayed a size of 173 ± 18.17 nm, a surface charge of 16.28 mV, encapsulation efficiency and loading capacity of 63.148% and 30.861%, respectively. It was observed that the release of MLT from the NPs in simulated gastric fluid (SGF, pH 1.2) was minimal during the initial 4 h, making it suitable for oral administration. On the other hand, in intestinal fluid (SIF, pH 6.8), about 30% of MLT was released within the first 4 h, and at the end of 48 h, the release reached 45%. The observed changes in particle size after three months of storage at 4 °C were negligible obtained. Our research demonstrated that the combined delivery of DOX and Cht-Pc/MLT NPs significantly enhanced the cytotoxicity of colorectal cancer cells (C26) compared to other groups.
ConclusionThe results indicate that this designed combination treatment system may be applicable in chemotherapy protocols.