An injectable in situ-forming gel (ISG) is a promising approach as a drug delivery system. In this study, natural resins including aloe, benzoin and propolis dissolved in N-methyl pyrrolidone (NMP) and dimethyl sulfoxide (DMSO) were investigated as ISG systems for their ability to form matrices in phosphate buffer. Regarding their functions as ISG, their pH values, viscosities, flow behaviours, surface tensions and injectabilities were tested. Benzoin and propolis exhibited greater matrix formation than aloe, owing to their higher resin contents. Benzoin and propolis in DMSO formed matrices with a faster solvent exchange rate compared with those in NMP. The former had a higher viscosity than the latter, but both of them exhibited similar densities and surface tensions. The 35% and 40% w/w benzoin in DMSO exhibited dominant matrix formations with acceptable injectability via syringe. The 35% w/w benzoin and propolis ISG in DMSO efficiently inhibited the growth of Staphylococcus aureus strains, and the propolis ISG also exhibited a clear inhibition zone against Porphyromonas gingivalis, whereas aloe did not. From the cell viability assay, propolis exhibited a higher toxicity against HCT116 colon cancer cells (IC50=95 µg/ml) compared with benzoin (IC50=400 µg/ml), whereas the resin from aloe showed no toxic effect on this cell. Due to their rapid insoluble matrix formation after contacting aqueous fluid as well as their antibacterial and cytotoxic activities against colon cancer cell, the 35% w/w benzoin and propolis in DMSO have the potential for use as a matrix former for ISGs.
Localized delivery systems have been typically designed to enhance drug concentration at a target site and minimize systemic drug toxicity. A rosin/cinnamon oil (CO) in situ forming gel (ISG) was developed for the sustainable delivery of imatinib mesylate (IM) against colorectal cancer cells. CO has been claimed to express a potent anticancer effect against various cancer cells, as well as a synergistic effect with IM on colorectal cancer cells; however, poor aqueous solubility limits its application. The effect of rosin with the adding CO was assessed on physicochemical properties and in vitro drug release from developed IM-loaded rosin/CO-based ISG. Moreover, in vitro cytotoxicity tests were conducted against two colorectal cancer cells. All formulations exhibited Newtonian flow behavior with viscosity less than 266.9 cP with easier injectability. The adding of CO decreased the hardness and increased the adhesive force of the obtained rosin gel. The gel formation increased over time under microscopic observation. CO-added ISG had a particle-like gel appearance, and it promoted a higher release of IM over a period of 28 days. All tested ISG formulations revealed cytotoxicity against HCT-116 and HT-29 cell lines at different incubation times. Thus, CO-loaded rosin-based ISG can act as a potentially sustainable IM delivery system for chemotherapy against colorectal cancer cells.
Cinnamon bark oil (CO) has anticancer activity in various type of cancer cells and could be used alternatively to support anticancer drugs. For the enhancement of cytotoxic effects, the combination of bioactive compounds with chemotherapeutics drug has been interested in the possibility of cancer treatment. This study aimed to determine whether there is a synergistic effect between the combination of CO and chemotherapeutic drug such as imatinib mesylate (IM) on HCT 116 and HT29 colorectal cancer cell lines. The cytotoxic activities of CO and IM were investigated individually and their combination in each cancer cell line using cell viability assay. The interaction between CO and IM was determined using the combination index (CI) method. Cinnamon bark oil exhibited the high cytotoxicity on HCT116 cell, while IM showed the high cytotoxic activity on HT 29 cell. The tested combination decreased notably viability of cell and allowed to reduce the dose of imatinib chemotherapy drug. The combination of CO with IM showed a strong synergistic effect (CI < 1) on HT29 cell. For HCT116 cell treated combination of CO (4μg/mL) and IM (10μg/mL) demonstrated a strong synergistic effect (CI = 0.52). Thus, the combined CO and IM might be applied for pharmaceutical drug delivery for colon cancer treatment.
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