Thermosensitive Chitosan-Based Injectable Hydrogel as an Efficient Anticancer Drug Carrier

Abstract

A thermosensitive, physically cross-linked injectable hydrogel was formulated for the effective and sustained delivery of disulfiram (DSF) to the cancer cells as there is no hydrogel formulation available until now for the delivery of DSF. As we know, hydrogels have an advantage over other drug delivery systems because of their unique properties, so we proposed to formulate an injectable hydrogel system for the sustained delivery of an anticancer drug (DSF) to cancer cells. To investigate the surface morphology, a scanning electron microscope study was carried out, and for thermal stability of hydrogels, TGA (thermogravimetric analysis) and DSC (differential scanning calorimetry) were performed. The rheological behavior of hydrogels was evaluated with the increasing temperature and time. These developed hydrogels possessing excellent biocompatibility could be injected at room temperature following rapid gel formation at body temperature. The swelling index and in vitro drug release studies were performed at different pH (6.8 and 7.4) and temperatures (25 and 37 °C). The cell viability of the blank hydrogel, free DSF solution, and Ch/DSF (chitosan/DSF)-loaded hydrogel was studied by MTT assay on SMMC-7721 cells for 24 and 48 h, which exhibited higher cytotoxicity in a dose-dependent manner in contrast to the free DSF solution. Moreover, the cellular uptake of DSF-loaded hydrogels was observed stronger as compared with free DSF. Hence, chitosan-based hydrogels loaded with DSF possessing exceptional properties can be used as a novel injectable anticancer drug for the sustained delivery of DSF for long-term cancer therapy.

A Drug Release Mechanism Controlled by Hydrophobic/Hydrophilic Balance of the Matrix. Theoretical and Experimental Perspectives

“…The formulations displayed a porous morphology, with interconnected pores which assure favorable sink conditions of the drug (Figure 2). Moreover, the scanning electron microscopy (SEM) images confirmed the POM observations, indicating no sub-micrometric crystals into the pores or on the pore walls, suggesting a good dispersion of the drug into the matrix [35,36].…”

“…It can be observed that the progressive increase of the hydrophilic component into formulation lead to the fastening of the drug release. Thus, the simple manipulation of the hydrophobic/hydrophilic balance can tune the drug release in agreement with the addressed requirement [9,[35][36][37]. Quantitatively speaking, in 7 days the CP4B2.5D sample released more than 99% from the entire amount of the encapsulated DCF, while the sample CP5B1.5D released only 91% (Figure 3).…”

Analysis on Efficacy of Chitosan-Based Gel on Bone Quality and Quantity

“…Chitosan has favorable properties including biocompatibility, biodegradability, antibacterial, and biological activity, as well as its renewable character. Some studies reported that creating a chitosan in hydrogel form would provide a good environment for encapsulation and localized delivery of cells and cell proliferation (Shariatinia and Jalali, 2018;Ahsan et al, 2020). Additionally, the hydrogel would make chitosan respond to various stimuli for example, temperature, heat, light, pH, ionic strength, humidity, and redox potential that are playing an important role for biomedical applications such as drug delivery and tissue engineering (Hu et al, 2017).…”

Review of Applications and Future Prospects of Stimuli-Responsive Hydrogel Based on Thermo-Responsive Biopolymers in Drug Delivery Systems

“…The thermosensitive nasal formulations showed in situ gelation with desirable spray characteristics at room temperature, and the muco-adhesive behavior of the semi-solid at physiological temperature due to phase change rendered potential to efficiently deliver therapeutics to brain [ 52 ]. The physically cross-linked injectable thermo-responsive hydrogel of chitosan was developed for the effective and sustained delivery of disulfiram to the cancer cells and these gel systems showed excellent biocompatibility and cytotoxicity in a dose-dependent manner on SMMC-7721 cells [ 53 ]. The formulation injected at room temperature followed rapid gel formation at body temperature and showed stronger cellular uptake than free disulfiram [ 53 ].…”

“…The physically cross-linked injectable thermo-responsive hydrogel of chitosan was developed for the effective and sustained delivery of disulfiram to the cancer cells and these gel systems showed excellent biocompatibility and cytotoxicity in a dose-dependent manner on SMMC-7721 cells [ 53 ]. The formulation injected at room temperature followed rapid gel formation at body temperature and showed stronger cellular uptake than free disulfiram [ 53 ]. The thermo-responsive hydrogel developed with chitosan and α (alpha) β -glycerophosphate showed sol–gel transition at 37 °C and was applied as drug delivery system for the sustained release of adriamycin and 6-mercaptopurine [ 54 ].…”