Temperature-Ion-pH Triple Responsive Gellan Gum as In Situ Hydrogel for Long-Acting Cancer Treatment

Abstract

Background: Promising cancer chemotherapy requires the development of suitable drug delivery systems (DDSs). Previous research has indicated that a hydrogel is a powerful DDS for tumor therapy and holds great potential to offer a feasible method for cancer management. Methods: In this study, glutathione-gellan gum conjugate (GSH-GG) was synthesized through chemical reaction. Doxorubicin hydrochloride (DOX) was loaded into GSH-GG to accomplish DOX-loaded GSH-GG. The properties, injectability, drug release, and in vitro and in vivo anticancer effects of DOX-loaded GSH-GG were tested. Results: DOX-loaded GSH-GG showed a temperature-ion dual responsive gelling property with good viscosity, strength, and injectability at an optimized gel concentration of 1.5%. In addition, lower drug release was found under acidic conditions, offering beneficial long-acting drug release in the tumor microenvironment. DOX-loaded GSH-GG presented selective action by exerting substantially higher cytotoxicity on cancer cells (4T1) than on normal epithelial cells (L929), signifying the potential of complete inhibition of tumor progression, without affecting the health quality of the subjects. Conclusions: GSH-GG can be applied as a responsive gelling material for delivering DOX for promising cancer therapy.

Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect

“…In our previous study, we prepared glutathione-gellan gum (GSH-GG) . Initially, the prepared DOX&Lipos were dialyzed for 30 min using the 5% glucose solution, which can form the Lipos with calcium ions inside and no calcium ions outside.…”

“…In our previous study, we prepared glutathione-gellan gum (GSH-GG). 27 Initially, the prepared DOX&Lipos were dialyzed for 30 min using the 5% glucose solution, which can form the Lipos with calcium ions inside and no calcium ions outside. Afterward, GSH-GG was added dropwise to the freshly dialyzed Lipos and the mixture was stirred magnetically at room temperature for 30 min using the magnetic stirrer (SY18-type 1, Sile Instrument Co., Ltd., Shanghai, China).…”

“…26 Glutathione-gellan gum (GSH-GG), obtained by modifying GG with glutathione (GSH), not only retains the ionic-responsive and pH-responsive drug release of GG itself but also reduces the gel temperature of GG. 27 Lipos, due to their structural characteristics, offer several advantages over other nanocarriers. They possess the capacity to transport both hydrophobic and hydrophilic drugs, display biocompatibility, and show high encapsulation efficiency.…”

“…However, the hydrogel formed by GG often suffers from poor mechanical strength and high gelation temperatures, which severely limits their biomedical applications . Glutathione-gellan gum (GSH-GG), obtained by modifying GG with glutathione (GSH), not only retains the ionic-responsive and pH-responsive drug release of GG itself but also reduces the gel temperature of GG …”

Long-Acting Gel Formulations: Advancing Drug Delivery across Diverse Therapeutic Areas

“…For cancer treatment, the creation of long-acting gels is vital for enhancing the efficacy of treatments and reducing adverse effects. Notably, there is a concerted effort to amplify the anti-cancer properties of drugs such as tamoxifen and to craft controlled release mechanisms that offer localized and prolonged therapy for cancer patients [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”