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

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.

Liposome Loaded Ion/Temperature Dual Responsive Gellan Gum Hydrogel as Potential Nasal-To-Brain Delivery System.

Intranasal administration, which can bypass the blood-brain barrier (BBB), is widely recognized as a promising strategy for high-efficiency drug delivery to the brain. Herein, for the purpose of effectively delivering drugs to the brain via intranasal administration, glutathione (GSH)-modified gellan gum (GSH-GG) with ion/temperature dual responsive properties was synthesized and encapsulated on galanthamine hydrobromide (GH)-loaded liposomes (GH-Lipo) for effective GH delivery to the brain (GH-Lipo@GSH-GG). Our results demonstrated that GSH-GG greatly decreased the gelation temperature of GG from 44.0 °C to 22.1 °C without compromising its ion responsiveness. Moreover, GSH-GG had a good protection ability for GH-loaded liposomes without affecting its drug release. Most importantly, the finally obtained GH-Lipo@GSHGG showed acceptable targeted delivery of GH to the brain upon in vivo administration. Therefore, this formulation can be employed as a potential delivery system in nasal-to-brain delivery.