pH triggered injectable amphiphilic hydrogel containing doxorubicin and paclitaxel

• Published in: International journal of pharmaceutics 2011-05, Vol.410 (1), p.83-91
• Main Authors: Zhao, Lingling, Zhu, Lijun, Liu, Fuyong, Liu, Chenyang, Shan-Dan, Wang, Qian, Zhang, Chengliang, Li, Jiaoli, Liu, Jiguang, Qu, Xiaozhong, Yang, Zhenzhong
• Format: Article
• Language: English
• Subjects: animal models; Animals; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - toxicity; Antitumor activity; benzaldehyde; Biological and medical sciences; blood circulation; Cardiotoxicity; chitosan; Chitosan - chemistry; Combination delivery; doxorubicin; Doxorubicin - administration & dosage; Drug Carriers - chemistry; Drug Delivery Systems; drug therapy; ethylene glycol; Female; gelation; gels; General pharmacology; growth retardation; hydrocolloids; Hydrogels; Hydrogen-Ion Concentration; hydrophilicity; Hydrophobic and Hydrophilic Interactions; hydrophobicity; Injectable gel; Medical sciences; Melanoma, Experimental - drug therapy; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; paclitaxel; Paclitaxel - administration & dosage; pH triggered; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; propylene glycol; Rheology; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Survival Rate; Time Factors
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.03.034

Injectable hydrogel with hydrophobic microdomains for incorporating both hydrophilic and hydrophobic drugs, herein doxorubicin hydrochloride (DOX) and paclitaxel (PTX), was synthesized through dynamic bonding of glycol chitosan and benzaldehyde capped poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) via Schiff's reaction triggered by environmental pH. Rheology tests show that the inclusion of hydrophilic drug decreases the gelation time and gains more robust gel, while the addition of hydrophobic drug has opposite influences. Dual-drug release from the DOX + PTX loaded gels was observed and the release rate can be accelerated by decreasing the environmental pH from physiological (7.4) to weak acidic pH (6.8). In vivo investigation proved that the gels were able to diminish the amount of DOX in blood circulation and limit the DOX-induced cardiotoxicity. By intratumoral administration, the hydrogel-drug formulations resulted in efficient growth inhibition of subcutaneous tumor (B16F10) on C57LB/6 mouse model. The advantage of the current system for DOX + PTX combination therapy was demonstrated by a prolongation of survival time in comparison with the single drug therapy.