title: pH triggered injectable amphiphilic hydrogel containing doxorubicin and paclitaxel.
abstract: 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.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhao
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhu
authors.forename: Fuyong
authors.initials: F
authors.lastname: Liu
authors.forename: Chenyang
authors.initials: C
authors.lastname: Liu
authors.lastname: Shan-Dan
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Chengliang
authors.initials: C
authors.lastname: Zhang
authors.forename: Jiaoli
authors.initials: J
authors.lastname: Li
authors.forename: Jiguang
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Qu
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D048271:Chitosan / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000737:chemistry; D012212:Rheology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; C118638:glycol-chitosan; D011092:Polyethylene Glycols; D004317:Doxorubicin; D048271:Chitosan; D017239:Paclitaxel