title: Achieving High Drug Loading and Sustained Release of Hydrophobic Drugs in Hydrogels through In Situ Crystallization.
abstract: Inadequate drug loading of hydrophobic drugs is a classic problem when hydrogels are utilized as sustained-release carriers of drugs. Herein, a strategy to load plenty of hydrophobic drugs is presented. The antitumor drug 10-hydroxycamptothecin in the thermogel of poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) is employed. The drug is soluble in an alkaline medium, yet insoluble in a neutral/acidic medium. The crystallization is triggered after adding an alkaline drug solution into an acidic copolymer solution. The concentrated copolymer aqueous solution undergoes a sol-gel transition upon heating, faster than the crystallization. As a result, plenty of evenly dispersed drug microcrystals are formed. The in vitro and in vivo experiments indicate both high drug loading and sustained release with enhanced antitumor efficacy and reduced adverse effects. The system resolves the challenge in formulation of hydrophobic drugs in hydrogels, and is stimulating for encapsulating drugs with a soluble-insoluble transition into a material environment.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai, 200433, China.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Ci
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai, 200433, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai, 200433, China.
authors.forename: Shuquan
authors.initials: S
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai, 200433, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai, 200433, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai, 200433, China.|Key Laboratory of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Ding
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003460:Crystallization; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000627:therapeutic use; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D019344:Lactic Acid; D011092:Polyethylene Glycols; C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: 10-hydroxycamptothecin; drug delivery systems; hydrogels; microcrystals; thermogels