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Achieving High Drug Loading and Sustained Release of Hydrophobic Drugs in Hydrogels through In Situ Crystallization
Author(s) -
Ci Tianyuan,
Shen Yuning,
Cui Shuquan,
Liu Ruili,
Yu Lin,
Ding Jiandong
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201600299
Subject(s) - self healing hydrogels , crystallization , copolymer , drug , ethylene glycol , chemistry , aqueous solution , drug carrier , drug delivery , glycolic acid , lactic acid , chemical engineering , in vivo , controlled release , polymer chemistry , organic chemistry , pharmacology , polymer , medicine , microbiology and biotechnology , biology , bacteria , engineering , genetics
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.