ABSTRACT
BACKGROUND:Ricin possesses strong cytotoxicity but lacks of specificity.Severe adverse reactions can be caused if ricin is systemically administered.Interstitial chemotherapy with ricin coated by a sustained-release carrier can enhance local therapeutic effects of tumor,avoiding systemic-toxic occurrence.OBJECTIVE:To prepare injectable and biodegradable thermosensitive poly(D,L-lactide-co-glycolide)(PLGA)-polyethylene glycol(PEG)-PLGA copolymer-based hydrogels and to observe the in vitro drug delivery of the PLGA-PEO-PLGA copolymer hydrogel as a sustained-release carrier of ricin.DESIGN,TIME AND SETTING:A controlled observation was performed at the Center for Medical Bioengineering.Fujian Medical University between August and December 2007.MATERlALS:Ricin with a purity of 95%was purified by Fuiian Institute of Ultrasonic Medicine.DL-lactide and L-glycolide were provided by Glycolide Lactide Co.,Ltd..China.METHODS:PLGA-PEG-PLGA-copolymer was synthesized by ring-opening polymerization.MAIN OUTCOME MEASURES:Phase transition temperature was determined by test tube turnover.relativemolecular mass by high-performance gel permeation chromatography,the proportion of block copolymer by nuclear magnetic resonance spectrometry.the in vitro drug delivery of ricin coated by PLGA-PEG-PLGA copolymcr hydrogelby enzyme linked immunosorbent assay.the structural integrity of released ricin by high-performance liquid chromatography,the cytotoxicity of released ricin by methyl thiazolyl tetrazolium assay.RESULTS:The synthesized copolymer PLGA-PEG-PLGA exhibited reverse.thermosensitivity.The phase transition temperature of the copolymer was 26℃at 230 g/L.The weight-average molecular weight and number-average molecular weight of this copolymer was 8 027 and 6 643,respectively,and the multiple-dispersion toefficient was 1.17.The block ratio for PEG and PLGA was 3:2.Drug-loaded PLGA-PEG-PLGA hydrogel could release ricin in vitro for a total of 18 successive days and simultaneously well maintain cytotoxicity and the structural stability of ricin.CONCLUSION:PLGA-PEG-PLGA copolymer is an ideal carrier for sustained delivery of ricin