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In this work, biodegradable PCL–PEG–PCL (PCEC) triblock copolymers were successfully synthesized at one-step. Aqueous solution of PCEC copolymer displayed thermosensitive sol–gel–sol transition behavior, which is flowing sol at low temperature and turns into non-flowing gel at body temperature. The cytotoxicity of PCEC copolymer was evaluated by cell viability assay using HEK293 and WISH cells. In vivo gel-formation, degradation test, acute toxicity tests, and histopathological study of PCEC hydrogels were performed in BALB/c mice by subcutaneous administration. In acute toxicity test, the mice were observed continuously for 21 days. For histopathologic study, samples including heart, liver, spleen, lung, kidneys, and tissue of injection site were histochemical prepared and stained with hematoxylin–eosin. No mortality or significant signs of acute toxicity was observed during the whole observation period and there is no significant lesion to be shown in histopathologic study of major organs and tissue of injection site. The maximum tolerance dose (MTD) of PCEC hydrogel (20 wt%) by subcutaneous administration was calculated to be higher than 25 g/kg b.w. The results indicated that the obtained PCEC hydrogel was non-toxic after subcutaneous administration, and could be a safe candidate for in situ gel-forming controlled drug delivery system. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4684–4694, 2009 [ABSTRACT FROM AUTHOR]

In this article, biodegradable and low molecular weight poly(ethylene glycol)–poly(ℇ-caprolactone)–poly(ethylene glycol) (PEG–PCL–PEG, PECE) triblock copolymers were successfully synthesized. Aqueous solution of the obtained PECE copolymers underwent sol–gel–sol transition as temperature increased which was flowing sol at room temperature and then turned into nonflowing gel at body temperature. Sol–gel–sol phase transition behaviors of aqueous PECE solutions were studied using rheometry and test tube-inverting method, which were affected by many factors, including the heating/cooling procedure and different additives in copolymers aqueous solution. In vitro drug release behavior was studied using bovine serum albumin (BSA) and Vitamin B12 (VB12) as model drugs, and the PECE hydrogel could protect BSA from acidic degradation for 1 week at least. Therefore, PECE hydrogel is believed to be promising for injectable in situ gel-forming controlled drug delivery system due to their great thermosensitivity and biodegradability. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3707–3717, 2009 [ABSTRACT FROM AUTHOR]