Experimental Study On Ultrasound-guided Injection Of Paclitaxel-loaded Thermosensitive Hydrogel In Treatment Of Breast Cancer In Rats

ObjectiveTo prepare the sustained-release drug dilivery system of paclitaxel-loaded thermosensitive hydrogel, investigate the antitumor effect in the treatment of breast cancer by intratumoral injection, and probe a new method of minimally invasive therapy of breast cancer.Methods1. PLGA-PEG-PLGA copolymers were synthesized using successive ring opening polymerization. The molecular weight of copolymers was identified by means of gel permeation chromatography. The gelation temperature and in vitro release were determined.2. Established 50 rats model of breast cancer transplanted subcutaneously. Forty qualified rats were randomly divided into model group, blank gel group, paclitaxel group and paclitaxel-gel group, with 10 in each group. The ultrasound-guided intratumoral injection with physiologic saline, thermosensitive hydrogel, paclitaxel injection and paclitaxel-loaded thermosensitive hydrogel were given at a dose of 5 ml respectively.3. Regular ultrasound examination was undergone to observe and compare the differences of tumor size, internal echo and blood supply in groups after treatment.4. On day14 postinjection, animals were killed and the tumors were excised, weighted to evaluate the percent inhibition rate.5. Histological examinations of tumor tissues were undergone. TUNEL was taken to assay apoptosis index and RT-PCR to detect the expression changes in the poptosis-related genes of bcl-2 and bax. Results1. The synthetic copolymers possessed of uniform molecular weight distribution. The aqueous solutions of PLGA-PEG-PLGA polymers had reverse thermal gelation properties, which phase transition temperature (from liquid to hydrogel) of 23% was 28℃. Paclitaxel-loaded thermosensitive hydrogel released about 50% of paclitaxel in the first week, and continued to release drug for 3weeks.2. The tumors of model group and blank gel group were significantly increased after treatment, with inequality internal echo and relatively rich blood flow signals on ultrasound. The tumor growth was slower in paclitaxel group,while those in paclitaxel-gel group were mildly increased after treatment, with a small amount of significantly decreased blood flow signals detected in the surrounding. No complications such as hemorrhage, skin rupture or infection was found in either group.3. Intratumoral injection treatment of paclitaxel-loaded thermosensitive hydrogel displayed a mighty antitumor effect on breast cancer in rats, and the tumor inhibitory rate reached 62.77%, higher than that of blank gel group (3.53%) and paclitaxel group (36.27%) (P<0.05).4. Extensive necrosis of tumor tissue was found in the histopathologic examination of paclitaxel-gel group. The apoptosis index (39.22±5.69)% was higher than that of paclitaxel group (14.37±2.31)% (P<0.05). Down-regulation in bcl-2 mRNA expression was found, which was lower than that of paclitaxel group, while up-regulation in bax expression, higher than that of paclitaxel group (P<0.05). ConclusionUltrasound-guided local injection treatment of paclitaxel-loaded thermosensitive hydrogel displayed a mighty antitumor effect on breast cancer in rats. The efficacy on inhibiting proliferation and inducing apoptosis of this method was superior to the local injection of simple paclitaxel. It was easily operated and with safety. This new method of breast cancer treatment has potential clinical value.