Abstract:

BACKGROUND: Under ultrasound guidance, intratumoral injection of sustained-released chemotherapeutics for tumor interstitial chemotherapy can improve antitumor and decrease systemic toxicity and side effects.
OBJECTIVE: To investigate the inhibitory effect of poly (lactic-co-glycolic acid) (PLGA) microspheres containing docetaxel intratumoral injection under ultrasound guidance on the proliferation of human triple negative breast cancer xenograft.
METHODS: Sustained-release PLGA microspheres containing docetaxel was prepared by solvent evaporation method. The morphology and particle size were observed by scanning electron microscope. The drug loading rate, entrapment efficiency and in vitro release were examined by high performance liquid chromatography. The human triple negative breast cancer-bearing nude mouse model was established and divided into five groups: model group (with no treatment), microspheres group (injected blank PLGA microspheres), docetaxel intratumoral injection group (injected 10 mg/kg docetaxel and administrated once every 10 days for 40 days continuously), PLGA microspheres containing docetaxel low-dose group (injected drug-released microspheres intratumorally: 20 mg/kg docetaxel one time) and PLGA microspheres containing docetaxel high-dose group (injected 40 mg/kg docetaxel one time)
RESULTS AND CONCLUSION: The mean particle size of prepared PLGA microspheres containing docetaxel was detected as 23.1 μm with an optimal entrapment efficiency of 96.3%, drug loading rate of 4.82%, and cumulative release drug rate of 85.7% within 40 days. Under ultrasound guidance, intratumoral injection of PLGA microspheres containing docetaxel displayed a potent antitumor effect on human triple negative breast cancer xenograft. And the tumor inhibition rate of the high-dose group had reached 65.7%. Color Doppler ultrasound showed the tumor blood supply was significantly decreased. Pathological examination indicated that the tumor tissues were found a great of putrescence. These findings suggest that interstitial chemotherapy by using ultrasound-guided intratumoral injection of PLGA microspheres containing docetaxel can significantly inhibit the proliferation of human triple negative breast cancer xenograft.