Therapeutic effectiveness of slow-release PLGA-oxaliplatin microsphere on human colorectal tumor-bearing mice.
The aim was to develop a slow-release poly-lactic-coglycolic acid (PLGA)-oxaliplatin microsphere and to assess the therapeutic effectiveness and safety of this preparation on colorectal tumor in vivo. The PLGA-oxaliplatin microsphere was prepared based on a spray-drying method, and the drug loading and in-vitro oxaliplatin release profile were carried out using high performance liquid chromatography. The inhibiting effect on tumor growth was examined using in-vivo subcutaneously inoculated colorectal tumor models of nude mice. The size of the microsphere was less than 100 microm, drug loading was 18-22% and drug release time lasted as long as 30 days. PLGA-oxaliplatin microspheres significantly restrained tumor growth and this effect correlated with decreased expression of proliferating cell nuclear antigen and increased expression of terminal deoxynucleotidyltransferase dUTP nick end labeling in tumor cells. Bodyweight measurement and blood analysis did not suggest significant adverse effects on the mice during the study. The PLGA-oxaliplatin microsphere developed here was suitable for regional use; it appears safe and effective in controlling the tumor growth. This preparation shows promise in reducing local recurrence of colorectal cancer after resection, but needs further investigation.
Li
Jing-Quan
JQ
Chinese PLA General Hospital, Beijing.
Wang
Shi-Liang
SL
Xu
Fei
F
Liu
Zhao-Yang
ZY
Li
Rong
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D000077150:Oxaliplatin; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid