Temozolomide/PLGA microparticles: a new protocol for treatment of glioma in rats.
Implantable and poly (d,l-lactide-co-glycolide) (PLGA) microparticles were developed to deliver temozolomide (TM) continuously in interstitial chemotherapy for glioma. The therapeutic effect of temozolomide/PLGA was evaluated in a rat C6 glioma model. C6 cells were implanted orthotopically into 100 rat brains in 5 groups (n=20 each): sham operation group, control group, local delivery of blank PLGA microspheres group, oral TM group, and local delivery of TM/PLGA group. Rats in oral TM group were orally administered temozolomide, and rats in TM/PLGA group were locally implanted with TM/PLGA microspheres. Ten rats were selected randomly from each group for observing the survival time, and the other 10 rats were killed on POD 14 to measure proliferation activity and apoptosis of the gliomas. Head MRI examination was performed before the rats were killed. The median survival time of sham operation group, control group, blank PLGA microspheres group, oral TM group, and TM/PLGA group was 19.5, 20, 19, 27, and 46.5 days, respectively. MRI demonstrated that the tumor volume was reduced in oral TM group and interstitial TM/PLGA group. PCNA-positive cell staining showed that proliferation activity of tumor cells treated with interstitial TM/PLGA therapy significantly decreased when compared with that of tumor cells treated with oral TM therapy. The apoptosis of C6 cells in interstitial TM/PLGA group significantly increased when compared with that in oral TM group. Interstitial TM/PLGA was effective in treating intracranial C6 rat gliomas and could prove to be a potential chemotherapy agent for human malignant gliomas.
Zhang
Yu-Hui
YH
Department of Neurosurgery, Second Military Medical University Changhai Hospital, and Department of Pharmaceutics, Second Military Medical University School of Pharmacy, Shanghai, China.
Zhang
He
H
Liu
Jian-min
JM
Yue
Zhi-Jian
ZJ
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005910:Glioma / Q000188:drug therapy*; D020287:In Situ Nick-End Labeling; D019344:Lactic Acid / Q000008:administration & dosage*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D000077204:Temozolomide
D000970:Antineoplastic Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003606:Dacarbazine; D000077204:Temozolomide
Biomaterials. 1993 May;14(6):470-8
8507795
Cancer Chemother Pharmacol. 2003 Dec;52(6):459-64
13680160
Cancer. 1993 Apr 15;71(8):2585-97
8453582
Neuroepidemiology. 2009;32(1):21-9
18997474
J R Soc Interface. 2008 Sep 6;5(26):957-75
18477539
Ann Surg Oncol. 2008 Nov;15(11):3272-7
18712569
Ann Rheum Dis. 2005 Aug;64(8):1132-6
15695536
Expert Opin Drug Saf. 2009 Jul;8(4):493-9
19435405
Cancer Chemother Pharmacol. 2007 Oct;60(5):643-50
17256133
Crit Rev Ther Drug Carrier Syst. 1995;12(1):1-99
8521523
N Engl J Med. 2008 Jul 31;359(5):492-507
18669428
J Diabetes Sci Technol. 2008 Nov;2(6):1003-15
19885290
Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):999-1005
18258384
J Neurooncol. 2009 Sep;94(2):203-12
19337695
Clin Cancer Res. 1999 Feb;5(2):309-17
10037179
Cell Transplant. 2008;17(4):409-15
18522243
Int J Pharm. 2007 Feb 1;329(1-2):122-8
17000068
Cancer Treat Rev. 1997 Jan;23(1):35-61
9189180
J Clin Oncol. 1999 Sep;17(9):2762-71
10561351
Ann Surg Oncol. 2008 Oct;15(10):2887-93
18636295
Anticancer Res. 2009 Mar;29(3):911-7
19414327
Br J Cancer. 2000 Sep;83(5):588-93
10944597
Semin Oncol. 2003 Dec;30(6 Suppl 19):4-9
14765377
Cell Transplant. 1999 Jan-Feb;8(1):47-58
10338275