Paclitaxel nanoparticle inhibits growth of ovarian cancer xenografts and enhances lymphatic targeting.
OBJECTIVE
Ovarian cancer has the highest mortality of all the gynecologic cancers. The antitumor agent paclitaxel has been proved to be efficient in the treatment of ovarian cancer. Our study is to develop a polymeric drug delivery system for paclitaxel and determine whether paclitaxel nanoparticle can inhibit growth of ovarian carcinoma xenografts in Fisher344 (F344) rats by intraperitoneal administration. The mechanism of paclitaxel nanoparticles in rats bearing ovarian cancer has been investigated in this study.


METHODS
Synthesize paclitaxel loading nanoparticle (PLA) by ultrasonic emulsification; MTT analysis identified cytotoxic activity of paclitaxel nanoparticle in vitro; rat ovarian carcinoma cells were injected into the peritoneal cavity of F344 rats. The antitumor effect of paclitaxel nanoparticle in vivo has been evaluated by measuring tumor weight and ascite volume. At the end of the procedure rats were sacrificed; tumors were excised and processed for PCNA staining, tissue terminal deoxynucleotide transferase-mediated dUTP nick and labeling assay and RT-PCR to evaluate the proliferative and apoptotic changes and cancer transfer-related gene expression induced by PLA. Paclitaxel concentration in plasma, pelvic lymph nodes, liver, and heart were determined by high-performance liquid chromatography.


RESULTS
Paclitaxel nanoparticle and PTX (Cremophor) showed equivalent cytotoxic activity in vitro. In rats implanted carcinoma cells, paclitaxel nanoparticles significantly reduced tumor weight and ascites volume, and induced apoptosis of tumor cells. PLA also inhibited cell proliferation and matrix metalloproteinase 9 mRNA expression. The paclitaxel concentration of pelvic lymph nodes in PLA treated animals was 20-fold higher than that of free PTX treated animals at 48 h after intraperitoneal administration.


CONCLUSIONS
The intraperitoneal administration of paclitaxel nanoparticle can significantly inhibit the progression of ovarian carcinoma in peritoneal cavity of female F344 rat. The paclitaxel nanoparticle is safe and lymphatic targeting.
Lu
Hongxia
H
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Li
Bin
B
Kang
Yu
Y
Jiang
Wei
W
Huang
Qian
Q
Chen
Qinghua
Q
Li
Limin
L
Xu
Congjian
C
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001201:Ascites / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042601:Lymphatic Vessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D053758:Nanoparticles / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D017239:Paclitaxel