[The inhibitory effect of paclitaxel nanoparticles on ovarian cancer xenografts and lymphatic targeting].
OBJECTIVE
To develop a polymeric drug delivery system for paclitaxel and determine whether paclitaxel can inhibit the growth of ovarian carcinoma xenografts in F344 rats by intraperitoneal administration.


METHODS
Paclitaxel loading nanoparticles (PLA) were synthesized by ultrasonic emulsification; rat ovarian carcinoma cells were injected into the peritoneal cavity of F344 rats. The antitumor effect of paclitaxel nanoparticles in vivo has been evaluated by measuring tumor weight and ascite volume. At the end of the procedure the rats were killed, tumors were excised and processed for PCNA staining, tissue terminal deoxynucleotide transferase-mediated dUTP nick and labeling (TUNEL) assay. Paclitaxel concentration in plasma, pelvic lymph nodes, liver, heart were determined by high-performance liquid chromatography (HPLC).


RESULTS
In the implanted carcinoma cells, paclitaxel nanoparticles significantly reduced tumor weight [(4.55 +/- 0.11) g vs (10.13 +/- 0.52) g]and ascites volume [(3.55 +/- 0.50) mL vs (30.45 +/- 1.55) mL], and induced apoptosis of tumor cells [(105 +/- 15) vs (55 +/- 10)]. The paclitaxel concentration of pelvic lymph nodes in PLA treated animals was significantly higher than that of free PTX treated animals 48 h after intraperitoneal administration [(0.75 +/- 0.05) microg/g vs (0.188 +/- 0.045) microg/g].


CONCLUSIONS
The intraperitoneal administration of paclitaxel nanoparticles can significantly inhibit the progression of ovarian carcinoma in peritoneal cavity of female F344 rats. The paclitaxel nanoparticle is safe and lymphatic targeting.
Lu
Hong-xia
HX
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
Xu
Cong-jian
CJ
Li
Bin
B
Kang
Yu
Y
Huang
Qian
Q
Li
Li-min
LM
Chen
Qing-hua
QH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D007150:Immunohistochemistry; 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; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
D000972:Antineoplastic Agents, Phytogenic; D018809:Proliferating Cell Nuclear Antigen; D017239:Paclitaxel