Preclinical efficacy studies of a novel nanoparticle-based formulation of paclitaxel that out-performs Abraxane.
OBJECTIVE
Poly-(gamma-L-glutamylglutamine)-paclitaxel (PGG-PTX) is a novel polymer-based formulation of paclitaxel (PTX) in which the PTX is linked to the polymer via ester bonds. PGG-PTX is of interest because it spontaneously forms very small nanoparticles in plasma. In mouse models, PGG-PTX increased tumor exposure to PTX by 7.7-fold relative to that produced by PTX formulated in Cremophor. In this study, the efficacy of PGG-PTX was compared to that of Abraxane, an established nanoparticular formulation of PTX, in three different tumor models.


METHODS
Efficacy was quantified by delay in tumor growth of NCI H460 human lung cancer, 2008 human ovarian cancer and B16 melanoma xenografts growing in athymic mice following administration of equitoxic doses of PGG-PTX and Abraxane administered on either a single dose or every 7 day schedule. Toxicity was assessed by change in total body weight.


RESULTS
The efficacy and toxicity of PGG-PTX was shown to increase with dose in the H460 model. PGG-PTX was approximately 1.5-fold less potent than Abraxane. PGG-PTX produced statistically significantly greater inhibition of tumor growth than Abraxane in all three tumor models when mice were given single equitoxic doses of drug. When given every 7 days for 3 doses, PGG-PTX produced greater inhibition of tumor growth while generating much less weight loss in mice bearing H460 tumors.


CONCLUSIONS
PGG-PTX has activity that is superior to that of Abraxane in multiple tumor models. PGG-PTX has the potential to out-perform Abraxane in enhancing the delivery of PTX tumors while at the same time further reducing the toxicity of both single dose and weekly treatment regimens.
Feng
Zhongling
Z
Biogroup, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058, USA.
Zhao
Gang
G
Yu
Lei
L
Gough
David
D
Howell
Stephen B
SB
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D011506:Proteins / Q000737:chemistry / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; D011506:Proteins; C548171:poly(gamma-glutamylglutamine)paclitaxel; D017239:Paclitaxel
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