Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation.
In order to examine the efficacy of paclitaxel (Taxol, Bristol-Myers Squibb) after administration locally at the tumor site, we have developed a thermo-reversible gelling formulation in poloxamer 407 (Pluronic F-127) solution. Paclitaxel was incorporated in poloxamer 407 [20% (w/w)] at 0.5- and 1.0-mg/mL concentrations. The in vitro release studies were carried out in phosphate-buffered saline (pH 7.4) at 37 degrees C. Control and paclitaxel-poloxamer 407 formulations were administered intratumorally at a dose of 20 mg/kg in B16F1 melanoma-bearing mice. The change in tumor volume as a function of time and the survival of treated animals were used as measures of efficacy. Poloxamer 407 solution undergoes a reversible sol-gel transition when the temperature is raised to above 21 degrees C. In vitro paclitaxel release from poloxamer 407 gels was very slow (only 6.1% after 6 hr) probably due to the poor aqueous solubility of the drug. Significant enhancement in the anti-tumor efficacy was noted following intratumoral administration of paclitaxel-poloxamer 407 formulation. The initial tumor growth rate was delayed by 67% and the tumor volume doubling time was increased by 72% relative to saline control. In addition, more than 91% of the tumor-bearing animals that received paclitaxel in poloxamer 407 gel survived on day 15 post-administration as compared to 58% in the control group. The results of this study show significant benefit of paclitaxel for solid tumor when administered locally in an in situ gelling poloxamer 407 formulation.
Amiji
Mansoor M
MM
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, USA. m.amiji@neu.edu
Lai
Phung-Kim
PK
Shenoy
Dinesh B
DB
Rao
Mahadev
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D005782:Gels; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D020442:Poloxamer / Q000008:administration & dosage*; D012995:Solubility
D000972:Antineoplastic Agents, Phytogenic; D005782:Gels; D020442:Poloxamer; D017239:Paclitaxel