Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation

M.M. Amiji, P.-K. Lai, D.B. Shenoy, M. Rao

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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°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°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.
Original languageEnglish
Pages (from-to)195-202
Number of pages8
JournalPharmaceutical Development and Technology
Volume7
Issue number2
DOIs
Publication statusPublished - 2002

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Poloxamer
Paclitaxel
Gels
Neoplasms
Tumor Burden
Transition Temperature
Polymethyl Methacrylate
Solubility
Melanoma
Phosphates
Control Groups

Cite this

@article{e525452d9d1945798ea3a69fbb66b0dc,
title = "Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation",
abstract = "In order to examine the efficacy of paclitaxel (Taxol{\circledR}, Bristol-Myers Squibb) after administration locally at the tumor site, we have developed a thermo-reversible gelling formulation in poloxamer 407 (Pluronic{\circledR} 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°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°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.",
author = "M.M. Amiji and P.-K. Lai and D.B. Shenoy and M. Rao",
note = "Cited By :42 Export Date: 10 November 2017 CODEN: PDTEF Correspondence Address: Amiji, M.M.; Dept. of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, United States; email: m.amiji@neu.edu Chemicals/CAS: Antineoplastic Agents, Phytogenic; Gels; Paclitaxel, 33069-62-4; Poloxamer, 106392-12-5 Manufacturers: Bristol Myers Squibb, United States References: Jain, R.K., Delivery of molecular and cellular medicine to solid tumors (1997) Adv. Drug Delivery Rev., 26, pp. 71-90; Fung, L.K., Saltzman, W.M., Polymeric implants for cancer chemotherapy (1997) Adv. Drug Delivery Rev., 26, pp. 209-230; Dhanikula, A.B., Panchagnula, R., Localized paclitaxel delivery (1999) Int. J. Pharm., 183, pp. 85-100; Panchagnula, R., Pharmaceutical aspects of paclitaxel (1998) Int. J. Pharm., 172, pp. 1-15; Spencer, C.M., Faulds, D., Paclitaxel: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer (1994) Drugs, 48, pp. 794-847; Okataba, A.M., Arsenault, A.L., Hunter, W.L., Taxol: A potent inhibitor of normal and tumor-induced angiogenesis (1995) Proc. Am. Assoc. Cancer Res., 36, p. 454; Millenbaugh, N.J., Gan, Y., Au, J.L.-S., Cytostatic and apoptotic effects of paclitaxel in human ovarian tumors (1998) Pharm. Res., 15, pp. 122-127; Mote, P.A., Davey, M.W., Davey, R.A., Oliver, L., Paclitaxel sensitizes multidrug resistant cells to radiation (1996) Anticancer Drugs, 7, pp. 182-188; Nicholson, K.M., Bibby, M.C., Phillips, R.M., Influence of drug exposure parameters on the activity of paclitaxel in multicellular spheroids (1997) Eur. J. Cancer, 33, pp. 1291-1298; Harper, E., Dang, W., Lapidus, R.G., Garver R.I., Jr., Enhanced efficacy of a novel controlled release paclitaxel formulation (PACLIMER delivery system) for local-regional therapy of lung cancer tumor nodules in mice (1999) Clin. Cancer Res., 5, pp. 4242-4248; Winternitz, C.I., Jackson, J.K., Okataba, A.M., Burt, H.M., Development of polymeric surgical paste formulation for taxol (1996) Pharm. Res., 13, pp. 368-375; Park, E.-S., Maniar, M., Shah, J.C., Biodegradable polyanhydride devices of cefazolin sodium, bupivacaine, and taxol for local drug delivery: Preparation and kinetics and mechanism of in vitro release (1998) J. Control. Release, 52, pp. 179-189; Lundsted, L.G., Schmolka, I.R., The synthesis and properties of block copolymer surfactants (1976) Block and Graft Copolymerization, pp. 1-111. , Ceresa, R.J., Ed.; John Wiley and Sons: New York, NY; Paavola, A., Yliruusi, J., Kojimoto, Y., Kalso, E., Wahlstrom, T., Rosenberg, P., Controlled release of lidocaine from injectable gels and efficacy in rat sciatic nerve block (1995) Pharm. Res., 12, pp. 1997-2002; Katakam, M., Ravis, W.R., Banga, A.K., Controlled release of human growth hormone in rats following parenteral administration of poloxamer gels (1997) J. Control. Release, 49, pp. 21-26; Pandit, N.K., McIntyre, H.J., Cosolvent effects on the gel formation and gel melting transitions of pluronic{\circledR} F127 gels (1997) Pharm. Dev. Technol., 2, pp. 181-184; Lai, P.K., Nguyen, T., Amiji, M., Novel thermogelling paclitaxel formulation for localized delivery (1999) Trans. Soc. Biomater., 22, p. 321; Rao, M., Kamath, R., Rao, M.N.A., Protective effect of selenomethionine against cisplatin-induced nephrotoxicity in C57BL/6J mice bearing B16F1 melanoma without reducing antitumor activity (1998) Pharm. Pharmacol. Commun., 4, pp. 549-552; Sharma, D., Chelvi, T.P., Kaur, J., Chakravorty, K., De, T.K., Maitra, A., Ralhan, R., Novel Taxol{\circledR} formulations: Polyvinylpyrrolidone nanoparticle-encapsulated taxol{\circledR} for drug delivery in cancer therapy (1996) Oncol. Res., 8, pp. 281-286; Vadnere, M., Amidon, G., Lindenbaum, S., Haslam, J.L., Thermodynamic studies on the gel-sol transition of some pluronic polyols (1984) Int. J. Pharm., 22, pp. 207-218",
year = "2002",
doi = "10.1081/PDT-120003487",
language = "English",
volume = "7",
pages = "195--202",
journal = "Pharmaceutical Development and Technology",
issn = "1083-7450",
publisher = "Informa Healthcare",
number = "2",

}

Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation. / Amiji, M.M.; Lai, P.-K.; Shenoy, D.B.; Rao, M.

In: Pharmaceutical Development and Technology, Vol. 7, No. 2, 2002, p. 195-202.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation

AU - Amiji, M.M.

AU - Lai, P.-K.

AU - Shenoy, D.B.

AU - Rao, M.

N1 - Cited By :42 Export Date: 10 November 2017 CODEN: PDTEF Correspondence Address: Amiji, M.M.; Dept. of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, United States; email: m.amiji@neu.edu Chemicals/CAS: Antineoplastic Agents, Phytogenic; Gels; Paclitaxel, 33069-62-4; Poloxamer, 106392-12-5 Manufacturers: Bristol Myers Squibb, United States References: Jain, R.K., Delivery of molecular and cellular medicine to solid tumors (1997) Adv. Drug Delivery Rev., 26, pp. 71-90; Fung, L.K., Saltzman, W.M., Polymeric implants for cancer chemotherapy (1997) Adv. Drug Delivery Rev., 26, pp. 209-230; Dhanikula, A.B., Panchagnula, R., Localized paclitaxel delivery (1999) Int. J. Pharm., 183, pp. 85-100; Panchagnula, R., Pharmaceutical aspects of paclitaxel (1998) Int. J. Pharm., 172, pp. 1-15; Spencer, C.M., Faulds, D., Paclitaxel: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer (1994) Drugs, 48, pp. 794-847; Okataba, A.M., Arsenault, A.L., Hunter, W.L., Taxol: A potent inhibitor of normal and tumor-induced angiogenesis (1995) Proc. Am. Assoc. Cancer Res., 36, p. 454; Millenbaugh, N.J., Gan, Y., Au, J.L.-S., Cytostatic and apoptotic effects of paclitaxel in human ovarian tumors (1998) Pharm. Res., 15, pp. 122-127; Mote, P.A., Davey, M.W., Davey, R.A., Oliver, L., Paclitaxel sensitizes multidrug resistant cells to radiation (1996) Anticancer Drugs, 7, pp. 182-188; Nicholson, K.M., Bibby, M.C., Phillips, R.M., Influence of drug exposure parameters on the activity of paclitaxel in multicellular spheroids (1997) Eur. J. Cancer, 33, pp. 1291-1298; Harper, E., Dang, W., Lapidus, R.G., Garver R.I., Jr., Enhanced efficacy of a novel controlled release paclitaxel formulation (PACLIMER delivery system) for local-regional therapy of lung cancer tumor nodules in mice (1999) Clin. Cancer Res., 5, pp. 4242-4248; Winternitz, C.I., Jackson, J.K., Okataba, A.M., Burt, H.M., Development of polymeric surgical paste formulation for taxol (1996) Pharm. Res., 13, pp. 368-375; Park, E.-S., Maniar, M., Shah, J.C., Biodegradable polyanhydride devices of cefazolin sodium, bupivacaine, and taxol for local drug delivery: Preparation and kinetics and mechanism of in vitro release (1998) J. Control. Release, 52, pp. 179-189; Lundsted, L.G., Schmolka, I.R., The synthesis and properties of block copolymer surfactants (1976) Block and Graft Copolymerization, pp. 1-111. , Ceresa, R.J., Ed.; John Wiley and Sons: New York, NY; Paavola, A., Yliruusi, J., Kojimoto, Y., Kalso, E., Wahlstrom, T., Rosenberg, P., Controlled release of lidocaine from injectable gels and efficacy in rat sciatic nerve block (1995) Pharm. Res., 12, pp. 1997-2002; Katakam, M., Ravis, W.R., Banga, A.K., Controlled release of human growth hormone in rats following parenteral administration of poloxamer gels (1997) J. Control. Release, 49, pp. 21-26; Pandit, N.K., McIntyre, H.J., Cosolvent effects on the gel formation and gel melting transitions of pluronic® F127 gels (1997) Pharm. Dev. Technol., 2, pp. 181-184; Lai, P.K., Nguyen, T., Amiji, M., Novel thermogelling paclitaxel formulation for localized delivery (1999) Trans. Soc. Biomater., 22, p. 321; Rao, M., Kamath, R., Rao, M.N.A., Protective effect of selenomethionine against cisplatin-induced nephrotoxicity in C57BL/6J mice bearing B16F1 melanoma without reducing antitumor activity (1998) Pharm. Pharmacol. Commun., 4, pp. 549-552; Sharma, D., Chelvi, T.P., Kaur, J., Chakravorty, K., De, T.K., Maitra, A., Ralhan, R., Novel Taxol® formulations: Polyvinylpyrrolidone nanoparticle-encapsulated taxol® for drug delivery in cancer therapy (1996) Oncol. Res., 8, pp. 281-286; Vadnere, M., Amidon, G., Lindenbaum, S., Haslam, J.L., Thermodynamic studies on the gel-sol transition of some pluronic polyols (1984) Int. J. Pharm., 22, pp. 207-218

PY - 2002

Y1 - 2002

N2 - 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°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°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.

AB - 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°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°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.

U2 - 10.1081/PDT-120003487

DO - 10.1081/PDT-120003487

M3 - Article

VL - 7

SP - 195

EP - 202

JO - Pharmaceutical Development and Technology

JF - Pharmaceutical Development and Technology

SN - 1083-7450

IS - 2

ER -