Paclitaxel tumor biodistribution and efficacy after intratumoral injection of a biodegradable extended release implant

Ariella Shikanov; Sergey Shikanov; Boris Vaisman; Jacob Golenser; Abraham J. Domb

doi:10.1016/j.ijpharm.2008.02.028

Paclitaxel tumor biodistribution and efficacy after intratumoral injection of a biodegradable extended release implant

Ariella Shikanov, Sergey Shikanov, Boris Vaisman, Jacob Golenser, Abraham J. Domb

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

Purpose: The aim of this study was to investigate the effectiveness of paclitaxel controlled release from intratumorally injected polymer. Methods: The effectiveness of paclitaxel-polymer formulation injected intratumorally was tested in mouse bladder tumor model. To determine paclitaxel biodistribution in tumor at predetermined time periods the tumor was excised, frozen and sectioned, and the paclitaxel concentrations were determined in the tumor tissue and in plasma by HPLC. Histopathological evaluation of the necrosis and inflammation was performed on tumor sections. Results: In the paclitaxel/polymer group mice were injected intratumorally with 0.2 ml of the 10% (w/w) paclitaxel formulation, the tumor disappeared completely 5 days after injection, and mice survived till the end of the study (50 days post-tumor cells inoculation). In biodistribution studies, the highest paclitaxel concentration in the tumor tissue was 40 μg/mg 1 day after the intratumoral injection and decreased gradually during 10 days to 5 μg/mg that is still high enough to induce cytotoxic effect, and the necrotic effect of paclitaxel on the tumors was confirmed by histopathology. Conclusions: Treatment with local injection of polymer-paclitaxel formulation inhibited the growth of solid tumors. Distribution studies of paclitaxel after intratumoral injection showed high and effective drug concentrations in tumor.

Original language	English
Pages (from-to)	114-120
Number of pages	7
Journal	International Journal of Pharmaceutics
Volume	358
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ijpharm.2008.02.028
State	Published - 24 Jun 2008
Externally published	Yes

Bibliographical note

Funding Information:
Filipe S. Oliveira gratefully acknowledges the financial support of FCT/MCTES (Portugal) through the PhD fellowship SFRH/BD/73761/2010 and Isabel M. Marrucho for a contract under FCT Investigator 2012 Program. The authors also acknowledge the Funda??o para a Ci?ncia e Tecnologia (FCT) for the financial support through the project PTDC/EQUFTT/1686/2012 and Research Unit GREEN-it "Bioresources for Sustainability" (UID/Multi/04551/2013). The NMR spectrometers are part of the National NMR Facility (RECI/BBB-BQB/0230/2012), also supported by FCT.

Funding

Filipe S. Oliveira gratefully acknowledges the financial support of FCT/MCTES (Portugal) through the PhD fellowship SFRH/BD/73761/2010 and Isabel M. Marrucho for a contract under FCT Investigator 2012 Program. The authors also acknowledge the Funda??o para a Ci?ncia e Tecnologia (FCT) for the financial support through the project PTDC/EQUFTT/1686/2012 and Research Unit GREEN-it "Bioresources for Sustainability" (UID/Multi/04551/2013). The NMR spectrometers are part of the National NMR Facility (RECI/BBB-BQB/0230/2012), also supported by FCT.

Funders	Funder number
Ci?ncia e Tecnologia	PTDC/EQUFTT/1686/2012, RECI/BBB-BQB/0230/2012, UID/Multi/04551/2013
FCT/MCTES	SFRH/BD/73761/2010
FundaÃ§Ã£o para a CiÃªncia e a Tecnologia

Keywords

Anti-tumor efficacy
Controlled release
Injectable biodegradable polymer
Paclitaxel
Poly(ester anhydride)
Tumor distribution

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10.1016/j.ijpharm.2008.02.028

Cite this

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title = "Paclitaxel tumor biodistribution and efficacy after intratumoral injection of a biodegradable extended release implant",

abstract = "Purpose: The aim of this study was to investigate the effectiveness of paclitaxel controlled release from intratumorally injected polymer. Methods: The effectiveness of paclitaxel-polymer formulation injected intratumorally was tested in mouse bladder tumor model. To determine paclitaxel biodistribution in tumor at predetermined time periods the tumor was excised, frozen and sectioned, and the paclitaxel concentrations were determined in the tumor tissue and in plasma by HPLC. Histopathological evaluation of the necrosis and inflammation was performed on tumor sections. Results: In the paclitaxel/polymer group mice were injected intratumorally with 0.2 ml of the 10% (w/w) paclitaxel formulation, the tumor disappeared completely 5 days after injection, and mice survived till the end of the study (50 days post-tumor cells inoculation). In biodistribution studies, the highest paclitaxel concentration in the tumor tissue was 40 μg/mg 1 day after the intratumoral injection and decreased gradually during 10 days to 5 μg/mg that is still high enough to induce cytotoxic effect, and the necrotic effect of paclitaxel on the tumors was confirmed by histopathology. Conclusions: Treatment with local injection of polymer-paclitaxel formulation inhibited the growth of solid tumors. Distribution studies of paclitaxel after intratumoral injection showed high and effective drug concentrations in tumor.",

keywords = "Anti-tumor efficacy, Controlled release, Injectable biodegradable polymer, Paclitaxel, Poly(ester anhydride), Tumor distribution",

author = "Ariella Shikanov and Sergey Shikanov and Boris Vaisman and Jacob Golenser and Domb, {Abraham J.}",

note = "Funding Information: Filipe S. Oliveira gratefully acknowledges the financial support of FCT/MCTES (Portugal) through the PhD fellowship SFRH/BD/73761/2010 and Isabel M. Marrucho for a contract under FCT Investigator 2012 Program. The authors also acknowledge the Funda??o para a Ci?ncia e Tecnologia (FCT) for the financial support through the project PTDC/EQUFTT/1686/2012 and Research Unit GREEN-it {"}Bioresources for Sustainability{"} (UID/Multi/04551/2013). The NMR spectrometers are part of the National NMR Facility (RECI/BBB-BQB/0230/2012), also supported by FCT.",

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AU - Shikanov, Sergey

AU - Vaisman, Boris

AU - Golenser, Jacob

AU - Domb, Abraham J.

N1 - Funding Information: Filipe S. Oliveira gratefully acknowledges the financial support of FCT/MCTES (Portugal) through the PhD fellowship SFRH/BD/73761/2010 and Isabel M. Marrucho for a contract under FCT Investigator 2012 Program. The authors also acknowledge the Funda??o para a Ci?ncia e Tecnologia (FCT) for the financial support through the project PTDC/EQUFTT/1686/2012 and Research Unit GREEN-it "Bioresources for Sustainability" (UID/Multi/04551/2013). The NMR spectrometers are part of the National NMR Facility (RECI/BBB-BQB/0230/2012), also supported by FCT.

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N2 - Purpose: The aim of this study was to investigate the effectiveness of paclitaxel controlled release from intratumorally injected polymer. Methods: The effectiveness of paclitaxel-polymer formulation injected intratumorally was tested in mouse bladder tumor model. To determine paclitaxel biodistribution in tumor at predetermined time periods the tumor was excised, frozen and sectioned, and the paclitaxel concentrations were determined in the tumor tissue and in plasma by HPLC. Histopathological evaluation of the necrosis and inflammation was performed on tumor sections. Results: In the paclitaxel/polymer group mice were injected intratumorally with 0.2 ml of the 10% (w/w) paclitaxel formulation, the tumor disappeared completely 5 days after injection, and mice survived till the end of the study (50 days post-tumor cells inoculation). In biodistribution studies, the highest paclitaxel concentration in the tumor tissue was 40 μg/mg 1 day after the intratumoral injection and decreased gradually during 10 days to 5 μg/mg that is still high enough to induce cytotoxic effect, and the necrotic effect of paclitaxel on the tumors was confirmed by histopathology. Conclusions: Treatment with local injection of polymer-paclitaxel formulation inhibited the growth of solid tumors. Distribution studies of paclitaxel after intratumoral injection showed high and effective drug concentrations in tumor.

AB - Purpose: The aim of this study was to investigate the effectiveness of paclitaxel controlled release from intratumorally injected polymer. Methods: The effectiveness of paclitaxel-polymer formulation injected intratumorally was tested in mouse bladder tumor model. To determine paclitaxel biodistribution in tumor at predetermined time periods the tumor was excised, frozen and sectioned, and the paclitaxel concentrations were determined in the tumor tissue and in plasma by HPLC. Histopathological evaluation of the necrosis and inflammation was performed on tumor sections. Results: In the paclitaxel/polymer group mice were injected intratumorally with 0.2 ml of the 10% (w/w) paclitaxel formulation, the tumor disappeared completely 5 days after injection, and mice survived till the end of the study (50 days post-tumor cells inoculation). In biodistribution studies, the highest paclitaxel concentration in the tumor tissue was 40 μg/mg 1 day after the intratumoral injection and decreased gradually during 10 days to 5 μg/mg that is still high enough to induce cytotoxic effect, and the necrotic effect of paclitaxel on the tumors was confirmed by histopathology. Conclusions: Treatment with local injection of polymer-paclitaxel formulation inhibited the growth of solid tumors. Distribution studies of paclitaxel after intratumoral injection showed high and effective drug concentrations in tumor.

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KW - Controlled release

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KW - Poly(ester anhydride)

KW - Tumor distribution

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ER -

Paclitaxel tumor biodistribution and efficacy after intratumoral injection of a biodegradable extended release implant

Abstract

Bibliographical note

Funding

Keywords

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