Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors

Joshua Williams; Rachael Lansdown; Robert Sweitzer; Marek Romanowski; Rachel LaBell; Rajan Ramaswami; Evan Unger

doi:10.1016/S0168-3659(03)00241-4

Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors

Joshua Williams
, Rachael Lansdown
, Robert Sweitzer
, Marek Romanowski
, Rachel LaBell
, Rajan Ramaswami
, Evan Unger

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

143 Scopus citations

Abstract

Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar® in a mouse xenograft tumor model.

Original language	English (US)
Pages (from-to)	167-172
Number of pages	6
Journal	Journal of Controlled Release
Volume	91
Issue number	1-2
DOIs	https://doi.org/10.1016/S0168-3659(03)00241-4
State	Published - Aug 28 2003

Keywords

Efficacy
Formulation
Lactone stability
Nanoparticle
SN-38

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.1016/S0168-3659(03)00241-4

Cite this

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abstract = "Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar{\textregistered} in a mouse xenograft tumor model.",

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AU - Williams, Joshua

AU - Lansdown, Rachael

AU - Sweitzer, Robert

AU - Romanowski, Marek

AU - LaBell, Rachel

AU - Ramaswami, Rajan

AU - Unger, Evan

PY - 2003/8/28

Y1 - 2003/8/28

N2 - Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar® in a mouse xenograft tumor model.

AB - Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar® in a mouse xenograft tumor model.

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KW - Formulation

KW - Lactone stability

KW - Nanoparticle

KW - SN-38

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JO - Journal of Controlled Release

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ER -

Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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