Development of a Gemcitabine-Polymer Conjugate with Prolonged Cytotoxicity against a Pancreatic Cancer Cell Line

Fanny Joubert, Liam Martin, Sebastien Perrier, George Pasparakis

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Gemcitabine (GEM) is a nucleoside analogue of deoxycytidine with limited therapeutic efficacy due to enzymatic hydrolysis by cytidine deaminase (CDA) resulting in compromised half-life in the bloodstream and poor pharmacokinetics. To overcome these limitations, we have developed a methacrylate-based GEM-monomer conjugate, which was polymerized by reversible addition-fragmentation chain transfer (RAFT) polymerization with high monomer conversion (∼90%) and low dispersity (<1.4). The resulting GEM-polymer conjugates were found to form well-defined sub-90 nm nanoparticles (NPs) in aqueous suspension. Subsequently, the GEM release was studied at different pH (∼7 and ∼5) with and without the presence of an enzyme, Cathepsin B. The GEM release profiles followed a pseudo zero-order rate and the GEM-polymer conjugate NPs were prone to acidic and enzymatic degradation, following a two-step hydrolysis mechanism. Furthermore, the NPs exhibited significant cytotoxicity in vitro against a model pancreatic cell line. Although, the half-maximal inhibitory concentration (IC50) of the GEM-monomer and-polymer conjugate NPs was higher than free GEM, the conjugates showed superiorly prolonged activity compared to the parent drug.

Original languageEnglish
Pages (from-to)535-540
Number of pages6
JournalACS Macro Letters
Volume6
Issue number5
DOIs
Publication statusPublished - 16 May 2017

Cite this

Joubert, Fanny ; Martin, Liam ; Perrier, Sebastien ; Pasparakis, George. / Development of a Gemcitabine-Polymer Conjugate with Prolonged Cytotoxicity against a Pancreatic Cancer Cell Line. In: ACS Macro Letters. 2017 ; Vol. 6, No. 5. pp. 535-540.
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Development of a Gemcitabine-Polymer Conjugate with Prolonged Cytotoxicity against a Pancreatic Cancer Cell Line. / Joubert, Fanny; Martin, Liam; Perrier, Sebastien; Pasparakis, George.

In: ACS Macro Letters, Vol. 6, No. 5, 16.05.2017, p. 535-540.

Research output: Contribution to journalArticleResearchpeer-review

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