Synthesis and characterization of TPGS– gemcitabine prodrug micelles for pancreatic cancer therapy

Vaibhav Khare, Wejdan Al Shakarchi, Prem. N. Gupta, Anthony D. M. Curtis, Clare Hoskins

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The therapeutic potential of a nucleoside analog, gemcitabine, is severely compromised due to its rapid clearance from systemic circulation by enzymatic degradation into an inactive metabolite. In the present investigation, micelles based on polymer–drug conjugate were developed for gemcitabine and investigated for their potential to improve cancer chemotherapy. The tocopherol poly(ethylene glycol) succinate 1000 (TPGS)–gemcitabine prodrug was synthesized via an amide linkage and characterised by analytical methods, including FT-IR, 1H NMR, and MALDI-TOF. The micellar formulation of TPGS–gemcitabine prodrug was developed by a self-assembly technique and evaluated for various physicochemical parameters including particle size, polydispersity, morphology, critical micelle concentration and release profile. It was observed that gemcitabine present in TPGS–gemcitabine micelles was resistant to deamination by crude cytidine deaminase. The improved cytotoxicity of the micellar formulation was observed using TPGS–gemcitabine micelles against pancreatic cancer cells. Further, it was found that, unlike native gemcitabine, nucleoside transporters were not required for TPGS–Gem micelles to demonstrate their anticancer potential. These findings revealed that TPGS–gemcitabine micelles may serve as a promising platform for gemcitabine in order to improve its anticancer efficacy.
LanguageEnglish
Pages60126-60137
Number of pages12
JournalRSC Advances
Volume6
Issue number65
DOIs
Publication statusPublished - 15 Jun 2016

Fingerprint

gemcitabine
Tocopherols
Prodrugs
Micelles
Succinic Acid
Polyethylene glycols
Gems
Chemotherapy
Critical micelle concentration
Polydispersity
Cytotoxicity
Metabolites
Amides
Self assembly
Nucleoside Transport Proteins
Cytidine Deaminase
Particle size
Cells
Nuclear magnetic resonance
Degradation

Keywords

  • pancreatic cancer
  • nucleoside analog
  • gemcitabine
  • micelles
  • chemotherapy

Cite this

Khare, Vaibhav ; Al Shakarchi, Wejdan ; Gupta, Prem. N. ; Curtis, Anthony D. M. ; Hoskins, Clare. / Synthesis and characterization of TPGS– gemcitabine prodrug micelles for pancreatic cancer therapy. In: RSC Advances. 2016 ; Vol. 6, No. 65. pp. 60126-60137.
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Synthesis and characterization of TPGS– gemcitabine prodrug micelles for pancreatic cancer therapy. / Khare, Vaibhav; Al Shakarchi, Wejdan; Gupta, Prem. N.; Curtis, Anthony D. M.; Hoskins, Clare.

In: RSC Advances, Vol. 6, No. 65, 15.06.2016, p. 60126-60137.

Research output: Contribution to journalArticle

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