Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Zeeneh Elsaid*, Kevin M G Taylor, Sanyogitta Puri, Cath A. Eberlein, Khuloud Al-Jamal, Jie Bai, Rebecca Klippstein, Julie Tzu Wen Wang, Ben Forbes, Jasminder Chana, Satyanarayana Somavarapu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Many chemotherapeutics suffer from poor aqueous solubility and tissue selectivity. Distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) micelles are a promising formulation strategy for the delivery of hydrophobic anticancer drugs. However, storage and in vivo instability restrict their use. The aim of this study was to prepare mixed micelles, containing a novel polymer, lipoic acid-chitosan-poly(ethylene glycol) (LACPEG), and DSPE-PEG, to overcome these limitations and potentially increase cancer cell internalisation. Drug-loaded micelles were prepared with a model tyrosine kinase inhibitor and characterized for size, surface charge, stability, morphology, drug entrapment efficiency, cell viability (A549 and PC-9 cell lines), in vivo biodistribution, ex vivo tumor accumulation and cellular internalisation. Micelles of size 30–130 nm with entrapment efficiencies of 46–81% were prepared. LACPEG/DSPE-PEG mixed micelles showed greater interaction with the drug (condensing to half their size following entrapment), greater stability, and a safer profile in vitro compared to DSPE-PEG micelles. LACPEG/DSPE-PEG and DSPE-PEG micelles had similar entrapment efficiencies and in vivo tumor accumulation levels, but LACPEG/DSPE-PEG micelles showed higher tumor cell internalisation. Collectively, these findings suggest that LACPEG/DSPE-PEG mixed micelles provide a promising platform for tumor delivery of hydrophobic drugs.

Original languageEnglish
Pages (from-to)228-242
Number of pages15
JournalEUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume101
Early online date3 Feb 2017
DOIs
Publication statusPublished - 1 Apr 2017

Keywords

  • Biodistribution
  • Cancer
  • Chitosan
  • DSPE-PEG
  • Hydrophobic drug
  • Mixed micelles
  • Uptake

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