PH-dependent complexation of hydroxypropyl-beta-cyclodextrin with chlorin e6: Effect on solubility and aggregation in relation to photodynamic efficacy

Shubhajit Paul, Paul Wan Sia Heng, Lai Wah Chan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Objectives The activity of chlorin e6 (Ce6) in photodynamic therapy of cancers is significantly reduced by its propensity to form aggregates. It was postulated that disaggregation of Ce6 could be achieved with the use of hydroxypropyl-beta-cyclodextrin (HP-β-CD) through solubility enhancement. Methods An initial phase solubility study of Ce6 was conducted with various concentrations of HP-β-CD at three different pH conditions, i.e. pH 3, pH 5 and pH 7. Solubility-induced disaggregation of Ce6 was illustrated by fluorescence spectroscopy and singlet oxygen generation studies. Interaction between Ce6 and HP-β-CD was further demonstrated by solid-state characterization techniques. Inclusion complex formulations were tested for improved efficacy on squamous cancer cell lines. Key findings Increase in Ce6 solubility was observed, especially at pH 7, indicating the formation of inclusion complex between Ce6 and HP-β-CD. This resulted in disaggregation of Ce6 aggregates illustrated by fluorescence spectroscopy. The mode of binding was predominated by H-bonding supported by temperature-dependent binding studies and molecular simulation work. The inclusion complex demonstrated improved photodynamic efficacy through enhanced singlet oxygen generation and phototoxicity on human oral squamous carcinoma cells. Conclusions pH-dependent complexation between Ce6- and HP-β-CD-induced disaggregation of Ce6 aggregates and the resultant formulations facilitated improved PDT efficacy on tested cancer cell lines.

Original languageEnglish (US)
Pages (from-to)439-449
Number of pages11
JournalJournal of Pharmacy and Pharmacology
Volume68
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • drug delivery to specific tissues
  • pharmaceutical analysis
  • pharmaceutics and drug delivery, drug characterisation studies

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