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Effective light-triggered contents release from helper lipid-incorporated liposomes co-encapsulating gemcitabine and a water-soluble photosensitizer

Int J Pharm. 2018 Apr 5;540(1-2):50-56. doi: 10.1016/j.ijpharm.2018.01.040. Epub 2018 Feb 2.

Abstract

Triggered drug release is a promising strategy for delivering anticancer drugs to cancer cells and tissues. We found that liposomes co-encapsulating calcein (a water-soluble model drug and fluorescence marker) and talaporfin sodium (TPS, a water-soluble photosensitizer) released the drug upon irradiation with a near-infrared (NIR)-laser. The liposomes were composed of phospholipid (DSPC)/helper lipid (DOPE)/cholesterol/PEG-lipid (PEG2000-DSPE) at a molar ratio of 85/10/5/5 and released a large amount of drug (70%<, within 10 min) upon irradiation, but no drug in the absence of NIR-laser irradiation and/or TPS. NIR-laser-triggered drug release was facilitated by the incorporation of DOPE into the liposomes, and the amount of DOPE incorporated affected drug leakage in the absence of NIR-laser-irradiation at 37 °C (body temperature). Drug leakage was tuned by incorporating cholesterol into the liposomes. NIR-laser-triggered drug release from the liposomes was confirmed using the anticancer drug gemcitabine. NIR-laser treatment of liposomes co-encapsulating gemcitabine and TPS provided the maximum cytotoxic effect towards EMT6/P cells. These results suggest that these novel light sensitive liposomes may be useful for drug delivery to cancer cells.

Keywords: Cancer; Gemcitabine; Liposome; Near-infrared (NIR)-laser; Talaporfin sodium; Triggered release.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / chemistry*
  • Antimetabolites, Antineoplastic / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Delayed-Action Preparations
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / chemistry
  • Deoxycytidine / pharmacology
  • Drug Compounding
  • Drug Liberation
  • Female
  • Gemcitabine
  • Infrared Rays*
  • Kinetics
  • Lipids / chemistry
  • Liposomes
  • Mice
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / pharmacology
  • Porphyrins / chemistry*
  • Porphyrins / pharmacology
  • Solubility
  • Technology, Pharmaceutical / methods
  • Water / chemistry*

Substances

  • Antimetabolites, Antineoplastic
  • Delayed-Action Preparations
  • Lipids
  • Liposomes
  • Photosensitizing Agents
  • Porphyrins
  • Water
  • Deoxycytidine
  • Talaporfin
  • Gemcitabine