Porphyrin-phospholipid liposomes with tunable leakiness

J Control Release. 2015 Dec 28;220(Pt A):484-494. doi: 10.1016/j.jconrel.2015.11.011. Epub 2015 Nov 11.

Abstract

Drug bioavailability is a key consideration for drug delivery systems. When loaded with doxorubicin, liposomes containing 5 molar % porphyrin-phospholipid (HPPH liposomes) exhibited in vitro and in vivo serum stability that could be fine-tuned by varying the drug-to-lipid ratio. A higher drug loading ratio destabilized the liposomes, in contrast to standard liposomes which displayed an opposite and less pronounced trend. Following systemic administration of HPPH liposomes, near infrared laser irradiation induced vascular photodynamic damage, resulting in enhanced liposomal doxorubicin accumulation in tumors. In laser-irradiated tumors, the use of leaky HPPH liposomes resulted in improved doxorubicin bioavailability compared to stable standard liposomes. Using this approach, a single photo-treatment with 10mg/kg doxorubicin rapidly eradicated tumors in athymic nude mice bearing KB or MIA Paca-2 xenografts.

Keywords: Cancer; Doxorubicin; Liposomes; Photodynamic therapy; Porphyrin; Vasculature.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Biological Availability
  • Chlorophyll / administration & dosage
  • Chlorophyll / analogs & derivatives*
  • Chlorophyll / chemistry
  • Chlorophyll / pharmacokinetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Drug Compounding
  • Drug Stability
  • Female
  • HeLa Cells
  • Humans
  • Injections, Intravenous
  • Liposomes
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phospholipids / chemistry*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacokinetics
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics
  • Solubility
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Liposomes
  • Phospholipids
  • Photosensitizing Agents
  • liposomal doxorubicin
  • Chlorophyll
  • 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a
  • Polyethylene Glycols
  • Doxorubicin