Tumor delivery of Photofrin® by PLL-g-PEG for photodynamic therapy

J Control Release. 2013 May 10;167(3):315-21. doi: 10.1016/j.jconrel.2013.02.016. Epub 2013 Feb 26.

Abstract

Photofrin® (porfimer sodium) is a photosensitive reagent used for photodynamic therapy (PDT) of tumors and dysplasias. Because only photo-irradiated sites are damaged, PDT is less invasive than systemic treatments. However, a photosensitive reaction is a major side effect of systemically delivered Photofrin. To enhance localization of Photofrin to tumors, we have formulated Photofrin with the tumor-localizing graft copolymer poly(ethylene glycol)-grafted poly(l-lysine), PLL-g-PEG. We demonstrate that Photofrin preferentially interacts with PLL-g-PEG through both ionic and hydrophobic interactions. The serum competitive study showed that the highly PEG-grafted PLL is better for preventing serum binding to the Photofrin/PLL-g-PEG complex. In tumor-bearing mice, formulation of Photofrin with PLL-g-PEG enhanced tumor localization of Photofrin as twice as Photofrin alone and concomitantly suppressed the photosensitivity reaction drastically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Blood Proteins / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dihematoporphyrin Ether / administration & dosage*
  • Dihematoporphyrin Ether / chemistry
  • Dihematoporphyrin Ether / pharmacokinetics
  • Light
  • Liver / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / metabolism*
  • Photochemotherapy
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacokinetics
  • Polyethylene Glycols / chemistry*
  • Polylysine / analogs & derivatives*
  • Polylysine / chemistry
  • Protein Binding

Substances

  • Antineoplastic Agents
  • Blood Proteins
  • Photosensitizing Agents
  • polylysine-graft-(poly(ethylene glycol))
  • Polylysine
  • Polyethylene Glycols
  • Dihematoporphyrin Ether