Nanoparticle albumin-bound mTHPC for photodynamic therapy: Preparation and comprehensive characterization of a promising drug delivery system

Int J Pharm. 2020 May 30:582:119347. doi: 10.1016/j.ijpharm.2020.119347. Epub 2020 Apr 18.

Abstract

Nanoparticle albumin-bound (nab)-technology is an industrial applicable manufacturing method for the preparation of albumin-based drug carriers of poorly water-soluble drugs. In the present study the advantages of nanotechnology, albumin as an endogenous protein with the capability of high tumor enrichment and the selective light activation of the photosensitizer Temoporfin (mTHPC) were combined to a new delivery system for oncological use. The herewith provided well-established photodynamic therapy may enable a beneficial alternative for the treatment of solid tumors. In the present study a reproducible method for the preparation of stable mTHPC-albumin nanoparticles via nab-technology was established. The nanoparticles were physicochemically characterized with regard to particle size and size distribution and the impact of this preparation method on nanoparticle as well as mTHPC stability was investigated. Nanoparticles with improved colloidal stability over a broad pH range and in the presence of physiological NaCl concentrations were achieved in high yield. Due to high pressure homogenization a certain oxidative decay of mTHPC was observed. Cell culture experiments revealed an effective cellular uptake of mTHPC in a cholangiocarcinoma cell line (TFK-1). After light-activation high cytotoxicity was shown for photosensitizer loaded nanoparticles enabling the application of the proposed formulation in photodynamic therapy.

Keywords: Albumin; Cancer therapy; Nanoparticle albumin bound (nab)-technology; Nanoparticles; Photodynamic therapy; TFK-1 cells; mTHPC.

MeSH terms

  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology
  • Drug Carriers*
  • Drug Compounding
  • Drug Liberation
  • Drug Stability
  • Humans
  • Mesoporphyrins / chemistry
  • Mesoporphyrins / metabolism
  • Mesoporphyrins / pharmacology*
  • Nanoparticles*
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / metabolism
  • Photosensitizing Agents / pharmacology*
  • Serum Albumin, Bovine / chemistry*
  • Solubility

Substances

  • Drug Carriers
  • Mesoporphyrins
  • Photosensitizing Agents
  • Serum Albumin, Bovine
  • temoporfin