Physicochemical stability of bioadhesive thermoresponsive platforms for methylene blue and hypericin delivery in photodynamic therapy

Pharm Dev Technol. 2020 Apr;25(4):482-491. doi: 10.1080/10837450.2019.1711394. Epub 2020 Jan 8.

Abstract

Hypericin (Hyp), a natural hydrophobic and photoactive pigment, and methylene blue (MB), a hydrophilic cationic dye, are utilized as photosensitizer (PS) for photodynamic therapy of cancer. Bioadhesive and thermoresponsive polymeric systems can improve the drug availability by increasing the contact time between the system and the mucosa and also controlling the drug release. In this work, an accelerated physicochemical stability study of binary polymeric systems composed of poloxamer 407 (Polox) and Carbopol 934 P (Carb) for MB or Hyp release was performed. Formulations were prepared containing Polox (20%, w/w), Carb (0.15%, w/w) and MB (0.25%, w/w) or Hyp (0.01%, W/W) and submitted to different stress conditions (5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C with relative humidity of 75 ± 5%) during 180 days. The samples were analyzed as macroscopic characteristics, photosensitizer content and mechanical properties by texture profile analysis. Both systems displayed decrease of photosensitizer content less than 5% during 180 days. MB-system showed an undefined reaction model, while Hyp-system displayed PS decay following a pseudo first-order reaction. Systems also displayed stable mechanical characteristics. The pharmaceutical analyses showed the good physicochemical stability of the bioadhesive platform for delivery Hyp and MB in photodynamic therapy.

Keywords: Photosensitizer content; accelerated stability study; hypericin; mechanical properties; methylene blue; polymeric system.

MeSH terms

  • Acrylates / chemistry
  • Adhesives / chemistry
  • Anthracenes
  • Delayed-Action Preparations / chemistry*
  • Drug Delivery Systems
  • Drug Liberation
  • Drug Stability
  • Humans
  • Methylene Blue / administration & dosage*
  • Methylene Blue / chemistry
  • Neoplasms / drug therapy
  • Perylene / administration & dosage
  • Perylene / analogs & derivatives*
  • Perylene / chemistry
  • Photochemotherapy
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / chemistry
  • Poloxamer / chemistry
  • Temperature

Substances

  • Acrylates
  • Adhesives
  • Anthracenes
  • Delayed-Action Preparations
  • Photosensitizing Agents
  • Poloxamer
  • Perylene
  • hypericin
  • carbopol 934P
  • Methylene Blue