Poloxamers-based nanomicelles as delivery vehicles of hypericin for hepatic photodynamic therapy

Abstract

Polymeric micelles in oxyalkylic blocks have been investigated as carriers of hydrophobic photosensitizers for intravenous administration in photodynamic therapy. This study evaluated the uptake of hypericin carried by polymeric micelles formed with Pluronics® P123, F127 and P84 and their photoinduced actions on gluconeogenesis in perfused livers of mice. Uptake and photoinduced action of F127-carried hypericin were also evaluated against cultured human hepatoblastoma HepG2 cells. Respiratory activity was assessed in isolated hepatic mitochondria. Hypericin is also investigated as a promising photosensitizer and it was herein photoinduced with red light. This procedure should activate this agent to a lower extension and prevent damage against healthy tissues. Hypericin carried by P123, P84 and F127 micelles was substantially taken up by perfused livers of healthy mice. However, P123 and P84 inhibited hepatic gluconeogenesis by impairing the aerobic energy supply of the cell, effects probably associated with their more hydrophobic character. Hypericin carried by F127, a more hydrophilic micelle, did not inhibit gluconeogenesis and did not modify the mitochondrial respiration at concentrations lower than 2 μM in the dark or when photoinduced with red light. What is more, F127-carried hypericin was substantially taken up by HepG2 cells and, when photoinduced with red light, considerably decreased the viability of these cells. The results show that F127-carried hypericin could be a suitable photosensitizer system to be used in photodynamic therapy against liver tumors, especially if it is photoinduced with red light, which should activate the molecule to a lower extension and prevent damage to the healthy tissue.