Preparation and in vitro and in vivo release of ALA and HMME hydrogel suppository

Abstract

Objective To prepare 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) hydrogel suppositories and to evaluate their photosensitizer transfer efficiencies in rectal tumor tissue. Methods The BALB/c mice implanted SW837 rectal cancer cells subcutaneously were randomly divided into four groups: intrarectal suppository administration group, cutaneous administration group, intratumoral injection group and intravenous injection group. Fluorescence spectrophotometry was used to measure the concentration of protoporphyrin Ⅸ (PpⅨ) and HMME in rectal wall, skin and tumor tissue. The distribution of photosensitizer was determined by a fluorescence spectroscopy system. Results The concentration of PpⅨ in the ALA suppository administration group was 9.76 times (1 h) and 5.80 times (3 h) higher than that in the cutaneous administration group, and the differences were statistically significant (all P<0.05). The maximal penetration depth of ALA in tumor tissue was about 3-6 mm at 2 h after the cutaneous administration. After the HMME suppository administration, the concentration of HMME in the rectal wall was very low. The maximal penetration depth of HMME in tumor tissue was less than 2 mm after the cutaneous administration. Conclusions ALA is more likely to penetrate mucosal barrier compared to skin tissue. The hydrogel suppository based rectal administration is expected to be a new administration method for the rectal cancer photodynamic therapy using ALA. Key words: Photosensitizer; Drug delivery; Photodynamic therapy; HMME; ALA; Rectal cancer