title: Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors.
abstract: We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3-6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.
authors.affiliation: Cardiovascular Medicine, Tianjin First Center Hospital, Tianjin 300192, China. l-long@126.com.
authors.forename: Xuying
authors.initials: X
authors.lastname: Ye
authors.affiliation: Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China. yinzi490@163.com.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Yin
authors.affiliation: Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China. luyu507@aliyun.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China. hbziqing@163.com.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China. wanghan87816@126.com.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
mesh_terms: D061605:Administration, Intravenous; D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D006415:Hematoporphyrins / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D011524:Protoporphyrins / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000188:drug therapy*; D013488:Suppositories / Q000008:administration & dosage / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D006415:Hematoporphyrins; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D013488:Suppositories; C494379:hematoporphyrin monomethyl ether; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-aminolevulinic acid; drug delivery; hematoporphyrin monomethyl ether; photodynamic therapy; photosensitizer; rectal cancer