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ALA和HMME水凝胶栓剂的制备和体内外释药研究

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

摘要:

目的 制备光敏剂5-氨基酮戊酸(ALA)和血卟啉单甲醚(HMME)水凝胶栓剂,评价其对直肠肿瘤组织的光敏剂递送效率.方法 将皮下移植人直肠癌细胞SW837的BALB/c小鼠随机分为水凝胶栓剂直肠局部给药组、皮肤局部给药组、瘤内注射给药组和静脉注射给药组.用荧光光谱仪测量直肠壁、皮肤和皮下肿瘤中原卟啉(PpⅨ)和HMME的浓度,荧光光谱系统测定相应的光敏剂分布情况.结果 ALA水凝胶栓剂直肠局部给药组的PpⅨ浓度分别是皮肤局部给药组的9.76倍(1 h)和5.80倍(3 h),差异均具有统计学意义(均P<0.05).皮肤局部给药后2h,ALA在肿瘤组织内达到最大穿透深度(3~6 mm).而HMME水凝胶栓剂直肠局部给药后,直肠壁中的HMME浓度极低,且皮肤局部给药后的最大肿瘤穿透深度不足2 mm.结论 与皮肤相比,ALA更易穿透黏膜屏障,以水凝胶栓剂形式直肠局部给药有望成为ALA用于光动力疗法治疗直肠癌的一种给药方式.

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abstracts:

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.

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