title: Novel pH-sensitive lipid-polymer composite microspheres of 10-hydroxycamptothecin exhibiting colon-specific biodistribution and reduced systemic absorption.
abstract: Novel lipid-polymer composite microspheres (LP-MS) were prepared by combining pH-sensitive polymer Eudragit S100 with solid lipid Compritol 888 ATO for colonic delivery of 10-hydroxycamptothecin (HCPT), and pH-dependent controlled drug release has been achieved. The colon-specific biodistribution and uptake by the mucosal tissue were examined using coumarin-6-marked LP-MS. It is proved that good in vitro-in vivo relationship has been achieved, with more drugs being delivered to colon and a higher drug level was maintained for a long period. Moreover, in vivo bioavailability of LP-MS was evaluated with conventional enteric microspheres (enteric MS) as reference. After administration of LP-MS, systemic absorption of HCPT was greatly reduced, with area under the curve from 0 to 24h (AUC0-24 h , 2.186 ± 0.27) being significantly lower than that of enteric MS group (6.352 ± 0.696). In conclusion, the novel pH-sensitive LP-MS has potential for colon-specific drug delivery.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gan
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Xuhui District Central Hospital, Shanghai 200031, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Gao
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Chun-Liu
authors.initials: CL
authors.lastname: Zhu
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: simm2122@vip.sina.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gan
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D051381:Rats
chemical_list: D000180:Acrylic Resins; D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D005227:Fatty Acids; C086409:glyceryl behenate; C050528:Eudragit RS; C028098:10-hydroxycamptothecin; D002166:Camptothecin