title: Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres.
abstract: The goal of this project was to prepare long-acting lanreotide acetate poly(lactic-co-glycolic acid) (PLGA) microspheres and to analyze the in vivo and in vitro release, safety and toxicology of these preparations. Long-acting lanreotide acetate PLGA microspheres that exhibited a 5-week slow-release period were prepared by a multiple-emulsion solvent evaporation method. Physical characterization, as well as the analysis of the in vivo and in vitro release, safety, acute toxicity and chronic toxicity of the lanreotide microspheres, were conducted in animal models in rats, guinea pigs, rabbits and beagle dogs. The lanreotide acetate PLGA microspheres prepared by multiple-emulsion solvent evaporation had smooth surfaces, uniform particle size and stable lanreotide loading. In vivo and in vitro experiments showed that the lanreotide acetate PLGA microspheres could continuously release lanreotide for 5 weeks. The safety of these long acting lanreotide microspheres was good in the following animal models: active systemic anaphylaxis test in guinea pigs, passive cutaneous anaphylaxis test in rats, hemolytic test in rabbits, local skin irritation test after subcutaneous administration in rabbits and muscle stimulation test in rabbits. Furthermore, no significant acute toxicity or chronic toxicity was observed after administration of lanreotide acetate PLGA microspheres in beagle dogs at dosages up to 22 mg/kg. The lanreotide acetate PLGA microspheres that were prepared in this study exhibited beneficial characteristics in apparent property and structural stability, as well as in release trends in vivo and in vitro.
authors.affiliation: China Japan Union Hospital, Jilin University, Changchun 130033, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Mingli
authors.initials: M
authors.lastname: Jiao
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Liu
authors.forename: Daifeng
authors.initials: D
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Han
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000633:toxicity*; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008863:Microspheres; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D051381:Rats; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D010456:Peptides, Cyclic; C060347:lanreotide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013004:Somatostatin