Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres

Shuang Wang, Mingsheng Wu, Dan Li, Mingli Jiao, Lan Wang, Haifeng Zhang, Huai Yu Liu, Daifeng Wang, Bing Han

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1898-1906
Number of pages9
JournalBiological and Pharmaceutical Bulletin
Volume35
Issue number11
DOIs
StatePublished - Nov 2012
Externally publishedYes

Keywords

  • In vivo release
  • Lanreotide
  • Microsphere
  • Poly(lactic-co-glycolic acid)
  • Safety
  • Toxicology

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

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