title: Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System.
abstract: BACKGROUND
  The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention.
  
  
  METHODS
  Microparticles (MP) were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA), trimethyl-chitosan (TMC), and chitosan (Ch). Using salmon calcitonin (sCT) as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1)-, and Ch-based MP were produced, and their Eudragit L100 (Eud)-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo.
  
  
  RESULTS
  All microparticles before and after enteric coating had a submicron size (600-800 nm) and micrometer size (1300-1500 nm), respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness.
  
  
  CONCLUSIONS
  The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs.
authors.affiliation: Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. onishi@hoshi.ac.jp.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Onishi
authors.affiliation: Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. ri300080-1347@tbz.t-com.ne.jp.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tokuyasu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002116:Calcitonin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002118:Calcium / Q000097:blood*; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D008863:Microspheres; D015394:Molecular Structure; D010316:Particle Size; D051381:Rats
chemical_list: D050071:Bone Density Conservation Agents; C028815:salmon calcitonin; D002116:Calcitonin; D048271:Chitosan; D002118:Calcium
keywords: Eudragit L100-coated microparticles; chitosan-4-thio-butylamidine conjugate microparticles; in vitro release; in vivo efficacy; oral drug delivery system; particle feature; salmon calcitonin