1. Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System
- Author
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Ayako Tokuyasu and Hiraku Onishi
- Subjects
Administration, Oral ,02 engineering and technology ,030226 pharmacology & pharmacy ,lcsh:Chemistry ,Chitosan ,chemistry.chemical_compound ,Drug Delivery Systems ,0302 clinical medicine ,particle feature ,lcsh:QH301-705.5 ,oral drug delivery system ,Spectroscopy ,media_common ,Bone Density Conservation Agents ,Molecular Structure ,in vivo efficacy ,General Medicine ,021001 nanoscience & nanotechnology ,Microspheres ,Computer Science Applications ,0210 nano-technology ,Intramuscular injection ,medicine.drug ,Calcitonin ,Drug ,media_common.quotation_subject ,in vitro release ,Nanotechnology ,Absorption (skin) ,Article ,chitosan-4-thio-butylamidine conjugate microparticles ,Eudragit L100-coated microparticles ,salmon calcitonin ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,In vivo ,medicine ,Animals ,Particle Size ,Physical and Theoretical Chemistry ,Molecular Biology ,Chromatography ,Organic Chemistry ,Enteric coating ,In vitro ,Rats ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,Calcium ,Conjugate - 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. Conclusion: The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs.
- Published
- 2016
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