title: Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation.
abstract: In this work, we sought to generate sustained-release injectable microspheres loaded with the GLP-1 analogue liraglutide. Using water-in-oil-in-water double emulsion methods, poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with liraglutide were prepared. The microspheres gave sustained drug release over 30days, with cumulative release of up to 90% reached in vitro. The microspheres were further studied in a rat model of diabetes, and their performance compared with a group given daily liraglutide injections. Reduced blood sugar levels were seen in the microsphere treatment groups, with the results being similar to those obtained with conventional injections between 10 and 25days after the commencement of treatment. After 5 and 30days of treatment, the microspheres seem a little slower to act than the injections. The pathology of the rats' spleen, heart, kidney and lungs was probed after the 30-day treatment period, and the results indicated that the microspheres were safe and had beneficial effects on the liver, reducing the occurrence of fatty deposits seen in untreated diabetic rats. Moreover, in terms of liver, renal and cardiac functions, and blood lipid and antioxidant levels, the microspheres were as effective as the injections. The expression of several proteases linked to the metabolism of aliphatic acids and homocysteine was promoted by the microsphere formulations. Inflammatory markers in the microsphere treatment groups were somewhat higher than the injection group, however. The liraglutide/PLGA microspheres prepared in this work are overall shown to be efficacious in a rat model of diabetes, and we thus believe they have strong potential for clinical use.
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China.
authors.forename: Junzi
authors.initials: J
authors.lastname: Wu
authors.affiliation: UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Williams
authors.affiliation: Faculty of Life Sciences & Computing, London Metropolitan University, London N7 8DB, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Branford-White
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China.
authors.forename: Heyu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Geriatrics, The First People's Hospital of Yunnan Province, Yunnan 650034, PR China. Electronic address: liyanken@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China. Electronic address: lzhu@dhu.edu.cn.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006442:Glycated Hemoglobin / Q000032:analysis; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000737:chemistry*; D000069450:Liraglutide / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D019344:Lactic Acid; D000069450:Liraglutide; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
keywords: Liraglutide; Microspheres; Poly(lactide-co-glycolide); Type 2 diabetes mellitus; Water in oil in water