title: Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.
abstract: Interleukin-1beta (IL-1β) is a major cause for induction of various inflammatory mechanisms that are decisively involved to provoke pathogenesis of type 2 diabetes mellitus (T2DM). Interleukin-1 receptor antagonist (IL-1Ra) a naturally occurring anti-inflammatory antagonist of IL-1β has been recently approved for treatment of T2DM but due to its short half-life, higher doses and frequent dosing intervals are required. Pluronic F-127 (PF127) has previously shown to prolong the release of various proteinous drugs and their serum half-lives. Subsequently, in our previous work, we developed a new dosage form of IL-1Ra using PF127 and investigated its in-vitro and in-vivo effects. Here in present work, we have extended this approach using diabetic Goto-kakizaki (GK) rats. We administered IL-1Ra loaded in PF127 gel subcutaneously for one month into GK rats. IL-1Ra loaded in PF127 gel exhibited a sustained and prolonged hypoglycemic effects on treated animals. Intraperitoneal glucose tolerance test (IPGTT) results showed that IL-1Ra loaded in PF127 gel increased glucose tolerance along with increased insulin sensitivity and β-cell's secretory function in treated rats. Moreover, significant reduction in pro-insulin/insulin ratio, lipid profiles and interleukin 6 (IL-6) were also observed. Immunohistochemical analysis showed slight macrophages infiltration in pancreatic islets. Histochemical analysis revealed no PF127-induced alteration in the normal physiology of skin and kidney of treated animals. Hence, we concluded that IL-1Ra loaded in PF127 gel has potential to exhibit broad spectrum anti-inflammatory effects alleviating the symptoms of T2DM.
authors: Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
authors: Muhammad Sajid Hamid
authors: MS
authors: Akash
authors: Kanwal
authors: K
authors: Rehman
authors: Hongying
authors: H
authors: Sun
authors: Shuqing
authors: S
authors: Chen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D005782:Gels; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage* / Q000009:adverse effects; D007515:Islets of Langerhans / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D020442:Poloxamer; D051381:Rats; D012867:Skin / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005782:Gels; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D020442:Poloxamer; C067980:CD68 antigen, human; D000097382:CD68 Molecule