title: Nanoparticulate assembly of mannuronic acid- and guluronic acid-rich alginate: oral insulin carrier and glucose binder.
abstract: The relationship of high and low molecular weight mannuronic acid (M)- and guluronic acid (G)-rich alginate nanoparticles as oral insulin carrier was elucidated. Nanoparticles were prepared through ionotropic gelation using Ca(2+) , and then in vitro physicochemical attributes and in vivo antidiabetic characteristics were examined. The alginate nanoparticles had insulin release retarded when the matrices had high alginate-to-insulin ratio or strong alginate-insulin interaction via OH moiety. High molecular weight M-rich alginate nanoparticles were characterized by assemblies of long polymer chains that enabled insulin encapsulation with weaker polymer-drug interaction than nanoparticles prepared from other alginate grades. They were able to encapsulate and yet release and have insulin absorbed into systemic circulation, thereby lowering rat blood glucose. High molecular weight G- and low molecular weight M-rich alginate nanoparticles showed remarkable polymer-insulin interaction. This retarded the drug release and negated its absorption. Blood glucose lowering was, however, demonstrated in vivo with insulin-free matrices of these nanoparticles because of the strong alginate-glucose binding that led to intestinal glucose retention. Alginate nanoparticles can be used as oral insulin carrier or glucose binder in the treatment of diabetes as a function of its chemical composition. High molecular weight M-rich alginate nanoparticles are a suitable vehicle for future development into oral insulin carrier.
authors.affiliation: Non-Destructive Biomedical and Pharmaceutical Research Centre, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia; Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia.
authors.forename: Aminah
authors.initials: A
authors.lastname: Kadir
authors.forename: Mohammad Tarmizi Mohd
authors.initials: MT
authors.lastname: Mokhtar
authors.forename: Tin Wui
authors.initials: TW
authors.lastname: Wong
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004337:Drug Carriers / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000464:Alginates; D001786:Blood Glucose; D004337:Drug Carriers; D006603:Hexuronic Acids; D007004:Hypoglycemic Agents; D007328:Insulin; C007896:guluronic acid; D020723:Glucuronic Acid; C008324:mannuronic acid
keywords: alginate; diabetes mellitus; dissolution; insulin; intestinal absorption; nanoparticles; oral drug delivery; polymeric drug carrier; polymeric drug delivery system; protein delivery