title: Non inflammatory boronate based glucose-responsive insulin delivery systems.
abstract: Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT). This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA), a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L). The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.
authors.affiliation: School of Biomedical Informatics, The University of Texas Health Sciences Center at Houston, Houston, Texas, United States of America.
authors.forename: Indrani
authors.initials: I
authors.lastname: Dasgupta
authors.forename: Eric A
authors.initials: EA
authors.lastname: Tanifum
authors.forename: Mayank
authors.initials: M
authors.lastname: Srivastava
authors.forename: Sharangdhar S
authors.initials: SS
authors.lastname: Phatak
authors.forename: Claudio N
authors.initials: CN
authors.lastname: Cavasotto
authors.forename: Mostafa
authors.initials: M
authors.lastname: Analoui
authors.forename: Ananth
authors.initials: A
authors.lastname: Annapragada
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D001897:Boronic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000737:chemistry / Q000378:metabolism; D003911:Dextrans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D001897:Boronic Acids; D003911:Dextrans; D004337:Drug Carriers; D004338:Drug Combinations; D007328:Insulin; D008055:Lipids; D008081:Liposomes; D016328:NF-kappa B; C049389:dextran - saline drug combination; D003208:Concanavalin A; D011092:Polyethylene Glycols; D012965:Sodium Chloride; D005947:Glucose