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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Binding, Competitive
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Biological Transport / drug effects
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Boronic Acids / chemistry*
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Boronic Acids / metabolism
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Boronic Acids / pharmacology
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Cell Survival / drug effects
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Concanavalin A / chemistry
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Concanavalin A / metabolism
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Dextrans / pharmacology
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Dose-Response Relationship, Drug
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Drug Carriers / chemistry*
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Drug Carriers / metabolism
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Drug Carriers / pharmacology
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Drug Combinations
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Drug Delivery Systems / methods*
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Glucose / metabolism
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Glucose / pharmacology
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HeLa Cells
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Humans
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Immunohistochemistry
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Insulin / administration & dosage*
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Insulin / chemistry
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Insulin / pharmacokinetics
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Lipids / chemistry
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Liposomes / chemistry
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Molecular Structure
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NF-kappa B / metabolism
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Nanoparticles / chemistry
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Polyethylene Glycols / chemistry
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Sodium Chloride / pharmacology
Substances
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Boronic Acids
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Dextrans
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Drug Carriers
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Drug Combinations
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Insulin
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Lipids
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Liposomes
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NF-kappa B
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dextran - saline drug combination
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Concanavalin A
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Polyethylene Glycols
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Sodium Chloride
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Glucose