Tuneable semi-synthetic network alginate for absorptive encapsulation and controlled release of protein therapeutics.
Stimuli-responsive hydrogels swell or contract in response to external pH, ionic strength or temperature, and are of considerable interest as pharmaceutical controlled release devices. Alginate, a mucoadhesive biopolymer, was used as building block in the semi-synthesis of a tetra-functional acetal-linked networked polymer (SNAP) with carboxylate moieties preserved as stimuli-responsive sensors and tuneable pore sizes larger than the hydrodynamic radius of model molecules ranging between 1 and 540 kDa. Based on the diffusion coefficients calculated from protein uptake experiments, the networked polymer with pre-designed pore size of 80 nm can allow vitamin B(12), lysozyme, subtilisin, insulin, albumin, and urease to diffuse freely into the hydrogel with diffusivity ratio of D(gel)/D(water) (diffusion coefficients in hydrogel to water) between 0.60 and 0.95. Drying was applied as post-fabrication modification to alter/control the diffusional properties of the gel matrix. Together with the pH-responsive swelling properties, SNAP granules containing acid-labile protein therapeutics such as insulin showed protective characteristics by retaining collapsed/compact state in gastric environment (pH˜1.2) while swelling in neutral pH to release the bioactives at near zero-order kinetics. SNAP, a new class of tuneable biomaterial, can be semi-synthesized with desired pore properties, which when applied with the absorptive encapsulation technique, can serve as a technology platform for oral delivery of biomolecules with wide range of molecular sizes.
Chan
Ariel W
AW
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada.
Neufeld
Ronald J
RJ
D000042:Absorption / Q000187:drug effects; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion / Q000187:drug effects; D005782:Gels; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007700:Kinetics; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry; D016062:Porosity / Q000187:drug effects; D011506:Proteins / Q000627:therapeutic use*; D012996:Solutions
D000464:Alginates; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005782:Gels; D011108:Polymers; D011506:Proteins; D012996:Solutions