Protein Capsules with Cross‐Linked, Semipermeable, and Enzyme‐Degradable Surface Barriers for Controlled Release

Abstract

This paper describes a method for fabricating protein-based capsules with semipermeable and enzyme-degradable surface barriers. It involves the use of a simple fluidic device to generate water-in-oil emulsion droplets, followed by cross-linking of proteins at the water-oil interface to generate a semipermeable surface barrier. The capsules can be readily fabricated with uniform and controllable sizes and, more importantly, show selective permeability toward molecules with different molecular weights: small molecules like fluorescein sodium salt can freely diffuse through the surface barrier while macromolecules such as proteins can not. The proteins, however, can be released by digesting the surface barrier with an enzyme such as pepsin. Taken together, the capsules hold great potential for applications in controlled release, in particular, for the delivery of protein drugs.

Microfluidic fabrication of microparticles for biomedical applications

“…For instance, fluorescein sodium salt (Mw = 376 Da) encapsulated inside a protein-based microcapsules is released 60% in 1 h, because of its smaller size compared to the mesh size of the microcapsule membrane. 165 By contrast, large FITC-bovine serum albumin (BSA) (Mw = 68,000 Da) almost does not leak within the same period. For a microcapsule membrane composed of polyelectrolytes, 113 the release time is extended significantly, from 10 to 1000 min, when the molecular weight of neutral dextran molecules increases from 5 to 40 kDa.…”

“…15e). 165 Microcapsules with a shell membrane composed of 15-crown-5, NiPAM, and AAm-based copolymer can recognize K + ion to form a sandwich complex and induce phase transition of PNiPAM. The capsules shrink and rupture rapidly, leading to the ejection of all the encapsulated lipophilic actives in the cores.…”

“…e) The enzyme-triggered release of protein-based microcapsules and the release profile of the FITC-BSA. 165 Reprinted with permission from ref. 165.…”

Microfluidic fabrication of hollow protein microcapsules for rate-controlled release

“…For encapsulation applications, microuidic platforms provide precise particle size control over a wide range, which is vital for ensuring product homogeneity. 8 Microuidic platforms have been reported for single-step processes for fabricating many sophisticated supramolecular microcapsules, for example, nonspherical particles, 11 porous microcapsules, 12 alginate microspheres, 13 dendritic microcapsules, 14 cross-linked protein capsules 15 and biological microgels. 16 Microuidic chips have also been deployed to trigger precisely controlled interfacial reactions for fabricating complex and multiple emulsions.…”

Biopolymer Microparticles Prepared by Microfluidics for Biomedical Applications

“…Albumin is a globular protein that is moderately soluble in salt solutions and denatured upon heat treatment . Albumin microcapsules have been fabricated for the controlled delivery of protein drugs by chemical crosslinking of BSA at the water–oil interface of emulsion droplets . The resultant BSA microcapsules were characterized by the semipermeable surface barriers which permit free diffusion of small molecules like fluorescent sodium salt but not of macromolecules like fluorescent BSA.…”