Poly(lactic acid) Microparticles Coated with Insulin-Containing Layer-by-Layer Films and Their pH-Dependent Insulin Release

Abstract

Poly(lactic acid) (PLA) microparticles were coated with layer-by-layer (LbL) films containing insulin and the pH-dependent release of insulin was studied. The LbL films were prepared on the surface of PLA microparticles by the alternate deposition of insulin and poly(allylamine hydrochloride) (PAH) through the electrostatic attraction between insulin and PAH. The insulin loading on the PLA microparticles depended on the film thickness, which corresponded to the number of insulin layers, and on the pH of the solution used to deposit insulin. The insulin loading increased with the film thickness and when the film was prepared at pH 7.4. The LbL films decomposed upon exposure to acidic solutions because the electrostatic attraction between the insulin and the PAH in the films disappeared when the charge on insulin changed from negative to positive at an acidic pH, which resulted in the release of insulin. The temperature and salt concentration did not affect the pH stability of the LbL films. The pH threshold for insulin release was pH 5.0-6.0, which corresponds to isoelectric point of insulin, 5.4. The release of insulin from the microparticles was rapid, and was almost complete within a few minutes. The circular dichroism spectra showed that the released insulin retained its original secondary structure. Our insulin-loaded PLA microparticles may be useful for the controlled release of insulin.

Release of Insulin from Calcium Carbonate Microspheres with and without Layer-by-Layer Thin Coatings

“…The unmodified microspheres showed a negative potential, and the potential was reversed upon deposition of first PAH layer because of the positive charge of PAH. The sign of the ζ-potential alternated depending on the sign of electric charges of polymeric materials deposited on the outermost surface of the microspheres, suggesting the successful formation of the LbL film coatings on the surface of the Released Insulin / mg mL -1 Time / min microspheres [28]. It is reasonable to assume that PAH and PSS are deposited on the surface through electrostatic bonds.…”

Tuning protein delivery from different architectures of layer-by-layer assemblies on polymer films

“…[1][2][3][4][5] LbL assembly, complexation between oppositely charged polyelectrolytes, 6 has been applied to a myriad of surfaces (metal, 7 glass, 8 polymers, 9 etc.) and shapes (flat, 1 porous, 9 spherical, 10 etc.). The main applications include drug delivery devices used to incorporate biomolecules of interest 10 or to act as a barrier for sustained release.…”

Voltammetric pH Measurements Using Azure A-Containing Layer-by-Layer Film Immobilized Electrodes

“…Formation of a thin multilayer film can be both driven by electrostatic interaction and by other types of interactions, such as biological affinity, e.g., avidin–biotin bonds [ 2 , 3 , 4 ], sugar–lectin bonds [ 5 ]; hydrogen bonds [ 6 , 7 ]; diol–phenylboronic acid bonds [ 8 , 9 ]; guest–host interactions [ 10 ]; and other low energy physical bonds [ 11 , 12 , 13 ]. Thus, a functional thin film can be formed from synthetic polymers and other materials, such as proteins, such as enzymes [ 14 , 15 ], polysaccharides [ 16 , 17 ], supramolecular compounds [ 18 ], and nanoparticles [ 19 ]. Furthermore, functional molecules can be easily immobilized in a film by modifying them with a polymer chain.…”