Poly(lactic acid) microparticles coated with insulin-containing layer-by-layer films and their pH-dependent insulin release.

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.

Layer-by-layer films composed of poly(allylamine) and insulin for pH-triggered release of insulin.

Layer-by-layer (LbL) thin films containing insulin were prepared by alternately depositing insulin and poly(allylamine hydrochloride) (PAH) onto a solid surface at pH 7.4. The deposition behavior of the LbL films was studied using a quartz crystal microbalance, UV-vis absorption spectrometer, ζ-potential analyzer, and an atomic force microscope. The insulin-containing LbL films were stable in neutral pH media, but the films decomposed in solutions at pH 5.0 or lower. The decomposition of the LbL films can be rationalized on the basis of the loss of electrostatic interactions between insulin and PAH due to a shift in the net electric charge of insulin from negative to positive in acidic media. The films also decomposed to some extent in media at pH 9.0 and 10. A circular dichroism analysis showed that insulin retained its original conformation when released from LbL film into acidic solutions.

Insulin-containing layer-by-layer films deposited on poly(lactic acid) microbeads for pH-controlled release of insulin.

Layer-by-layer (LbL) thin films containing insulin were deposited on the surface of biodegradable poly(lactic acid) (PLA) microbeads and the pH-triggered release of insulin was studied. The LbL films were successfully prepared by the alternate deposition of insulin and poly(vinyl sulfate) (PVS) or dextran sulfate (DS) at pH 4.0 through the electrostatic force of attraction between positively charged insulin and polyanions. The loading of insulin on the microbeads was dependent on the number of insulin layers and the type of polyanions used; higher insulin loading was observed for thicker films and when PVS was used as the polyanion. Insulin was released from the microbeads when they were exposed to neutral solution (pH 7.4) due to a loss of electrostatic attraction between the insulin and polyanions in the films, which in turn was caused by the charge reversal of insulin from positive to negative in the neutral medium. The pH threshold for insulin release was found to be pH 5.0-6.0. The released insulin retained its original secondary structure as evidenced by circular dichroism spectra. The insulin loaded on the microbeads was satisfactorily stable even in the presence of a digestive enzyme (pepsin) at pH 1.5. These results suggest a potential future use for insulin-loaded microbeads in the oral delivery of insulin.