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|Title:||Formulation pH modulates the interaction of insulin with chitosan nanoparticles|
|Citation:||Zengshuan, Ma., Yeoh, H.H., Lim, L.-Y. (2002). Formulation pH modulates the interaction of insulin with chitosan nanoparticles. Journal of Pharmaceutical Sciences 91 (6) : 1396-1404. ScholarBank@NUS Repository. https://doi.org/10.1002/jps.10149|
|Abstract:||Previous studies on chitosan-insulin nanoparticles have reported diverse encapsulation efficiency and insulin release profiles despite similar formulation and preparation procedures. This study examined the efficiency and mechanism of association of insulin with chitosan nanoparticles in the pH range of 2.3 to 6.3. Nanoparticles of 237 to 253 nm were prepared by ionotropic gelation of chitosan with tripolyphosphate counterions. Insulin was quantified by an RP-HPLC method. The insulin association efficiency (AE) spanned a broad range from 2 to 85%, and was highly sensitive to formulation pH. Highest AE was measured at insulin loading concentrations ≥ 4.28 U/mL and pH 6.1, close to the pI of native insulin and the pKa of chitosan. This association, attributed to physical adsorption of insulin through hydrophobic interactions with chitosan, was labile, and the associated insulin rapidly and completely released by dilution of the nanoparticles in aqueous media of pH 2 to 7.4. AE obtained at pH 5.3 was less than half that measured at pH 6.1 at corresponding insulin concentration, but the association at pH 5.3 appeared to be based on stronger interactions, because the release of insulin was pH-dependent and recovery was less than 25% even upon disintegration of the chitosan matrix. Interaction of insulin with the chitosan nanoparticles rendered the protein more susceptible to acid and enzymatic hydrolyses, the effects being more predominant in nanoparticles prepared at pH 5.3 than at pH 6.1. © 2002 Wiley-Liss, Inc.|
|Source Title:||Journal of Pharmaceutical Sciences|
|Appears in Collections:||Staff Publications|
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