https://orcid.org/0000-0002-7680-8191
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Abstract
Understanding the atomic interaction mechanism between chitosan and insulin at different pH levels is essential in the design of chitosan-based drug-delivery systems. In the present study, insulin-loaded nanoparticles were prepared via ionic gelation of tripolyphosphate (TPP) and chitosan with 76 ± 5.5% encapsulation efficiency. Our results showed that the nanoparticles were spherical with a size of 254 nm. Furthermore, the in vitro release profile of insulin was evaluated for two different pH levels. The release of insulin from nanoparticles after 48 h at pH 4.0 was 92%, compared to 56% at pH 7.4. The kinetics of the release were best fitted by the Weibull equation, which described a burst release in the first five hours followed by a sustained insulin release for up to 48 h. Moreover, we designed a long single chain chitosan (128 kDa)/TPP nanoparticles in real size for the first time and studied the system behavior in acidic and neutral environments using molecular dynamic simulation for 40 nanoseconds (ns). Our results showed that chitosan chains opened more with higher root-mean-square deviation (RMSD) values at pH 4.0 than at pH 7.4. Also, RMSD plots for insulin and TPP molecules showed that insulin molecules diffused away from chitosan chains, and that TPP were randomly dispersed further away from the chitosan chain in an acidic medium than in a neutral one. The in silico studies were in agreement with our in vitro data. Thus self-assembled chitosan/TPP nanoparticles show promise as a means to release protein drugs in acidic environments.
Communicated by Ramaswamy H. Sarma
Disclosure statement
No potential conflict of interest was reported by the authors.