Preparation, intestinal segment stability, and mucoadhesion properties of novel thymopentin-loaded chitosan derivatives coated with poly (n-butyl) cyanoacrylate nanoparticles.

Background: In order to develop a promising carrier for the oral delivery of proteins and peptide drugs, a novel bioadhesive nanocarrier of chitosan (CTS) derivatives coated with poly (n-butyl) cyanoacrylate nanoparticles (PBCA-NPs) was prepared in this study.

Methods: Three different thymopentin (TP5)-loaded nanoparticles were prepared in the present study. TP5-PBCA-NPs were developed by modifying an emulsion polymerization method, and CTS and chitosan-glutathione (CG) derivative-coated PBCA nanoparticles were obtained from the electrostatic interactions between CTS or CG with negatively charged PBCA nanoparticles.

Results: The particle sizes of TP5-PBCA-NPs, TP5-CTS-PBCA-NPs, and TP5-CG-PBCA-NPs were 212.3±6.9, 274.6±8.2, and 310.4±7.5 nm, respectively, while the respective zeta potentials were -22.6±0.76, 23.3±1.2, and 34.6±1.6 mV with encapsulation efficiencies of 79.37%±2.15%, 74.21%±2.13%, and 72.65%±1.48%, respectively. An everted intestinal ring method indicated that drug stability was remarkably improved after incorporation into the nanoparticles, especially the CG-coated nanoparticles. The mucus layer retention rates for CTS- and CG-coated nanoparticles were 1.43 and 1.83 times that of the uncoated nanoparticles, respectively, using ex vivo mucosa. The in vivo mucoadhesion study illustrated that the transfer of uncoated PBCA-NPs from the stomach to the intestine was faster than that of CTS-PBCA-NPs and CG-PBCA-NPs, while the CG-PBCA-NPs presented the best intestinal retentive characteristic.

Conclusion: In summary, this study demonstrated the feasibility and benefit of orally delivering peptide drugs using novel CTS derivative-coated nanoparticles with optimal stability and bioadhesive properties.