3 years ago

Controlled release of an endostatin peptide using chitosan nanoparticles

Controlled release of an endostatin peptide using chitosan nanoparticles
Taher Droudi, Peirhosein Kolivand, Ahmad Reza Esmaeili Rastaghi, Sanaz Ebrahimi Samani, Khosro Khajeh, Hadi Kazemi, Zahra Seraj, Hossein Naderimanesh, S. Mohsen Asghari
Whereas several anticancer peptides are in different stages of clinical development, their administration is limited by the fast elimination from the systemic circulation. Peptide loading on nano-carriers can pave the way for their future application. We have recently indicated that a disulfide loop rather than a Zn-binding loop improves the anti-angiogenic and antitumor activities of the N-terminal fragment of endostatin. In this study, chitosan nanoparticles (CS NPs) are used for the controlled release of the engineered peptide. Loading of the peptide into CS NPs using the ionic gelation method was confirmed by FTIR and resulted in final particle size, poly-dispersity index and surface charge of 186.5 ± 24.0 nm, 0.26 ± 0.02 and 20.1 ± 0.4 mV respectively. The SEM morphological analysis revealed spherical particles with an average size of 80 ± 5 nm. Peptide loading studies revealed that CS NPs are able to adsorb the peptide as ~70%. The release measurements indicated an initial burst release by 49% after 2 hr and complete release after 80 hr. According to in vitro studies, the loaded peptide was much more toxic for endothelial cells than different cancer cell lines. These results underscore the promise of CS NPs as therapeutics nanosystems and open a perspective for improving the clinical applications of peptide drugs. Application of anticancer peptides is limited by fast elimination from the systemic circulation. In this study, chitosan nanoparticles are used for the controlled release of an engineered antiangiogenic peptide derived from the N-terminal fragment of human endostatin. The nanoparticles were characterized before and after peptide loading by FTIR, zeta sizer and SEM. Our measurements revealed that chitosan nanoparticles are able to adsorb the peptide as ~70% and complete release took place after 80 h. According to in vitro studies, the loaded peptide was much more toxic for endothelial cells than cancer cell lines. These results underscore the promise of chitosan nanoparticles as therapeutics nanosystems.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.12959

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