ABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemistry , Chitosan/chemistry , Drug Carriers/chemistry , Endostatins/chemistry , Nanoparticles/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cell Line , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Carriers/pharmacology , Drug Liberation , Endostatins/metabolism , Endostatins/pharmacology , Humans , Microscopy, Electron, Scanning , Particle Size , Peptides/chemistry , Spectroscopy, Fourier Transform InfraredABSTRACT
Cutaneous cancers are among the most common forms of cancer. Melanoma is an aggressive malignancy which is poor in prognosis. Despite of many years of researches, the treatment of melanoma is still a problem. Historically, plants have been main resources in traditional medicine and natural products are considered as important sources of antitumor drugs. Meanwhile, garlic for a long time has been used in man's food as a medicinal plant. In this study, the garlic extract was prepared and fractionated by ultra-filtration method with Amicon system. Garlic extract and its fractions including residue (R) 100, R50, R30, R10, R5, and filtrate (F) 5 were investigated for their cytotoxic activities on Sk-mel3 cell line of melanoma. The results show that garlic extract induced a significant cytotoxic activity on Sk-mel3 cell line. Among fractions R100 and R10 have more potential in cytotoxic activities against Sk-mel3 melanoma cells. In conclusion, garlic appears to be a good candidate as an antitumor agent against melanoma. To clarify the effective molecules and their mechanisms more studies should be applied on animal models and humans.
Subject(s)
Antineoplastic Agents/therapeutic use , Garlic/chemistry , Melanoma/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Skin Neoplasms/drug therapy , Cell Line, Tumor , HumansABSTRACT
The ability of phosphoramidates Me2NP(O)(Cl)(p-NHC6H4NO2) 1, Me2NP(O)(p-NHC6H4NO2)2 2, (CH3C6H4O-p)P(O)(p-NHC6H4NO2)2 3 and (CH3C6H40-p)2P(O)(p-NHC6H4NO2) 4 to inhibit human acetylcholinesterase (hAChE) has been evaluated by a modified Ellman's method and spectrophotometric measurements. Results showed that compounds 1 and 2 do not have any inhibitory potency, whereas compounds 3 and 4 were reversible mixed inhibitors. The IC50 values for inhibitors 3 and 4 were 0.143 and 0.581 mM, respectively. The previously unknown compounds 3 and 4 were synthesized and characterized by 1H, 13C, 31P NMR and IR spectroscopy and elemental analysis.
