title: Nanoparticles of cationic chimeric peptide and sodium polyacrylate exhibit striking antinociception activity at lower dose.
abstract: The current study investigates the performance of polyelectrolyte complexes based nanoparticles in improving the antinociceptive activity of cationic chimeric peptide-YFa at lower dose. Size, Zeta potential and morphology of the nanoparticles were determined. Size of the nanoparticles decreases and zeta potential increases with concomitant increase in charge ratio (Z(+/-)). The nanoparticles at Z(+/-)12 are spherical with 70+/-7 nm diameter in AFM and displayed positive surface charge and similar sizes (83+/-8 nm) by Zetasizer. The nanoparticles of Z(+/-) 12 are used in this study. Cytotoxicity by MTT assay on three different mammalian cell lines (liver, neuronal and kidney) revealed lower toxicity of nanoparticles. Hematological parameters were also not affected by nanoparticles compared to normal counts of water treated control group. Nanoparticles containing 10 mg/kg YFa produced increased antinociception, approximately 36%, in tail-flick latency test in mice, whereas the neat peptide at the same concentration did not show any antinociception activity. This enhancement in activity is attributed to the nanoparticle associated protection of peptide from proteolytic degradation. In vitro peptide release study in plasma also supported the antinociception profile of nanoparticles. Thus, our results suggest of a potential nanoparticle delivery system for cationic peptide drug candidates for improving their stability and bioavailability.
authors.affiliation: Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Gupta
authors.forename: Vijay P
authors.initials: VP
authors.lastname: Singh
authors.forename: Raj K
authors.initials: RK
authors.lastname: Kurupati
authors.forename: Anita
authors.initials: A
authors.lastname: Mann
authors.forename: Munia
authors.initials: M
authors.lastname: Ganguli
authors.forename: Yogendra K
authors.initials: YK
authors.lastname: Gupta
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
authors.forename: Kishwar
authors.initials: K
authors.lastname: Saleem
authors.forename: Santosh
authors.initials: S
authors.lastname: Pasha
authors.forename: Souvik
authors.initials: S
authors.lastname: Maiti
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry / Q000633:toxicity; D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D008322:Mammals; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D013623:Tail / Q000187:drug effects
chemical_list: D000180:Acrylic Resins; D000700:Analgesics; D002412:Cations; D010455:Peptides; C006903:carbopol 940