title: Chondroitin-based nanoplexes as peptide delivery systems--Investigations into the self-assembly process, solid-state and extended release characteristics.
abstract: A new type of self-assembled polyelectrolyte complex nanocarrier composed of chondroitin (CHON) and protamine (PROT) was designed and the ability of the carriers to bind salmon calcitonin (sCT) was examined. The response of sCT-loaded CHON/PROT NPs to a change in the properties of the liquid medium, e.g. its pH, composition or ionic strength was studied and in vitro peptide release was assessed. The biocompatibility of the NPs was evaluated in Caco-2 cells. CHON/PROT NPs were successfully obtained with properties that were dependent on the concentration of the polyelectrolytes and their mixing ratio. X-ray diffraction determined the amorphous nature of the negatively charged NPs, while those with the positive surface potential were semi-crystalline. sCT was efficiently associated with the nanocarriers (98-100%) and a notably high drug loading (13-38%) was achieved. The particles had negative zeta potential values and were homogenously dispersed with sizes between 60 and 250 nm. CHON/PROT NPs released less than 10% of the total loaded peptide in the first hour of the in vitro release studies. The enthalpy of the decomposition exotherm correlated with the amount of sCT remaining in NPs after the release experiments. The composition of medium and its ionic strength was found to have a considerable influence on the release of sCT from CHON/PROT NPs. Complexation to CHON markedly reduced the toxic effects exerted by PROT and the NPs were compatible and well tolerated by Caco-2 cells.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland; INSERM U1066, Micro et Nanomédecines Biomimétiques, Angers, France.
authors.forename: Anita
authors.initials: A
authors.lastname: Umerska
authors.affiliation: Bradford School of Pharmacy, Centre for Pharmaceutical Engineering Science, Faculty of Life Sciences, University of Bradford, Richmond Rd., BD71DP Bradford, W.Yorks., UK.
authors.forename: Krzysztof Jan
authors.initials: KJ
authors.lastname: Paluch
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland; School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Santos-Martinez
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Carlos
authors.initials: C
authors.lastname: Medina
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Owen I
authors.initials: OI
authors.lastname: Corrigan
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland. Electronic address: lidia.tajber@tcd.ie.
authors.forename: Lidia
authors.initials: L
authors.lastname: Tajber
mesh_terms: D018938:Caco-2 Cells; D002116:Calcitonin / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002807:Chondroitin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D050997:Nanomedicine; D053758:Nanoparticles; D009994:Osmolar Concentration; D011479:Protamines / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011485:Protein Binding; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011479:Protamines; C028815:salmon calcitonin; D002116:Calcitonin; D002807:Chondroitin
keywords: Biocompatibility; Caco-2 cells; Calcitonin; Chondroitin; Nanoparticles; Peptide delivery; Polyelectrolyte complex; Protamine; Toxicity