title: Hybrid nanosystems based on natural polymers as protein carriers for respiratory delivery: Stability and toxicological evaluation.
abstract: Chitosan/carrageenan/tripolyphosphate nanoparticles were previously presented as holding potential for an application in transmucosal delivery of macromolecules, with tripolyphosphate demonstrating to contribute for both size reduction and stabilisation of the nanoparticles. This work was aimed at evaluating the capacity of the nanoparticles as protein carriers for pulmonary and nasal transmucosal delivery, further assessing their biocompatibility pattern regarding that application. Nanoparticles demonstrated stability in presence of lysozyme, while freeze-drying was shown to preserve their characteristics when glucose or sucrose were used as cryoprotectants. Bovine serum albumin was associated to the nanoparticles, which were successfully microencapsulated by spray-drying to meet the aerodynamic requirements inherent to pulmonary delivery. Finally, a satisfactory biocompatibility profile was demonstrated upon exposure of two respiratory cell lines (Calu-3 and A549 cells) to the carriers. A negligible effect on cell viability along with no alterations on transepithelial electrical resistance and no induction of inflammatory response were observed.
authors.affiliation: CBME - Centre for Molecular and Structural Biomedicine/IBB - Institute for Biotechnology and Bioengineering, University of Algarve, Faculty of Sciences and Technology, Campus de Gambelas, 8005-139 Faro, Portugal. Electronic address: susananasus@gmail.com.
authors.forename: Susana
authors.initials: S
authors.lastname: Rodrigues
authors.affiliation: Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal; CEAUL - Center of Statistics and Applications, Faculty of Sciences, University of Lisbon, Campo Grande, 1749-016 Lisboa, Portugal; CESUAlg - Centre for Research and Development in Health, University of Algarve, Portugal. Electronic address: ccordei@ualg.pt.
authors.forename: Clara
authors.initials: C
authors.lastname: Cordeiro
authors.affiliation: NanoBioFar Group, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain. Electronic address: mbegona.seijo@usc.es.
authors.forename: Begoña
authors.initials: B
authors.lastname: Seijo
authors.affiliation: NanoBioFar Group, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain. Electronic address: mdelcarmen.remunan@usc.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Remuñán-López
authors.affiliation: CBME - Centre for Molecular and Structural Biomedicine/IBB - Institute for Biotechnology and Bioengineering, University of Algarve, Faculty of Sciences and Technology, Campus de Gambelas, 8005-139 Faro, Portugal. Electronic address: amgrenha@ualg.pt.
authors.forename: Ana
authors.initials: A
authors.lastname: Grenha
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D002351:Carrageenan / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D003451:Cryoprotective Agents / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004339:Drug Compounding; D005612:Freeze Drying; D006801:Humans; D009005:Monosaccharides / Q000737:chemistry; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry*; D011122:Polyphosphates / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D003451:Cryoprotective Agents; D004337:Drug Carriers; D009005:Monosaccharides; D011108:Polymers; D011122:Polyphosphates; D012710:Serum Albumin, Bovine; D002351:Carrageenan; D048271:Chitosan; D009113:Muramidase; C005692:triphosphoric acid
keywords: Biocompatibility; Microencapsulation; Nanoparticles; Nasal delivery; Protein delivery; Pulmonary delivery