Safety assessment of thiolated polymers: effect on ciliary beat frequency in human nasal epithelial cells

Autor:	Anja Vetter, Thomas F. Palmberger, Andreas Bernkop-Schnürch, Patrick Augustijns
Rok vydání:	2011
Předmět:	Alginates Polymers Pharmaceutical Science Biocompatible Materials Chitosan chemistry.chemical_compound Viscosity Glucuronic Acid Drug Discovery Humans Cilia Sulfhydryl Compounds Administration Intranasal Acrylic acid Pharmacology chemistry.chemical_classification Chromatography Cilium Hexuronic Acids Organic Chemistry Cationic polymerization Epithelial Cells Polymer Apparent viscosity Nasal Mucosa chemistry Covalent bond
Zdroj:	Drug development and industrial pharmacy. 37(12)
ISSN:	1520-5762
Popis:	The aim of this study was to investigate the nasal safety of gel formulations of thiolated polymers (thiomers) by assessing their effect on ciliary beat frequency (CBF) in human nasal epithelial cells.Poly(acrylic acid) 450 kDa-cysteine (PAA-cys) and alginate-cysteine (alg-cys) were synthesized by covalent attachment of L-cysteine to the polymeric backbone. The cationic polymer chitosan-thiobutylamidine (chito-TBA) was synthesized by attaching iminothiolane to chitosan. CBF using was measured by a photometric system. CBF was measured before incubating the cells with test gels, during incubation and after washing out the polymeric test gels to evaluate reversibility of cilio-inhibition. The influence of viscosity on CBF was determined by using hydroxyethylcellulose (HEC)-gels of various concentrations.Ciliary beating was observed to be affected by viscosity, but cilia were still beating in the presence of a HEC-gel displaying an apparent viscosity of 25 Pa.s. In case of thiolated polymers and their unmodified control, a concentration-dependent decrease in CBF could be observed. PAA-cys, alg-cys, chito-TBA and their corresponding unmodified controls exhibited a moderate cilio-inhibitory effect, followed by a partial recovery of CBF when used at a concentration of 1%. Alg-cys 2% and chito-TBA 2% (m/v) gels exhibited severe cilio-inhibition, which was partially reversible. L-cysteine and reduced glutathione led to mild cilio-inhibition at concentrations of 3% (m/v).Taking into account that dilution after application and cilio-modifying effects is usually more pronounced under in vitro conditions, thiomers can be considered as suitable excipients for nasal drug delivery systems.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d08a1d6eb1028f20317456135039b82f https://pubmed.ncbi.nlm.nih.gov/21635138 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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