title: Linolenic acid grafted hyaluronan: Process development, structural characterization, biological assessing, and stability studies.
abstract: In this study, hyaluronan (HA) was grafted with alpha-linolenic acid (αLNA) by benzoyl mixed anhydrides methodology, which allowed the derivatization of HA under mild reaction conditions. The reaction was optimized and transferred from laboratory to semi-scale production. The derivative revealed an unexpected cytotoxicity after oven drying and storage at 40°C. For this reason, the storage conditions of sodium linolenyl hyaluronate (αLNA-HA) were optimized in order to preserve the beneficial effect of the derivative. Oven, spray dried and lyophilized samples were prepared and stored at -20°C, 4°C and 25°C up to 6 months. A comprehensive material characterization including stability study of the derivative, as well as evaluation of possible changes on chemical structure and presence of peroxidation products were studied by Nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS), thermogravimetric analysis (TGA) and complemented with assessment of in vitro viability on mouse fibroblasts NIH-3T3. The most stable αLNA-HA derivative was obtained after spray drying and storage at ambient temperature under inert atmosphere. The choice of inert atmosphere is recommended to suppress oxidation of αLNA supporting the positive influence of the derivative on cell viability. The encapsulation of hydrophobic drugs of αLNA-HA were also demonstrated.
authors: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic. Electronic address: huerta-angeles@contipro.com.
authors: Gloria
authors: G
authors: Huerta-Angeles
authors: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors: Martina
authors: M
authors: Brandejsová
authors: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors: Jaromír
authors: J
authors: Kulhánek
authors: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic; Department of Dermatology, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors: Vojtěch
authors: V
authors: Pavlík
authors: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors: Daniela
authors: D
authors: Šmejkalová
authors: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors: Hana
authors: H
authors: Vágnerová
authors: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors: Vladimír
authors: V
authors: Velebný
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004355:Drug Stability; D006820:Hyaluronic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D017962:alpha-Linolenic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D017962:alpha-Linolenic Acid; D006820:Hyaluronic Acid
keywords: Degradation; Encapsulation; Hyaluronic acid; Hyaluronic acid (PubChem CID: 24728612); Linolenic acid (PubChem CID: 5280934); Lipid oxidation; Stability; α-Linolenic acid