title: Synthesis of novel amphiphilic hyaluronan containing-aromatic fatty acids for fabrication of polymeric micelles.
abstract: Novel hydrophobized hyaluronan (HA) derivatives, containing ω-phenylalkanoic acids (ω-PAA, 4-phenylbutyric acid, 6-phenylhexanoic, 8-phenyloctanoic or 11-tolylundecanoic acids) were prepared by esterification. Mixed anhydrides obtained after reaction of the carboxyl acid moiety and benzoyl chloride were found to be active acylating agents, affording hydrophobized HA in good yield and under mild conditions. The reactivity of the aromatic fatty acids towards esterification has decreased with the increasing length of the aliphatic spacer between the aromatic substituent and carboxylic acid moiety. The novel HA derivatives self-assembled from very low concentrations and were found to be non-cytotoxic. The potential use of ω-phenylalkanoic acids grafted-HA towards drug delivery applications was demonstrated by hydrophobic drugs (resveratrol and retinyl palmitate) encapsulation. The drug loading capacity of the novel HA derivatives was significantly improved most likely because of π⋯π interactions between the micelle core and loaded hydrophobic aromatic compound.
authors.affiliation: Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic; Department of Chemistry, Faculty of Technology, Tomáš Bat'a University in Zlín, Vavrečkova 275, 760 01 Zlín, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Matelová
authors.affiliation: Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic. Electronic address: huerta-angeles@contipro.com.
authors.forename: Gloria
authors.initials: G
authors.lastname: Huerta-Angeles
authors.affiliation: Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Šmejkalová
authors.affiliation: Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Zdislava
authors.initials: Z
authors.lastname: Brůnová
authors.affiliation: Institute of Organic Chemistry and Technology, Faculty of Chemical Technology University Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Dušek
authors.affiliation: Department of Chemistry, Faculty of Technology, Tomáš Bat'a University in Zlín, Vavrečkova 275, 760 01 Zlín, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Vícha
authors.affiliation: Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Velebný
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D006820:Hyaluronic Acid / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D011108:Polymers / Q000737:chemistry*
chemical_list: D005227:Fatty Acids; D008823:Micelles; D011108:Polymers; D006820:Hyaluronic Acid
keywords: 4-Phenylbutanoic acid (CID 4775); Amphiphilic polysaccharides; Benzoyl chloride (CID 7412); Hyaluronan (CID 24728612); Hyaluronic acid; Resveratrol (CID 445154); Retinyl palmitate (CID 5280531); Topical application; ω-Phenylalkanoic acids