title: Spermidine cross-linked hydrogels as a controlled release biomimetic approach for cloxacillin.
abstract: The intrinsic ability of albumin to bind active substances in the physiological fluids has been explored to endow hydrogels with improved capability to regulate drug release. To develop such biomimetic-functional hydrogels, it is critical that albumin conformation is not altered and that the protein remains retained inside the hydrogel keeping its conformational freedom, i.e., it should be not chemically cross-linked. Thus, the hydrogels were prepared with various proportions of albumin by physical cross-linking of anionic polysaccharides (gellan gum and chondroitin sulfate) with the cationic endogen polyamine spermidine under mild conditions in order to prevent albumin denaturation. Texture and swelling properties of hydrogels with various compositions were recorded, and the effect of the preparation variables was evaluated applying neurofuzzy logic tools for hydrogels prepared with and without albumin and associating the antibiotic cloxacillin. Developed hydrogel systems were extensively analyzed by means of nuclear magnetic resonance (NMR) to determine weak-to-medium and strong binding modes and the equilibrium constants of the albumin-cloxacillin association. NMR techniques were also employed to demonstrate the successful modulation of the cloxacillin release from the albumin-containing hydrogels. In vitro microbiological tests carried out with Staphylococcus aureus and Staphylococcus epidermidis confirmed the interest of the albumin-containing hydrogels as efficient platforms for cloxacillin release in its bioactive form.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela , Campus Vida, 15782 Santiago de Compostela, Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: López-Cebral
authors.forename: Vanessa
authors.initials: V
authors.lastname: Romero-Caamaño
authors.forename: Begoña
authors.initials: B
authors.lastname: Seijo
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
authors.forename: Manuel
authors.initials: M
authors.lastname: Martín-Pastor
authors.forename: Ángel
authors.initials: Á
authors.lastname: Concheiro
authors.forename: Mariana
authors.initials: M
authors.lastname: Landin
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez
mesh_terms: D000418:Albumins / Q000737:chemistry; D032701:Biomimetics / Q000379:methods; D002809:Chondroitin Sulfates / Q000737:chemistry; D003023:Cloxacillin / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D013095:Spermidine / Q000737:chemistry* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
chemical_list: D000418:Albumins; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D002809:Chondroitin Sulfates; D003023:Cloxacillin; D013095:Spermidine