title: Melatonin-loaded chitosan/Pluronic® F127 microspheres as in situ forming hydrogel: An innovative antimicrobial wound dressing.
abstract: The aim of this study was to develop melatonin-loaded chitosan based microspheres as dry powder formulation suitable for wound dressing, rapidly forming hydrogel in contact with wound exudate. Microspheres were produced by spray-drying method. Fractional factorial design was employed to elucidate the effect of formulation and process parameters (feed flow rate, inlet air temperature, chitosan concentration, chitosan/melatonin ratio and chitosan/Pluronic® F127 ratio) on the product characteristics related to process applicability (production yield, entrapment efficiency and product moisture content) and microsphere performance in biological environment (microsphere mean diameter and surface charge). Appropriate formulation and process parameters for the establishment of efficient drying process resulting in fine-tuned chitosan and chitosan/Pluronic® F127 microspheres (efficient melatonin encapsulation, small diameter positive surface charge and low moisture content) were identified. Microspheres were characterized by appropriate flowability and high rate and extent of fluid uptake. Incorporation of Pluronic® F127 in microsphere matrix resulted in high melatonin amorphization and consequent higher melatonin release rate. Entrapment of melatonin in chitosan/Pluronic® F127 microspheres has potentiated chitosan antimicrobial activity against Staphylococcus aureus and five clinical isolates S. aureus MRSA strains. Microspheres were shown to be biocompatible with skin keratinocytes and fibroblasts at concentrations relevant for antimicrobial activity against planktonic bacteria.
authors.affiliation: R&D, PLIVA Croatia Ltd, TEVA Group Member, Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.
authors.forename: Marieta Duvnjak
authors.initials: MD
authors.lastname: Romić
authors.affiliation: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Microbiology, Schrottova 39, 10000 Zagreb, Croatia.
authors.forename: Maja Šegvić
authors.initials: MŠ
authors.lastname: Klarić
authors.affiliation: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Domagojeva 2, 10000 Zagreb, Croatia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Lovrić
authors.affiliation: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Domagojeva 2, 10000 Zagreb, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pepić
authors.affiliation: R&D, PLIVA Croatia Ltd, TEVA Group Member, Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.
authors.forename: Biserka
authors.initials: B
authors.lastname: Cetina-Čižmek
authors.affiliation: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Domagojeva 2, 10000 Zagreb, Croatia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Filipović-Grčić
authors.affiliation: University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Domagojeva 2, 10000 Zagreb, Croatia. Electronic address: ahafner@pharma.hr.
authors.forename: Anita
authors.initials: A
authors.lastname: Hafner
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001458:Bandages; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage* / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D020442:Poloxamer / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D020442:Poloxamer; D048271:Chitosan; D008550:Melatonin
keywords: Chitosan; Melatonin; Microspheres; Pluronic® F127; Wound dressing