title: Development of chitosan oleate ionic micelles loaded with silver sulfadiazine to be associated with platelet lysate for application in wound healing.
abstract: In the treatment of chronic wounds, topical application of anti-infective drugs such as silver sulfadiazine (AgSD) is of primary importance to avoid infections and accelerate wound repair. AgSD is used in burns and chronic wounds for its wide antibacterial spectrum, but presents limitations due to poor solubility and cytotoxicity. In the present work polymeric micelles obtained by self-assembling of chitosan ionically modified by interaction with oleic acid were developed as carriers for AgSD to overcome the drawbacks of the drug. The AgSD loaded micelles were intended to be associated in wound healing with platelet lysate (PL), a hemoderivative rich in growth factors. Unloaded micelles demonstrated good compatibility with both fibroblasts and PL. The relevance of chitosan concentration and of the ratio between chitosan and oleic acid to the drug loading and the particle size of nanoparticles was studied. A marked increase (up to 100 times with respect to saturated solution) of AgSD concentration in micelle dispersion was obtained. Moreover, the encapsulation reduced the cytotoxic effect of the drug towards fibroblasts and the drug incompatibility with PDGF-AB (platelet derived growth factor), chosen as representative of platelet growth factors.
authors.affiliation: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dellera
authors.affiliation: Department of Drug Sciences, University of Pavia, Pavia, Italy. Electronic address: cbonferoni@unipv.it.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Bonferoni
authors.affiliation: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sandri
authors.affiliation: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Ferrari
authors.affiliation: Immunohaematology and Transfusion Service, Apheresis and Cell Therapy Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Del Fante
authors.affiliation: Immunohaematology and Transfusion Service, Apheresis and Cell Therapy Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Perotti
authors.affiliation: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Grisoli
authors.affiliation: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Caramella
mesh_terms: D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000627:therapeutic use; D001792:Blood Platelets / Q000737:chemistry*; D002457:Cell Extracts / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008823:Micelles; D008826:Microbial Sensitivity Tests; D019301:Oleic Acid / Q000737:chemistry*; D010316:Particle Size; D012837:Silver Sulfadiazine / Q000008:administration & dosage* / Q000627:therapeutic use; D013211:Staphylococcus aureus / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000891:Anti-Infective Agents, Local; D002457:Cell Extracts; D004337:Drug Carriers; D008823:Micelles; D019301:Oleic Acid; D048271:Chitosan; D012837:Silver Sulfadiazine
keywords: Chitosan; Oleic acid; Platelet lysate; Polymeric micelles; Silver sulfadiazine; Wound healing