title: Development of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.
abstract: The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC), is an innovative non- radical scavenger used with success in numerous disease models such as inflammation, neurological disorders, hepatitis and diabetes. The pharmacological treatments have been performed by the intraperitoneal route of administration, representing to date, the main limit for the drug use. The aim of this study was to develop a delivery system that allows the oral administration of IAC while maintaining its therapeutic efficacy. Solid Lipid Microparticles (SLMs) containing a theoretical 18% (w/w) of IAC have been produced by the spray congealing technology; three formulations have been tested (A, B and C) using different low melting point carriers (stearic acid, Compritol(®) HD5ATO and carnauba wax) alone or in combination. All IAC loaded SLMs exhibited a spherical shape, encapsulation efficiency higher than 94% and particle size suitable for the oral route. Administered per os at different dosages in an inflammation rat model, all SLMs demonstrated their efficacy in reducing oedema and alleviating pain, compared to the gold standards Indomethacin and Paracetamol. These results suggested that the SLMs are an efficacious delivery system for the oral administration of IAC, potentially useful for the treatment of others diseases related to an over production of free radicals.
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127, Italy. Electronic address: nadia.passerini@unibo.it.
authors.forename: Nadia
authors.initials: N
authors.lastname: Passerini
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Albertini
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127, Italy.
authors.forename: Marcello Di
authors.initials: MD
authors.lastname: Sabatino
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corace
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Luppi
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via Irnerio 48, 40127, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Canistro
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via Irnerio 48, 40127, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Vivarelli
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via Irnerio 48, 40127, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cirillo
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via Irnerio 48, 40127, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Soleti
authors.affiliation: Medestea Research, via Cernaia 31, 10121, Torino, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Merizzi
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via Irnerio 48, 40127, Italy.
authors.forename: Moreno
authors.initials: M
authors.lastname: Paolini
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D010316:Particle Size; D010880:Piperidines / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D013229:Stearic Acids / Q000008:administration & dosage / Q000737:chemistry; D014885:Waxes / Q000737:chemistry
chemical_list: D016166:Free Radical Scavengers; D008081:Liposomes; D010880:Piperidines; D013229:Stearic Acids; D014885:Waxes; C526136:bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate; C477262:compritol HD5 ATO; D000082:Acetaminophen; D011092:Polyethylene Glycols; C031183:stearic acid; D005990:Glycerol; C026344:carnauba wax; D007213:Indomethacin
keywords: Iac; Inflammation; Oedema; Oral administration; Pain; Radical scavenger; Solid lipid microparticles; Spray congealing