title: Curcumin loaded NLC induces histone hypoacetylation in the CNS after intraperitoneal administration in mice.
abstract: The natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin (CUR), has been widely investigated for its potential therapeutic effect as an anticancer and anti-inflammatory agent. Notwithstanding this interesting pharmacological profile, CUR shows some drawbacks, such as poor absorption and a very fast metabolism and elimination, that limit its clinical use. Aim of the present study was to formulate CUR loaded nanostructured lipid carriers (NLC-CUR) in order to improve the bioavailability and stability of this compound after systemic administration with increased effects in the central nervous system (CNS). NLC-CUR were prepared and characterized on their physicochemical properties by PCS and DSC analyses. Thus, NLC-CUR were systemically injected and the effects in the CNS were compared with a CUR control formulation containing 0.05% DMSO (DMSO-CUR). Our results demonstrate that CUR is able to decrease histone acetylation in the CNS when included in NLCs. Western blot analysis shows that intraperitoneal injection of NLC-CUR (100mg/kg) in mice induces a marked hypoacetylation of histone 4 (H4) at lysine 12 (K12) in the spinal cord compared with control group. Notably, DMSO-CUR (100mg/kg) did not change the H4K12 acetylation level in the CNS. Our study suggests a novel approach to ameliorate the pharmacokinetics of CUR that allows a better permeation in the CNS.
authors.affiliation: Department of Drug Sciences, Faculty of Pharmacy, University of Catania, Catania, Italy. capuglia@unict.it
authors.forename: Carmelo
authors.initials: C
authors.lastname: Puglia
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Frasca
authors.forename: Teresa
authors.initials: T
authors.lastname: Musumeci
authors.forename: Luisa
authors.initials: L
authors.lastname: Rizza
authors.forename: Giovanni
authors.initials: G
authors.lastname: Puglisi
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonina
authors.forename: Santina
authors.initials: S
authors.lastname: Chiechio
mesh_terms: D000107:Acetylation; D000818:Animals; D001682:Biological Availability; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors; D006657:Histones / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size
chemical_list: D004337:Drug Carriers; D006657:Histones; D008055:Lipids; D051548:Histone Acetyltransferases; D003474:Curcumin