Curcumin loaded NLC induces histone hypoacetylation in the CNS after intraperitoneal administration in mice

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 (100 mg/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 (100 mg/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.

Western blot analysis of Ac-H4K12 in the CNS.Figure optionsDownload high-quality image (37 K)Download as PowerPoint slide