CURCUMIN LOADED NLC INDUCES HISTONE HYPOACETYLATION IN THE CNS AFTER INTRAPERITONEAL ADMINISTRATION IN MICE

Curcumin (CUR) is a natural substance widely investigated for its potential therapeutic effect as an anticancer and anti-inflammatory agent. CUR shows an interesting pharmacological activity since is a powerfulp300-specific histone acetyltransferase (HAT) inhibitor. Unfortunately, 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 by ultrasonication method (US) 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).US method, used in this work, gave interesting results: PCS analyses showed that the encapsulation of CUR produced a moderate increase in size (NLC CUR,162.4 ± 10.5 nm) with respect to the empty nanoparticles(NLC, 142.7 ± 11.3 nm). NLC-CUR showed high encapsulation efficiency (87% ± 1.2) related to CUR lipophilic character and high affinity toward the inner oil phase. 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.