pH-responsive nanostructures based on surface active fatty acid-protic ionic liquids for imiquimod delivery in skin cancer topical therapy

or topical treatment of skin cancer, the design of pH-responsive nanocarriers able to selectively release the drug in the tumor acidic microenvironment represents a reliable option for targeted delivery. In this context, a series of newly synthesized surface-active fatty acid-protic ionic liquids (FA-PILs), based on tetramethylguanidinium cation and different natural hydrophobic fatty acid carboxylates, have been investigated with the aim of developing a pH-sensitive nanostructured drug delivery system for cutaneous administration in the skin cancer therapy. The capability of FA-PILs to arrange in micelles when combined with each other and with the non-ionic surfactant d-α-Tocopherol polyethylene glycol succinate (vitamin E TPGS) as well as their ability to solubilize imiquimod, an immuno-stimulant drug used for the treatment of skin cancerous lesions, have been demonstrated. The FA-PILs-TPGS mixed micelles showed pH-sensitivity, suggesting that the acidic environment of cancer cells can trigger nanostructures’ swelling and collapse with consequent rapid release of imiquimod and drug cytotoxic potential enhancement. The in vitro permeation/penetration study showed that the micellar formulation produced effective imiquimod concentrations into the skin exposed to acid environment, representing a potential efficacious and selective drug delivery system able to trigger the drug release in the tumor tissues, at lower and less irritating drug concentrations. © 2020 by the author

Stage-variations of anandamide hydrolase activity in the mouse uterus during the natural oestrus cycle

Recent studies have demonstrated that the endogenous cannabinoids are important modulators of fertility in mammals. In particular, a role of the endocannabinoid system in early stages of embryo development, oviductal transport of embryos, pregnancy maintenance and labour has been demonstrated in rodents and/or in humans. In the present paper, we report the analysis of FAAH activity and protein content in the mouse uterus as a function of the natural oestrus cycle stages. Variations of FAAH activity are discussed in relationship to changes in sex steroid levels and to the possible action of AEA on remodelling of uterine tissues

Influence of alkene structure on the stability of alkene-Br(2) complexes: Effect of chlorine substitution

The reaction of chloro substituted ethylenes with Br(2) stops at the stage of charge transfer complexes. These complexes were studied spectrophotometrically in the UV-vis region. DFT and ab initio calculations (B3LYP and MP2 levels) were carried out in order to clarify the structures and establish the factors affecting the stability of this kind of complex. The complexes are characterized by a T shape structure with a Br-Br unit lying perpendicular to the C-C double bond. B3LYP calculations show a trend in the stabilization energies which fits well with the experimental results. At variance MP2 calculations overestimate the correlation energies of the bromine complexes with trichloroethylene and tetrachloroethylene. The stability of these elusive complexes is mainly influenced by the charge transfer contribution and by a destabilizing effect arising from bromine-chlorine interaction. The geometry and the relative stability of the corresponding ionic intermediates (bromiranium or beta-bromocarbenium ions), which have been detected neither by UV nor NMR measurements, were also evaluated through B3LYP calculations

The first intermediates in the bromination of bicyclo[3.3.1]nonylidenebicyclo[3.3.1]nonane, combination of experiments and theoretical results RID E-4986-2010 RID A-2996-2011

Bicyclo[3.3.1] nonylidenebicyclo[ 3.3.1] nonane ( 1) and adamantylideneadamantane (Ad = Ad) are two caged olefins with closely related structures at the double bond. Both compounds react instantaneously with Br(2) in chlorinated hydrocarbon solvents to give mixtures of olefin - Br(2) aggregates identified as the 1: 1 pi-complex and bromonium tribromide, bromonium pentabromide ion pairs. The stoichiometry, formation constants and the electronic spectra of all the species present at equilibrium (pi-complex and bromonium ions), obtained by addition of bromine to alkene 1, have been determined in 1,2-dichloroethane at 25 degrees C and compared with the values that characterize the corresponding aggregates arising from Ad = Ad. The absence of the two bridging CH(2) groups in 1 significantly affects all the formation constants. Moreover, at variance with Ad=Ad, olefin 1 reacts with bromine to give, depending on reagent concentration, a substitution product. DFT (B3LYP) and ONIOM computations of 1: 1 Br(2) - olefin complexes for 1 and Ad = Ad confirm that the association energy is larger for the complex 1 - Br(2). The higher stability of this species seems to be correlated to the greater IP of 1 with respect to Ad = Ad which is able to compensate the reduced polarizability. The experimental value of the formation constant found for the complex 1 - Br(2), 643 vs 289 M(-1) further supports the primary role exerted by dispersion interactions in alkene-Br(2) pi-complexes