ABSTRACT
We studied different methods of preparing alpha-tocopherol acetate (ATA) nanoparticles, which are to be used in targeting the lungs as aerosols in order to prevent cigarette smoke toxicity. Poly-(lactide) nanoparticles were prepared using nanoprecipitation and solvent evaporation techniques, which produced, respectively, too small and too large nanoparticles to be aerosolized. The emulsification-diffusion method produced 2 months stable nanoparticles with a size between (500-700 nm). Increasing ATA concentration (1-7 mg/mL) induced a decrease in the association rate (97-93%) and in the adsorbed ATA rate (7-4.5%), which was associated with variations of Zeta potentials (-27.5 to -24.3 mV) and decrease in polymeric wall thickness and density.
Subject(s)
Antioxidants/administration & dosage , Antioxidants/chemistry , Drug Delivery Systems , Nanoparticles , alpha-Tocopherol/administration & dosage , alpha-Tocopherol/chemistry , Aerosols/chemistry , Antioxidants/therapeutic use , Diffusion , Drug Compounding/methods , Drug Stability , Emulsions , Lung/metabolism , Nanotechnology/methods , Particle Size , Nicotiana/toxicity , Tobacco Smoke Pollution/prevention & control , alpha-Tocopherol/therapeutic useABSTRACT
New nanoassemblies were instantaneously prepared by mixing two aqueous solutions, one containing a beta-cyclodextrin polymer (pbetaCD), and the other a hydrophobically modified by alkyl chains dextran (MD). The formation mechanism and the inner structure of these nanoassemblies were analysed using surface tension measurements and (1)H NMR spectroscopy. The effect of a hydrophobic guest molecule, such as benzophenone (BZ), on the formation and stability of the nanoassemblies was also evaluated. MD exhibited the typical behaviour of a soluble amphiphilic molecule and adsorbed at the air/water interface. Whereas the injection of native beta-CDs in the solution beneath the adsorbed MD monolayer did not produce any change in the surface tension, that of the pbetaCD resulted in an increase in the surface tension, indicating the desorption of the polymer from the interface. This result accounts for a cooperative effect of beta-CDs linked together in the pbetaCD polymer on dextran desorption. The presence of benzophenone in the system hindered the sequestration of dextran alkyl moieties by beta-CD in the polymer without impeding the formation of associative nanoassemblies of 100-200 nm. (1)H NMR investigations demonstrated that, in the BZ-loaded nanoassemblies, the hydrophobic molecule was mainly located into the cyclodextrin cavities.
Subject(s)
Benzophenones/chemistry , Dextrans/chemistry , Nanoparticles/chemistry , Propylene Glycols/chemistry , beta-Cyclodextrins/chemistry , Hydrophobic and Hydrophilic Interactions , Magnetic Resonance SpectroscopyABSTRACT
Inclusion complexes of nefopam base (NEF) with various beta-cyclodextrins (betaCDs) were investigated. All tested betaCDs increased the apparent solubility of NEF according to a Higuchi AL type plot (except betaCD: AN type plot), which indicates the formation of 1:1 stoichiometry inclusion complexes. 1H-NMR and 13C-NMR experiments showed that complexation by CDs allowed an easy separation of the R and S enantiomers. Based on spectral data obtained from the two-dimensional rotating frame nuclear Overhauser effect spectroscopy (2D-ROESY), a reasonable geometry for the complexes could be proposed implicating the insertion of the benzoxazocine ring into the wide end of the torus cavity.
Subject(s)
Analgesics, Non-Narcotic/administration & dosage , Nefopam/administration & dosage , beta-Cyclodextrins/administration & dosage , Administration, Sublingual , Analgesics, Non-Narcotic/chemistry , Analgesics, Non-Narcotic/pharmacokinetics , Animals , Biological Availability , Humans , In Vitro Techniques , Macromolecular Substances , Models, Molecular , Nefopam/chemistry , Nefopam/pharmacokinetics , Nuclear Magnetic Resonance, Biomolecular , Solubility , Spectroscopy, Fourier Transform Infrared , Stereoisomerism , WaterABSTRACT
Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant disease characterized by cutaneous benign tumors called neurofibromas. Surgery takes an important place in managing these skin disorders. However, skin distensibility and softness of NF1 patients quickly offset the surgical benefit. The aim of this study was to determine the rheological behavior of neurofibromas and compare it with healthy skin in an attempt to comprehend what leads to this phenomenon. Thirty patients were admitted to this study. A group of 24 healthy control subjects was also included. The skin elasticity was assessed by a noninvasive in vivo suction device (Cutometer) including 5 consecutive suctions. The assessments were performed on neurofibroma skin, the supposedly healthy skin around neurofibromas and the healthy skin of control subjects. The extensibility at the first and the fifth traction in NF1 patients (neurofibromas and the supposedly healthy skin around it) was significantly different compared to the healthy skin of control subjects. The viscoelastic parameters obtained from the neurofibromas were significantly different in comparison to those obtained from the supposedly healthy skin of NF1 patients and the healthy skin of control subjects. The rheological profiles of the neurofibromas and the apparent healthy skin of NF1 patients demonstrated a hyperextensibility behavior, but in neurofibromas, the skin was unable to return to its initial position at the end of the stretch.
