Computational simulation on the study of Tacrolimus and its improved dermal retention using Poly(Ԑ-caprolactone) nanocapsules.

Tacrolimus (TAC) is a drug from natural origin that can be used for topical application to control autoimmune skin diseases such as atopic dermatitis, psoriasis, and vitiligo. Computational simulation based on quantum mechanics theory by solving Schrödinger Equation for n-body problem may allow the theoretical calculation of drug geometry, charge distribution and dipole moment, electronic levels and molecular orbitals, electronic transitions, and vibrational transitions. Additionally, the development of novel nanotechnology-based delivery systems containing TAC can be an approach for reducing the dose applied topically, increasing dermal retention, and reducing the reported side effects due to the controlled release pattern. Firstly, this paper was devoted to obtaining the molecular, electronic, and vibrational data for TAC by using five semi-empirical (SE) methods and one Density Functional Theory (DFT) method in order to expand the knowledge about the drug properties by computational simulation. Then, this study was carried out to prepare TAC-loaded poly(ԑ-caprolactone) nanocapsules by interfacial polymer deposition following solvent displacement and investigate the in vitro drug permeation using the Franz diffusion cell and the photoacoustic spectroscopy. Computational simulations were compared in the three schemes SE/SE, SE/DFT, and DFT/DFT, where the first method represented the procedure used for geometry optimization and the second one was performed to extract electronic and vibrational properties. Computational data showed correspondence with TAC geometry description and electronic properties, with few differences in HOMO - LUMO gap (Δ) and dipole values. The SE/DFT and DFT/DFT methods presented a better drug description for the UV-Vis, Infrared, and Raman spectra with low deviation from experimental values. Franz cell model demonstrated that TAC was more delivered across the Strat-M® membrane from the solution than the drug-loaded poly(ԑ-caprolactone) nanocapsules. Photoacoustic spectroscopy assay revealed that these nanocapsules remained more retained into the Strat-M® membranes, which is desirable for the topical application.

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis.

BACKGROUND: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. METHODS: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. RESULTS: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (-38 to -42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer-Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug. CONCLUSIONS: TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.

Functioned catalysts with magnetic core applied in ibuprofen degradation.

In the present work, the performance of Ag/ZnO/CoFe2O4 magnetic photocatalysts in the photocatalytic degradation of ibuprofen (IBP) was evaluated. This study considered the use of pure Ag/ZnO (5% Ag) and also the use of the Ag/ZnO/CoFe2O4 magnetic catalysts containing different amounts (5, 10 and 15% wt) of cobalt ferrite (CoFe2O4). The catalysts were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and photoacoustic spectroscopy. To carry out the photocatalytic degradation reaction, different concentrations of the ibuprofen contaminant solution (10, 20 and 30 ppm) and different concentrations of photocatalyst were tested (0.3 g L-1, 0.5 g L-1 and 1.0 g L-1). The reaction parameters studied were: IBP concentration, catalyst concentration, adsorption and photolysis, influence of the matrix, radiation source (solar and artificial) and the effect of organic additive. At the end of the photocatalytic tests, the best operating conditions were defined. Considering the obtained results of degradation efficiency and magnetic separation, the optimal parameters selected to proceed with the other tests of the study were: ibuprofen solution concentration 10 ppm, Ag/ZnO/CoFe2O4 (5%) catalyst at a concentration of 0.3 g L-1 and pH 4.5 of the reaction medium. The results indicated the feasibility of magnetic separation of the synthesized catalysts. A long duration test indicated that the catalyst exhibits stability throughout the degradation reaction, as more than 80% of IBP was degraded after 300 minutes. The photocatalytic activity was directly affected by the ferrite load. The higher the nominal load of ferrite, the lower the performance in IBP degradation. It was also observed that the smallest amount of ferrite studied was enough for the catalyst to be recovered and reused. The adsorption and photolysis tests did not show significant results in the IBP degradation. In addition, it was possible to verify that the aqueous matrix, the use of solar radiation and the addition of additive (acid formic) were interfered directly in the process. The catalyst reuse tests indicated that it can be recovered and reused at least three times without considerable catalytic activity loss.

Adapalene-loaded poly(ε-caprolactone) microparticles: Physicochemical characterization and in vitro penetration by photoacoustic spectroscopy.

Adapalene (ADAP) is an important drug widely used in the topical treatment of acne. It is a third-generation retinoid and provides keratolytic, anti-inflammatory, and antiseborrhoic action. However, some topical adverse effects such as erythema, dryness, and scaling have been reported with its commercial formula. In this sense, the microencapsulation of this drug using polyesters can circumvent its topical side effects and can lead to the enhancement of drug delivery into sebaceous glands. The goal of this work was to obtain ADAP-loaded poly(ε-caprolactone) (PCL) microparticles prepared by a simple emulsion/solvent evaporation method. Formulations containing 10 and 20% of ADAP were successfully obtained and characterized by morphological, spectroscopic, and thermal studies. Microparticles presented encapsulation efficiency of ADAP above 98% and showed a smooth surface and spherical shape. Fourier transform infrared spectroscopy (FTIR) results presented no drug-polymer chemical bond, and a differential scanning calorimetry (DSC) technique showed a partial amorphization of the drug. ADAP permeation in the Strat-M membrane for transdermal diffusion testing was evaluated by photoacoustic spectroscopy (PAS) in the spectral region between 225 and 400 nm after 15 min and 3 h from the application of ADAP-loaded PCL formulations. PAS was successfully used for investigating the penetration of polymeric microparticles. In addition, microencapsulation decreased the in vitro transmembrane diffusion of ADAP.

Thermal characterization in vitro of human nail: photoacoustic study of the aging process.

In the present work, the rear photoacoustic signal technique is used to determine thermal properties of human nails. The aging process of the human nail is analyzed through its thermal diffusivity and specific heat and using these results, thermal conductivity and thermal effusivity is determined. The study in vitro of this natural polymer showed a minimum for thermal properties to age about 20 years and an increase and possible saturation of them for ages over 50 years. The minimum value found for thermal diffusivity was close to 10x10(-4) cm2 s(-1) with saturation near 18x10(-4) cm2 s(-1). Thermal conductivity and effusivity presents the same behavior.