Enhancement of cyclosporine aqueous solubility using α- and hydroxypropyl β-cyclodextrin mixtures

Cyclodextrins (CDs) are cyclic oligosaccharides that form inclusion complexes with lipophilic molecules through their hydrophobic central cavity. In this study, the effect of α-CD, hydroxylpropyl-β-CD (HP-β-CD) and mixtures of these two CDs on the aqueous solubility of cyclosporine A (CyA) was investigated. Infrared spectroscopy and thermal analysis were used to confirm CyA-CD complex formation. CyA aqueous solubility was increased by 10 and 80 fold in the presence of α-CD and HP β-CD, respectively. The phase-solubility profile for HP-β-CD was linear while that for α-CD had positive deviation from linearity. In the presence of constant concentration of α-CD (15% w/v), aqueous solubility of CyA was further increased upon addition of HP-β-CD up to a concentration of 20% w/v. At higher HP-β-CD concentrations, aqueous solubility of CyA was observed to decrease. Addition of sodium acetate (up to 5% w/v) to aqueous solutions containing 20% w/v HP-β-CD and increasing concentrations of α-CD resulted in a significant reduction in CyA solubility. Complex formation between CyA and both α-CD and HP-β-CD was confirmed by differential scanning calorimetry (DSC). No significant changes were observed in the IR spectra of either CyA or CD following complex formation suggesting chemical interaction between CyA and the CD was unlikely. Phase-solubility studies showed that α-CD had a much greater effect on the solubility of CyA than HP-β-CD. Addition of HP-β-CD to aqueous solutions of α-CD affected the solubility of CyA in these systems. A mixture of 15% w/v α-CD and 20% w/v HP-β-CD was optimal for increasing aqueous solubility of CyA.     

Raman active jagged-shaped gold-coated magnetic particles as a novel multimodal nanoprobe

The creation of novel engineered multimodal nanoparticles (NPs) is a key focus in bionanotechnology and can lead to deep understanding of biological processes at the molecular level. Here, we present a multi-component system made of gold-coupled core-shell SPIONs, as a new nanoprobe with signal enhancement in surface Raman spectroscopy, due to its jagged-shaped gold shell coating.     

First principles versus artificial neural network modelling of a solar desalination system with experimental validation

ABSTRACT

The present study mainly focuses on enhancing the performance of solar still unit using solar energy through cylindrical parabolic collector and solar panels. A 300 W solar panel is used to heat saline water by thermal elements outside the solar still unit. Solar panels are cooled during the hot hours of the day; thus, reducing their temperature may lead to an increase in solar panel efficiency followed by an increase in the efficiency of the solar still unit. The maximum amount of freshwater used in the experiment was 2.132 kg/day. The experiments were modelled using ANNs. Based on neural network simulation results, there is a significant correlation between experimental data and neural network modelling. This paper compares experimental data with data obtained from mathematical modelling and ANNs. As a conclusion, the artificial neural network prediction has been more accurate than the simplified first principles model presented.     

The effect of cyclodextrin mixtures on aqueous solubility of beclomethasone dipropionate

The aim of present study was to evaluate the effect of natural, synthetic cyclodextrins (CDs) and CD mixtures on aqueous solubility of beclomethasone dipropionate (BDP). The phase solubility studies were done in the presence of 6 CDs. Furthermore, aqueous solubility of BDP was tested in the presence of CD mixtures. The solubility of BDP in water was increased by 30, 77, 155 and 30 folds in the solution containing 20%?w/v α-CD, hydroxylpropyl β-CD (HP-β-CD), hydroxypropyl γ-CD (HP-γ-CD) and sulphobutylether β-CD (SBE-β-CD), respectively. CD mixtures had remarkable effect on the aqueous solubility of BDP so that solubility in water increased between 200 and 1,500 times in the presence of different CD mixtures. Further addition of sodium acetate to the solubilisation medium reduced the aqueous solubility. In conclusion, CD complexation was able to improve the aqueous solubility of BDP. The synergistic effect of cyclodextrin mixture was observed.     

Transmission line model for extraction of transmission characteristics in photonic crystal waveguides with stubs: optical filter design

A simple and efficient transmission line model is proposed here to study how the transmission characteristics of photonic crystal waveguides are tailored by introduction of stubs patterned in the photonic crystal lattice. It is shown that band-pass and band-stop optical filters can be easily designed and optimized when stubs of appropriate length are brought in. Since the lengths of the designed stubs are not necessarily integer multiples of the photonic crystal lattice constant, a geometric shift in a portion of the photonic crystal structure is shown to be essential. The proposed model is verified by using a rigorous numerical method. An excellent agreement is observed between the numerical results and the transmission characteristics as extracted by the proposed model.     

The enhancement of immunosuppressive effects of cyclosporine A on human T-cells using fusogenic liposomes

The aim of this study was to prepare and characterize neutral, positively charged, negatively charged and fusogenic liposomes of different sizes that contain cyclosporine A (CyA) and to evaluate their immunosuppressive activity on human T-cells. Neutral liposomes containing CyA were prepared from dipalmitoylphosphatidylcholine (DPPC) and cholesterol using the solvent evaporation method. To prepare positively charged, negatively charged and fusogenic liposomes containing CyA; stearylamine (SA), dicetylphosphate (DCP) and dioleoylphosphatidylethanolamine (DOPE) were added to the neutral liposome formulation, respectively. To reduce the size of liposomes containing CyA, extrusion through polycarbonate filters (1000, 400 and 100 nm) was used. The liposomes were characterized by their size, zeta potential and encapsulation efficiency. The in vitro immunosuppressive effects of an aqueous solution of CyA and different liposomes containing CyA were determined on human T-cells by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. The mean diameter of the various multilamellar vesicle (MLV) liposomes containing CyA was between 1.76 and 2.49 μm. The encapsulation efficiency for the different MLV and extruded liposomes containing CyA ranged from 73% to 90%. In vitro immunosuppressive evaluation by T-cell culture showed that fusogenic liposomes have the best inhibitory effects on T-cell proliferation compared to the other liposomes. Reducing the size of the liposomes did not affect the in vitro immunosuppressive activity. The average IC₅₀ for the aqueous solution of CyA and the neutral, positively charged, negatively charged and fusogenic liposomes containing CyA was 4.98 × 10⁻², 7.38, 1.43, 3.84 × 10⁻³ and 7.93 × 10⁻⁵ mM, respectively. The results of this study indicate that fusogenic liposomes have the strongest immunosuppressive activity and could be considered as a suitable delivery system for CyA.     

Quantitative LC Analysis of Cyclosporine A in Ocular Samples

An isocratic reversed-phase HPLC method with ultraviolet detection at 205 nm has been developed for analysis of cyclosporine A (CyA) in rabbit ocular samples. Neither internal standard nor extraction was needed for sample preparation. Acetonitrile (ACN; 1 mL) was added to 250 μL aqueous and vitreous samples to precipitate proteins. The supernatant was dried and the residue was reconstituted in mobile phase and injected for HPLC analysis. Chromatography was performed on an octadecyl silane-A (ODSA) C₁₈ (4.6 × 250 mm, 5 μm) column. The column temperature was fixed at 70 °C and the mobile phase was ACN 65%, methanol 20% and water 15% at a flow rate of 1.5 mL min^?1. The calibration curve for CyA in rabbit ocular samples was linear over the concentration range 0.2 and 10 μg mL^?1 with a correlation coefficient of 0.9992. Intra-day and inter-day precision were 4.61–7.83% and 5.27–10.70%, respectively. Intra-day and inter-day accuracy were 89.2–108% and 83.4–111%, respectively. The limits of detection (LOD) and quantification (LOQ) were 5.7 and 38 ng mL^?1, respectively. The method was successfully used for analysis of CyA in real aqueous and vitreous humor samples from New Zealand albino rabbits. The method is therefore suitable for analysis of CyA in ocular samples.