Camptothecin-incorporating N-phthaloylchitosan-g-mPEG self-assembly micellar system: effect of degree of deacetylation

Amphiphilic grafted copolymers, N-phthaloylchitosan-grafted poly (ethylene glycol) methyl ether (PLC-g-mPEG), were synthesized from chitosan with different degree of deacetylation (DD=80%, 85%, 90% and 95%). Due to their amphiphilic characteristic, these copolymers could form micelle-like nanoparticles. The critical micelle concentration (CMC) of these nanoparticles with different DD in water was similar (28microg/ml). Under transmission electron microscope (TEM), the nanoparticles exhibited a regular spherical shape with core-shell structure. The particle sizes determined by dynamic light scattering were in the range of 100-250nm, and increased as the %DD of chitosan increased. The cytotoxicity of phthaloylchitosans (PLC) and PLC-g-mPEG in Hela cells line were evaluated. The results showed that cytotoxicity of PLC and PLC-g-mPEG increased with increasing %DD of chitosan. The cytotoxicity of PLC-g-mPEG was significantly lower than that of PLC. Camptothecin as a model drug was loaded into the inner core of the micelles by dialysis method. It was found that %DD of chitosan, corresponding to the N-phthaloyl groups in the inner core of the nanoparticle obtained, was a key factor in controlling %yield, stability of the drug-loaded micelles, and drug release behavior. As the %DD increased, the CPT-loaded micelles stability increased. Release of CPT from the micelles was dependent on the %DD and a sustained release was obtained in high %DD.     

Microscale chemistry-based design of eco-friendly, reagent-saving and efficient pharmaceutical analysis: a miniaturized Volhard's titration for the assay of sodium chloride

This work demonstrates the extended application of microscale chemistry which has been used in the educational discipline to the real analytical purposes. Using Volhard's titration for the determination of sodium chloride as a paradigm, the reaction was downscaled to less than 2 mL conducted in commercially available microcentrifuge tubes and using micropipettes for the measurement and transfer of reagents. The equivalence point was determined spectrophotometrically on the microplates which quickened the multi-sample measurements. After the validation and evaluation with bulk and dosage forms, the downsized method showed good accuracy comparable to the British Pharmacopeial macroscale method and gave satisfactory precision (intra-day, inter-day, inter-analyst and inter-equipment) with the relative standard deviation of less than 0.5%. Interestingly, the amount of nitric acid, silver nitrate, ferric alum and ammonium thiocyanate consumed in the miniaturized titration was reduced by the factors of 25, 50, 50 and 215 times, respectively. The use of environmentally dangerous dibutyl phthalate was absolutely eliminated in the proposed method. Furthermore, the release of solid waste silver chloride was drastically reduced by about 25 folds. Therefore, microscale chemistry is an attractive, facile and powerful green strategy for the development of eco-friendly, safe, and cost-effective analytical methods suitable for a sustainable environment.     

Ninhydrin reaction on thiol-reactive solid and its potential for the quantitation of d-penicillamine

While aminothiols produce weak purple-colored reactions with ninhydrin, we demonstrate for the first time that this color could be intensely developed. Using a d-penicillamine paradigm, adsorption of this compound via a disulfide bond onto thiol-reactive solid prior to ninhydrin reaction allowed spectrophotometrical monitoring of the supernatant at 570 nm. Compared with off-solid method, this approach expanded the linear concentration range to 50-600 μg mL⁻¹ and enhanced the sensitivity so that d-penicillamine with the concentrations of less than 100 μg mL⁻¹ could be accurately quantitated by using a second-order polynomial calibration curve. Additionally, this assay was unaffected by disulfide adduct interference, highlighting its potential for the analysis of d-penicillamine as well as other aminothiols.     

Multivariate Multiscale Cosine Similarity Entropy and Its Application to Examine Circularity Properties in Division Algebras

The extension of sample entropy methodologies to multivariate signals has received considerable attention, with traditional univariate entropy methods, such as sample entropy (SampEn) and fuzzy entropy (FuzzyEn), introduced to measure the complexity of chaotic systems in terms of irregularity and randomness. The corresponding multivariate methods, multivariate multiscale sample entropy (MMSE) and multivariate multiscale fuzzy entropy (MMFE), were developed to explore the structural richness within signals at high scales. However, the requirement of high scale limits the selection of embedding dimension and thus, the performance is unavoidably restricted by the trade-off between the data size and the required high scale. More importantly, the scale of interest in different situations is varying, yet little is known about the optimal setting of the scale range in MMSE and MMFE. To this end, we extend the univariate cosine similarity entropy (CSE) method to the multivariate case, and show that the resulting multivariate multiscale cosine similarity entropy (MMCSE) is capable of quantifying structural complexity through the degree of self-correlation within signals. The proposed approach relaxes the prohibitive constraints between the embedding dimension and data length, and aims to quantify the structural complexity based on the degree of self-correlation at low scales. The proposed MMCSE is applied to the examination of the complex and quaternion circularity properties of signals with varying correlation behaviors, and simulations show the MMCSE outperforming the standard methods, MMSE and MMFE.