Incorporation methods for cholic acid chitosan-g-mPEG self-assembly micellar system containing camptothecin

A water-insoluble anticancer agent, camptothecin (CPT) was incorporated to a polymeric micelle carrier system preparing from cholic acid chitosan-grafted poly (ethylene glycol) methyl ether (CS-mPEG-CA). CS-mPEG-CA formed a core–shell micellar structure with a critical micelle concentration (CMC) of 7.08 μg/ml. Incorporation efficiency was investigated by varying physical incorporation method and initial drug loading. Among three incorporation methods (dialysis, emulsion and evaporation methods), an emulsion method showed the highest CPT incorporation efficiency. Increasing the initial CPT loading from 5 to 40%, the incorporation efficiency decreased. In all examined CPT-loaded CS-mPEG-CA micelles, 5% initial drug loading showed the highest drug incorporation efficiency. Release of CPT from the micelles was sustained when increasing the initial CPT loading. This indicates the importance of incorporation method and the initial drug loading to obtain the optimum particle size with high drug loading and sustained drug release. When compared to the unprotected CPT, CPT-loaded CS-mPEG-CA micelles were able to prevent the hydrolysis of the lactone group of the drug. This novel CS-mPEG-CA polymer presents considerable potential interest in the further development of CPT carrier.     

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.     

Optimization of size and shape of composite heat sinks with phase change materials

A composite heat sink is one in which a phase change material is interspersed with a high thermal conductivity base material to maximize the thermal performance of the device. Unlike constant area fins considered in literature, this work considers a repeating elemental composite heat sink (ECHS) with variable area fins. The base material is aluminium and the phase change material is n-Eicosane. An in house code was developed in MATLAB© to determine the time of operation for a vertical fins ECHS for a one dimensional approximation. This was followed by a two dimensional analysis of the problem using FLUENT 6.3. The effects of the shape of the interface surface on the time of operation and overall heat dissipated are determined and design modifications for the composite Heat Sinks based on the results obtained are suggested.     

Preparation of PMMA/acid-modified chitosan core-shell nanoparticles and their potential as gene carriers

The core-shell nanoparticles consisting of poly(methyl methacrylate) (PMMA) cores surrounded by various acid-modified chitosan shells were synthesized using a surfactant-free emulsion copolymerization, induced by a tert-butylhydroperoxide (TBHP) solution. Methyl methacrylate (MMA) was grafted onto four acid-modified chitosans (hydrochloric, lactic, aspartic, and glutamic acids) with MMA conversions up to 64%. The prepared nanoparticles had diameter ranging from 100 to 300 nm characterized by atomic force microscopy and displayed highly positive surface charges up to +77 mV. Transmission electron microscopic images clearly revealed well-defined core-shell morphology of the nanoparticles where PMMA cores were coated with acid-modified chitosan shells. The effect of acid-modified chitosans on particle size, intensity of surface charge, morphology, and thermal stability were determined systematically. The plasmid DNA/nanoparticles complexes were investigated with ζ-potential measurement. The results suggested that these nanoparticles can effectively complex with plasmid DNAs via electrostatic interaction and could be used as gene carriers.

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.