Preliminary Study of Conformation and Drug Release Mechanism of Doxorubicin-Conjugated Glycol Chitosan, via cis-Aconityl Linkage, by Molecular Modeling

An investigation of the structure and drug release mechanism of a drug delivery system is proposed on the basis of semi-empirical and ab initio computations in vacuum stage. Cis-aconityl linkage is used to improve the interaction between an anti-cancer agent, doxorubicin, and a glycol chitosan biopolymer. It has been found that the doxorubicin-conjugated glycol chitosan carrier has more stability. The stability is increased when the lengths of the polyethylene glycol (PEG) chains in the glycol chitosan biopolymer are increased. Cis-aconityl can release doxorubicin under appropriate environmental conditions. Relative energies of this mechanism in an acid condition, as determined by B3LYP/6-31G//PM3, are 122.41, 119.27, 160.18 and 222.22 kcal/mol, and by the B3LYP/6-31G//HF/6-31G method are 54.23, 109.28, 219.98 and 980.49 kcal/mol, with mono-, di-, tri-, and quanta-ethylene glycol, respectively. In a normal condition, the relative energies are above 300 kcal/mol for all reactions. Therefore, cis-aconityl will release doxorubicin in an acid solution but not in a normal condition. The glycol chitosan polymer can be degraded in an acid solution as well. Long PEG chains influence the release mechanism of doxorubicin. The proposed length of the PEG chain is di-ethylene glycol. These simulation results agree well with various reported experimental data.     

Simulation of mass exchange networks using modified genetic algorithms

The optimum water usage network leads to both a minimum of freshwater consumption and a minimum of generated wastewater. This work is to develop a mass-exchange networks (MENs) module for a minimum freshwater usage target. This module works as an interface to retrieve supplemental data of chemical processes from a process simulator and to communicate this to the genetic algorithm optimizer. A reuse system and a regeneration/recyclingsystem with a single contaminant are considered as approaches for freshwater minimization. In the formulated model, as mixed integer nonlinear programming (MINLP), all of the variables are divided into independent and dependent variables. The values of independent variables come from randomization, whereas the values of dependent variables come from simultaneous solutions of a set of equality constraints after assigning the values of independent variables. This method is applied to the steps of initialization, crossover and mutation. The MENs module is validated with a tricresylphosphate process consisting of five unit operations. Water is used to remove a fixed content of cresol. From the result, the module gives a reliable solution for freshwater minimization, which can satisfy mass balance and constraints. The results show that reuse and regeneration/recycling strategies can reduce freshwater consumption, including wastewater generated. Reuse cannot decrease the mass load of the contaminant, while regeneration/recycling can. In addition, regeneration requires less freshwater than the reuse process.     

Production of theophylline and polyethylene glycol 4000 composites using Gas Anti-Solvent (GAS) process

Production of drug composites can be used to enhance the dissolution rate of poorly-water soluble drugs. In this research, Gas Anti-Solvent (GAS) technique was applied to produce composites between theophylline (THEO) and polyethylene glycol (PEG) by using dense carbon dioxide as an anti-solvent. It was found that the size of the composites decreased as the concentration of PEG 4000 decreased. However, when increasing the temperature the degree of aggregation and particles size were increased. It was also found that a decrease in ethanol amount in the solvent mixture of dichloromethane and ethanol resulted in a decrease of particle size. The theophylline-PEG composites with the highest drug loading of 16.70% were obtained when using the mass ratio of drug and polymer at 2:3 wt.% in the dichloromethane and ethanol solvent of 50:50%v/v and 25 °C. The dissolution rate of the prepared composites in phosphate buffered solution was found to be 20.8 times greater than that of the original material.     

Xylitol production by liquid emulsion membrane encapsulated yeast cells

BACKGROUND: Liquid emulsion membrane (LEM)‐encapsulated live cells can be used to produce various products. This work reports on LEM‐encapsulated cells for producing xylitol and models the production process. RESULTS: Encapsulated cells of Candida mogii ATCC 18364 were used to produce xylitol from xylose. Soybean oil LEM consisting of 5% (w/v) lanolin and microwaxes was found most suitable for this process. The LEM‐encapsulated cells were immobilized in a tubular biocatalytic loop. Xylitol was produced under oxygen‐limited and aerobic conditions. Xylitol productivity and yield were 0.005 g L^?1 h^?1 and 0.52 g g^?1, respectively, for oxygen‐limited operation. Under aerobic conditions, xylitol productivity increased greatly to 0.022 g L^?1 h^?1, but yield on xylose declined to 0.49 g g^?1. A mathematical model successfully described substrate consumption and product formation in the LEM‐immobilized cell system. CONCLUSION: Potentially, immobilized cell LEM systems are useful for certain fermentations and they can be successfully modeled, as shown by the example of xylitol from xylose process. Copyright © 2009 Society of Chemical Industry     

Kinetic of myristic acid esterification with methanol in the presence of triglycerides over sulfated zirconia

The esterification of myristic acid with methanol in presence of triglycerides using sulfated zirconia prepared by solvent-free method as the heterogeneous catalyst was studied. The effects of reaction temperature (393–443 K), catalyst loading (1–3 %wt) and molar ratio of oil to methanol (1:4–1:20) on the conversion of myristic acid were investigated. The experimental data was interpreted with a second order pseudo-homogeneous kinetic model. The kinetic parameters were obtained. A good agreement between the experimental data and the model was observed. Sulfated zirconia prepared by solvent-free method exhibited high catalytic activity for this reaction. Low activation energy of 22.51 kJ mol^?1 was obtained in the range of temperature of 393–443 K.     

Simultaneous Conversion of Triglyceride/Free Fatty Acid Mixtures into Biodiesel Using Sulfated Zirconia

Simultaneous transesterification and esterification of rapeseed oil with methanol in the presence of myristic acid was investigated. The effect of reaction temperature (120, 150 and 170 °C) and the effect of initial free fatty acid content in oil (0, 10 and 20 wt%) on reaction rate were studied. The catalysts were found to increase the rate of all reactions. Sulfated zirconia prepared by a solvent-free method exhibited higher activity in simultaneous reaction than the conventional method. The presence of 10 wt% free fatty acids in the triglyceride increased the reaction rate and the final total fatty acid methyl esters content, and suggests that a “non-catalytic” reaction may be feasible.     

Application of gas anti-solvent process to the recovery of andrographolide from <Emphasis Type="Italic">Andrographis paniculatanees</Emphasis>

The gas anti-solvent (GAS) process was employed to extract andrographolide, which is the active ingredient found in Andrographis Paniculatanees, using carbon dioxide as an anti-solvent. The effects of temperature, flow rate and solvent type on the extraction recovery, particle size and morphology were investigated in this study. The experiments were conducted at the temperature ranging from 25–45 °C, carbon dioxide flow rate of 1–15 mL/min, and various types of organic solvents (methanol, ethanol, acetone and N,N-dimethylformamide). The extracted product was analyzed using high performance liquid chromatography (HPLC). The highest extraction yield was found to be 1.24 g andrographolide per 100 g of A. paniculata when using acetone as a solvent, carbon dioxide flow rate of 5 mL/min and the temperature of 35 °C. It was also found that no significant change in size or morphology of the precipitates was observed when changing temperature, carbon dioxide flow rate and solvents.     

Simulation of Doxorubicin Delivery via Glucosamine(ethylene glycol) Carrier

This article focuses on the molecular modeling of the release of doxorubicin from capsules composed of glucosamine(ethylene glycol) oligomers. Doxorubicin forms micelle structures with glucosamine(ethylene glycol), and the drug release mechanism can be studied through the modeling of oligomeric bond breaking under acidic, neutral, or basic conditions. Under these conditions, the activation energies were calculated to be 145.51, 135.78, and 287.60 kcal/mol, respectively, at the B3LYP/6-31G//PM3 level. Based on these values, doxorubicin can be released into acidic and neutral solutions but not into basic solution. Ethylene glycol chain length in glucosamine(ethylene glycol) also effects drug release. As the length of ethylene glycol increases, the amount of drug released increases under acidic conditions, but decreases under neutral and basic conditions. When the drug is released from glucosamine(ethylene glycol) oligomers, the drug molecule and glucosamine(ethylene glycol) molecules form a micelle structure. Studies found that, as the length of the ethylene glycol chains increases, the micelle structure is more easily formed. The ethylene glycol group can deliver doxorubicin to cancer cells in micelle form.