Prediction of Partition Coefficients in SDS Micelles by DFT Calculations

A computational methodology using Density-Functional Theory (DFT) calculations was developed to determine the partition coefficient of a compound in a solution of Sodium Dodecyl Sulfate (SDS) micelles. Different sets of DFT calculations were used to predict the free energy of a set of 63 molecules in 15 different solvents with the purpose of identifying the solvents with similar physicochemical characteristics to the studied micelles. Experimental partition coefficients were obtained from Micellar Electrokinetic Chromatography (MEKC) measurements. The experimental partition coefficient of these molecules was compared with the predicted partition coefficient in heptane/water, cyclohexane/water, N-dodecane/water, pyridine/water, acetic acid/water, decan-1-ol/water, octanol/water, propan-2-ol/water, acetone/water, propan-1-ol/water, methanol/water, 1,2-ethane diol/water, dimethyl sulfoxide/water, formic acid/water, and diethyl sulphide/water systems. It is observed that the combination of pronan-1-ol/water solvent was the most appropriated to estimate the partition coefficient for SDS micelles. This approach allowed us to estimate the partition coefficient orders of magnitude faster than the classical molecular dynamics simulations. The DFT calculations were carried out with the well-known exchange correlation functional B3LYP and with the global hybrid functional M06-2X from the Minnesota functionals with 6-31++G ** basis set. The effect of solvation was considered by the continuum model based on density (SMD). The proposed workflow for the prediction rate of the participation coefficient unveiled the symmetric balance between the experimental data and the computational methods.

Matrix-Assisted DOSY for Analysis of Indole Alkaloid Mixtures

Diffusion-ordered spectroscopy (DOSY) is a powerful tool for investigating mixtures and identifying peaks of chemical components. However, similar diffusion coefficients of the components, particularly for complex mixtures that contain crowded resonances, limit resolution and restrict application of the DOSY technique. In this paper, matrix-assisted DOSY were used to explore whether the diffusion resolution of a complex model involving indole alkaloid mixtures can be realized. Furthermore, we investigated the influence of different factors on the separation effect. The results showed that the changes in diffusion coefficient differences were achieved more obviously when using sodium dodecyl sulfate (SDS) micelles as the matrix. In addition, we also found that increasing the concentration of SDS can improve the resolution of the DOSY spectrum. Finally, after investigating the influence factors and NMR conditions, we demonstrated the applications of the SDS-assisted DOSY on analyzing the total alkaloid extract of Alstonia Mairei, and the virtual separation of mixtures was achieved.

Time-resolved detection of SDS-induced conformational changes in α-synuclein by a micro-stopped-flow system

Dynamics of conformation changes of α-synuclein induced by the presence of SDS micelles are revealed using time-resolved diffusion, CD, and FRET measurements combined with a micro-stopped flow system.

Self-assemble Amphiphilic PEO-PPO-PEO Tri-block Co-polymeric Methotrexate Nanomicelles to Combat Against MCF7 Cancer Cells

Background: Methotrexate (MTX) is a water-insoluble, anti-tumor agent, causes adverse effects like bone marrow suppression, chronic interstitial obstructive pulmonary disease, hepatotoxicity, leukopenia, interstitial pneumonitis and nephrotoxicity with slow drug release rate. Objective: The present study was aimed for successfully incorporating of MTX into novel-targeted Pluronic (PEO-PPOPEO tri-block co-polymer) F127 polymeric micelles intended for intravenous administration with improved drug loading and sustained release behavior necessary to achieve better efficacy of MTX. Method: MTX-loaded Pluronic F127 micelles were characterized for critical micelle concentration, particle size and zeta potential, 1H NMR, drug loading, encapsulation efficiency characterization, cell uptake, in-vitro release study along with partition coefficient and solubilization thermodynamics. Results: The micellar formulation resulted in nano size 27.32±1.43nm of PF127/SDS, as compared to Pluronic F127 micelles or PF127/Phosphatidyl choline which were 30.52±1.18nm and 154.35±5.5nm respectively. The uptake of PF127/SDS micellar formulation incorporating Rhodamine 123 in MCF7 cancer cells was found to be higher (84.25%) than PF127/PC, PF127 and MTX i.e. 66.26%, 73.59% and 53% respectively. The in-vitro MTX release from PF127, PF127/SDS and PF127/PC polymeric micelles formulations was observed 69%, 69.5% and 66% at 12 h whereas 80.89%, 77.67% and 78.54% after 24 h respectively and reveals sustained release. MTX loaded PF127/SDS micelles showed high Partition coefficient and negative free energy of solubilization compared to PF127 and PF127/PC which signifies self-assembly behavior and thermodynamic stability towards dissociation to be higher. Conclusion: Finally concluded that MTX loaded PF127/SDS micelles act as a potential anticancer delivery system in comparison to PF127/PC and PF127 to combat against tumor cells by enhancing its cellular uptake targeting with sustained release pattern and reducing the thermodynamic instability. Thus, PF127/SDS micellar formulation can provide a useful alternative dosage form for intravenous administration of MTX.