Mass transfer process of peanut protein extracted by bis(2-ethylhexyl)sodium sulfosuccinate reverse micelles

The liquid-liquid extraction method using reverse micelles can simultaneously extract lipid and protein of oilseeds,which have become increasingly popular in recent years.However,there are few studies on mass transfer processes and models,which are helpful to better control the extraction process of oils and proteins.In this paper,mass transfer process of peanut protein extracted by bis(2-ethylhexyl)sodium sulfosuccinate(AOT)/isooctane reverse micelles was investigated.The effects of stirring speed(0,70,140,and 210 r/min),temperature of extraction(30,35,40,45,and 50℃),peanut flour particle size(0.355,0.450,0.600,and 0.900 mm)and solidliquid ratio(0.010,0.0125,0.015,0.0175,and 0.020 g/mL)on extraction rate were examined.The results showed that extraction rate increased with temperature rising,particle size reduction as well as solid-liquid ratio increase respectively,while little effect of stirring speed(P>0.05)was observed.The apparent activation energy of extraction process was calculated as 10.02 kJ/mol and Arrhenius constant(A)was 1.91 by Arrhenius equation.There was a linear relationship between reaction rate constant and the square of the inverse of initial particle radius(1/r_(0)^(2))(P<0.05).This phenomenon and this shrinking core model were anastomosed.In brief,the extraction process was controlled by the diffusion of protein from the virgin zone interface of particle through the reacted zone and it was in line with the first order reaction.Mass transfer kinetics of peanut protein extracted by reverse micelles was established and it was verified by experimental results.The results provide an important theoretical guidance for industrial production of peanut protein separation and purification.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Pharmacokinetics of a ternary conjugate based pH-responsive 10-HCPT prodrug nano-micelle delivery system

A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.

Analysis on the Characteristic Properties of PEDOT Nano-particle Based on Reversed Micelle Method

Based on the study of a new type of conducting polymer poly （3,4-ethylenedioxythiophene） （PEDOT）,we focussed on the preparation and characteristics of PEDOT nanoparticles made by reversed micelle method.Moreover,we deeply investigated the optical,electrical and the thermal stability of PEDOT nanoparticles.The main results are as follows： the small-sized PEDOT nanoparticles were prepared and utilized by different methods,such as ultraviolet/visible （UV-Vis） spectroscopy,Fourier-transform infrared （FT- IR） spectrum,scanning electron microscopy（SEM） and so on.The results show that the amount of oxidizer,ultrasonic treatment,polymerizing temperature and doping degree can influent morphology,electrical ability and gas sensitivity of PEDOT nanoparticles.The Bragg peaks of nanoparticles at 6.7°,12.7°,25° were observed by XRD and the better orientation of molecular chain was attributed to the effective doping of toluene-p-sulfonic acid,which also resulted in an enhancement of thermal stability of nanoparticles than conventional PEDOT.

TR-ESR Investigation on Reaction of Vitamin C with Excited Triplet of 9,10-phenanthrenequinone in Reversed Micelle Solutions

Time-resolved electron spin resonance has been used to study quenching reactions between the antioxidant Vitamin C （VC） and the triplet excited states of 9,10-phenanthrenequinone （PAQ） in ethylene glycol-water （EG-H2O） homogeneous and inhomogeneous reversed micelle solutions. Reversed micelle solutions were used to be the models of physiological environment of biological cell and tissue. In PAQ/EG-H2O homogeneous solution, the excited triplet of PAQ （3PAQ＊） abstracts hydrogen atom from solvent EG. In PAQ/VC/EG-H2O solution, 3pAQ＊ abstracts hydrogen atom not only from solvent EG but also from VC. The quenching rate constant of 3pAQ＊ by VC is close to the diffusion-controlled value of 1.41 × 108 L/（mol.s）. In hexadecyltrimethylammonium bromide （CTAB）/EG-H2O and aerosol OT （AOT）/EG- H2O reversed micelle solutions, 3pAQ＊ and VC react around the water-oil interface of the reversed micelle. Exit of 3pAQ＊ from the lipid phase slows down the quenching reaction. For Triton X-100 （TX-100）/EG-H2O reversed micelle solution, PAQ and VC coexist inside the hydrophilic polyethylene glycol core, and the quenching rate constant of 3pAQ＊ by VC is larger than those in AOT/EG-H2O and CTAB/EG-H2O reversed micelle solutions, even a little larger than that in EG-H2O homogeneous solution. The strong emissive chemically induced dynamic electron polarization of As＇- resulted from the effective TM spin polarization transfer in hydrogen abstraction of 3pAQ＊ from VC.

Synthesis and evaluation of cationic polymeric micelles as carriers of lumbrokinase for targeted thrombolysis

To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase(LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GP Ⅱ b/Ⅲ a expressed on the surface of membrane of activated platelet, LK loaded targeted micelles(LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly(2-(dimethylamino) ethyl methacrylate)(PCL-PDMAEMA), methoxy polyethylene glycol-block-polycaprolactone(mPEG-PCL)and RGDfk conjugated polycaprolactone-block-polyethylene glycol(PCL-PEG-RGDfk). PCLPDMAEMA was synthesized via ring open polymerization(ROP) and atom transfer radical polymerization(ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering(DLS) and transmission electron microscope(TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.

Rheological properties of wormlike micelles formed in the sodium oleate/trisodium phosphate aqueous solution

Aqueous solution of anionic surfactant,sodium oleate（NaOA）,was studied by means of steady-state shear rheology and dynamic oscillatory technique.The system of NaOA/Na3PO4 showed high viscosity,strong viscoelasticity and good ability of countering Ca^2＋,Mg^2＋.The Maxwell model and Cole-Cole plot were applied to study the dynamic viscoelasticity of wormlike micelles.The microstructures of the wormlike micelles were characterized by FF-TEM.

Preparation and evaluation of poly(L-histidine) based pH-sensitive micelles for intracellular delivery of doxorubicin against MCF-7/ADR cells

In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intracellular doxorubicin(Dox) delivery for cancer chemotherapy. Dox was loaded into the micelles by thin-film hydration method and a Box–Behnken design for three factors at three levels was used to optimize the preparations. The optimized mPEG-PLA-Phis/Dox micelles exhibited good encapsulation efficiency of 91.12%,a mean diameter of 45 nm and narrow size distribution with polydispersity index of 0.256.In vitro drug release studies demonstrated that Dox was released from the micelles in a p Hdependent manner. Furthermore, the cellular evaluation of Dox loaded micelles displayed that the micelles possessed high antitumor activity in vitro with an IC50 of 35.30 μg/ml against MCF-7/ADR cells. The confocal microscopy and flow cytometry experiments indicated that m PEG-PLA-Phis micelles mediated efficient cytoplasmic delivery of Dox with the aid of poly(Lhistidine) mediated endosomal escape. In addition, blank m PEG-PLA-Phis micelles were shown to be nontoxic to MCF-7/ADR cells even at a high concentration of 200 μg/ml. The pHsensitive mPEG-PLA-PHis micelles have been demonstrated to be a promising nanosystem for the intracellular delivery of Dox for MDR reversal.

pH-sensitive polymeric micelles triggered drug release for extracellular and intracellular drug targeting delivery

Most of the conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance of tumor cells and poor antitumor efficacy.Based on physiological differences between the normal tissue and the tumor tissue,one effective approach to improve the efficacy of cancer chemotherapy is to develop pH-sensitive polymeric micellar delivery systems.The copolymers with reversible protonationedeprotonation core units or acid-liable bonds between the therapeutic agents and the micelle-forming copolymers can be used to form pH-sensitive polymeric micelles for extracellular and intracellular drug smart release.These systems can be triggered to release drug in response to the slightly acidic extracellular fluids of tumor tissue after accumulation in tumor tissues via the enhanced permeability and retention effect,or they can be triggered to release drug in endosomes or lysosomes by pH-controlled micelle hydrolysis or dissociation after uptake by cells via the endocytic pathway.The pH-sensitive micelles have been proved the specific tumor cell targeting,enhanced cellular internalization,rapid drug release,and multidrug resistance reversal.The multifunctional polymeric micelles combining extracellular pH-sensitivity with receptor-mediated active targeting strategies are of great interest for enhanced tumor targeting.The micelles with receptor-mediated and intracellular pH targeting functions are internalized via receptor-mediated endocytosis followed by endosomal-pH triggered drug release inside the cells,which reverses multidrug resistance.The pH sensitivity strategy of the polymeric micelles facilitates the specific drug delivery with reduced systemic side effects and improved chemotherapeutical efficacy,and is a novel promising platform for tumor-targeting drug delivery.

EPR Effect of Amphiphilic Copolymer Micelles Observed by Fluorescent Imaging

Enhanced permeation and retention（EPR） targeting effect of rhodamine B labeled PEG-b-P（LA-co-DHP） [PEG：poly（ethylene glycol）;LA：L-lactide;DHP：2,2-dihydroxylmethyl-propylene carbonate] micelles（RhB-micelles） was observed in H22 liver cancer bearing mice.The RhB-micelles were prepared by conjugating rhodamine B with the DHP units of amphiphilic block copolymer PEG-b-P（LA-co-DHP） followed by subsequent self-assembling of the conjugate.The parent copolymer PEG-b-P（LA-co-DHP） was synthesized by ring-opening copolymerization of LA and DHP with PEG as macroinitiator and diethyl zinc（ZnEt2） as catalyst.The micelles have a spherical shape and the average diameter is ca.50 nm by TEM（transmission electron microscope） or 80 nm by DLS（dynamic light scattering）.Their in vitro cell uptake experiment by CLSM（confocal laser scanning microscopy） and flow cytometry showed preferential internalization of micelles by MCF-7 human breast cancer cells to free RhB.The in vivo tests by live animal imaging and ex vivo excised organ imaging showed that after vena tail injection,free RhB molecules were distributed in the whole body through the circulation system and then gradually metabolized and excreted and there was no preferential partition in tumor bed from the beginning to the end.But the RhB-micelles were preferentially distributed to the tumor bed so that their concentration（fluorescent intensity） in tumor bed got the level of the liver at a certain time point between 1 and 6 h and reached a maximum relative intensity at around 12 h,indicating an obvious EPR effect of RhB-micelles in H22 liver cancer.

Rheological properties of novel viscoelastic micelle systems containing anionic-nonionic dimeric surfactant

The viscoelastic micelle systems formed by novel anionic-nonionic dimeric surfactant and conventional cationic surfactant cetyltrimethylammonium(1631) were studied.The viscoelasticity,thixotropy,flow curves and constitutive equation for the novel viscoelastic micelle systems were investigated.The results show that the micelle systems possess viscoelasticity,thixotropy,and shear thinning property.Some micelle systems possess hysteresis loops showing both viscoelasticity and thixotropy.It is proved that the flow curves are characterized by the co-rotational Jeffreys constitutive equation correctly.

Improved Anti-tumor Efficiency against Prostate Cancer by Docetaxel-loaded PEG-PCL Micelles

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory prostate cancer（HRPC）. By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel（DTX）-loaded mPEG-PCL micelles（DTX-PMs）, with the purpose of eliminating side effects of the commercial formulation（Tween 80） and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of（8.72±1.05）%, and an encapsulation efficiency of（98.1±8.4）%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei, the DTX-PMs dramatically reduced the prostate specific antigen（PSA） level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

Different Aggregation Behaviors of Tetra-(4-hydroxyphenyl) Porphyrin (THPPH_2) in the Inner Core and on the Surface of CTAB Micelles

The UV-Vis spectra of THPPH2 in CTAB micelles at pH7.2 and pH11.0 were analyzed to study the effect of micellar environments on the aggregation behaviors of this porphyrin.

Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX)via polymeric nanocarriers to treat breast cancer.To this end,methoxyl poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PDLA)was prepared and characterized using FTIR and 1H NMR,and their molecular weights were determined by GPC.Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line(MCF-7 cells).Subsequently,RES and DTX were loaded in the mPEG-PDLA micelles simultaneously,and the morphology,particle size distribution,in vitro release,pharmacokinetic profiles,as well as cytotoxicity to the MCF-7 cells were characterized.IC50 of RES and DTX in MCF-7 cells were determined to be 23.0μg/ml and 10.4μg/ml,respectively,while a lower IC50 of 4.8μg/ml of the combination of RES and DTX was obtained.The combination of RES and DTX at a ratio of 1:1(w/w)generated stronger synergistic effect than other ratios in the MCF-7 cells.RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles,and enhanced cytotoxicity in vitro against MCF-7 cells.The AUC(0→t)of DTX and RES in mPEG-PDLA micelles after i.v.administration to rats were 3.0-fold and 1.6-fold higher than that of i.v.injections of the individual drugs.These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.

New Development of Reverse Micelles and Applications in Protein Separation and Refolding

Reverse micelles bring mild and effective microenvironments in organic solvent that contain bitmolecules, which have attracted immense attention for application in the isolation of proteins, protein refolding, and enzymatic reaction. In this review, the application of reverse micelles for protein separation and refolding has been briefly summarized and various reverse micellar systems composed of different surfactants, including ionic, non- ionic, mixed, and affinity-based reverse micelles, have been highlighted. It illustrates especially the potential application of the novel affinity-based reverse micelles consisting of biocompatible surfactant coupled with affinity ligands. Moreover, the importance to develop universal affinity-based reverse micelles for protein separation and refolding in the downstream processing of biotechnology has been pointed out.

Evaluation of micelles incorporated into thermosensitive hydrogels for intratumoral delivery and controlled release of docetaxel:A dual approach for in situ treatment of tumors

The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period. DTX-micelles(docetaxel-loaded mixed micelles) are able to increase the solubility of DTX inwater, and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels. The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles) can accelerate the formation of a depot of this drug-loaded system at the siteof administration. Therefore, the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection. An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety. In conclusion, theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem, with higher tumor inhibition effects and are less toxic to normal tissues.

Mechanisms of Cytochrome C Extraction by Reverse Micelles

The extraction of cytochrome C was carried out by means of phase transfer technique with three different reverse micellar systems, i.e. , a CTAB micellar solution in n butyl alcohol chloroform(volume ratio 4∶1), an AOT micellar solution in isooctane and a SDSS D 2EHPA micellar solution in isooctane. The extraction mechanisms were studied. The results show that the extraction mechanisms for the same proteins with different types of reverse micellar systems can be distinct. The extraction of cytochrome C with CTAB and SDSS D 2EHPA reverse micellar systems are carried out according to the mechanism of electrostatic interaction. However, in the extraction of cytochrome C with the AOT reverse micellar system, the electrostatic interaction between the protein and the surfactant is not important.

Optically active micelles from self-assembly of MPEG-b-PMALM copolymer in water

Reported here is fabrication of optically active micelles with broad range of morphologies in water, such as spheres, cylinders, and vesicles, from self-assembly of poly（ethylene glycol） monomethyl ether-b-poly- （methacryloyl-L-leucine methyl ester） （MPEG-b-PMALM） copolymer, which was prepared via atom transfer radical polymerization （ATRP） from vinyl monomer bearing chiral amino acid moieties, N-methacryloyl L-leucine methyl ester （MALM）, using bromine （Br） end-capped poly（ethylene golycol） monomethylether （MPEG-Br） as macroinitiator in the presence of CuBr/Me6TREN as catalytic system.

Study of the Electrical Double Layer of a Spherical Micelle: Functional Theoretical Approach

By using the iterative method in functional theory, an analytic expression of the Poisson-Boltzmann equation (PB eq.), which describes the distribution of the potential of electrical double layer of a spherical micelle, has been carried out under the general potential condition for the first time. The method also can give the radius, the surface potential, and the thickness of the layer.

Microwave-assisted Palladium-micelle-catalyzed Suzuki Cross-coupling Reaction in Water

A microwave-accelerated Suzuki coupling procedure was developed via guanidinium ionic liquids（GILs） stabilized Pd-micelle.The Pd micelle/GILs play a key role in enhancing the activity,due to the highly dispersed Pd active sites and the phase transfer function of GILs,which ensures the adsorption of reactants and facilitates the translation of the intermediates to the surface of the micelle.