We report pH-responsive liquid crystalline lipid nanoparticles, which are dual loaded by Brucea javanica oil (BJO) and doxorubicin hydrochloride (DOX) and display a pH-induced inverted hexagonal (pH=7.4) to cubic (pH6.8) phase transition with a therapeutic application in cancer inhibition. Brucea javanica oil is a traditional herbal medicine that strongly inhibits the proliferation and metastasis of various cancers. Doxorubicin is an anti-tumor drug, which prevents DNA replication and hampers protein synthesis through intercalation between the base pairs of the DNA helices. Its dose-dependent cardiotoxicity imposes the need of safe delivery carriers.Here pH-induced changes in the structural and interfacial properties of designed multicomponent drug delivery (monoolein-oleic acid-BJO-DOX) systems are determined by synchrotron small-angle X-ray scattering (SAXS) and the Langmuir film balance technique. The nanocarrier assemblies displayed good physical stability in the studied pH range and adequate particle sizes and zeta potentials. Their interaction with model lipid membrane interfaces was enhanced under acidic pH conditions, which mimic the microenvironment around tumor cells. In vitro cytotoxicity and apoptosis studies with BJO-DOX dual-loaded pH-switchable liquid crystalline nanoparticles (BJO-DOX-LCNPs) were performed with the human breast cancer MCF-7 cells line and MCF-7 cells with doxorubicin resistance (MCF-7/DOX), respectively. The obtained pH-sensitive nanomedicines demonstrated enhanced anti-tumor efficacy. The performed preliminary studies suggested a potential reverse of the resistance of the MCF-7/DOX cells to DOX. These results highlighted the necessity of further understanding of the link between the established pH-dependent drug release profiles of the nanocarriers and the role of their pH-switchable inverted hexagonal, bicontinuous cubic, sponge or emulsified emulsion inner organizations for the therapeutic outcomes.
Many phytochemical antioxidant compounds, including curcumin (CU), are water-insoluble and thus require delivery carriers in order to increase their bioavailability for in vivo applications. Oxidative stress-related apoptosis is a common cause for the neuronal loss in the progression of neurodegenerative diseases. Lipid nanoparticles (NPs) with internal self-assembled liquid crystalline structures present strong interest as safe drug delivery systems for neuronal regeneration through combination therapies. Here, we report spongosome and cubosome lipid NPs, which co-encapsulate CU and fish oil (FO), rich in ω-3 polyunsaturated fatty acids. The performed structural investigation by synchrotron small-angle X-ray scattering evidenced the liquid crystalline organization of the self-assembled NPs. The encapsulation efficiency for CU in the lipid nanocarriers was found to be higher as compared to that reported for polymer-based carriers. The cytotoxicity of the blank and antioxidant-loaded nanocarriers was negligible at lipid concentrations 300 and 500 nM. Morphological changes were observed for neuronally derived human SH-SY5Y cells subjected to damage by reactive oxygen species (ROS) upon exposure to hydrogen peroxide. Using flow cytometry, we quantified the effects of CU and FO, co-encapsulated in spongosome and cubosome lipid NPs on the response of differentiated SH-SY5Y cells to H 2 O 2 -induced oxidative stress. Measurements of the intracellular ROS levels (using a 2′,7′dichlorodihydrofluorescein diacetate probe) and of apoptotic cells (using an Annexin V-PE/SYTOX-green assay) were performed to compare the neuroprotective potential of the liquid crystalline spongosome and cubosome nanocarriers to that of ethanolic solutions or aqueous suspensions of the CU/FO mixtures. The results indicated that dual drug-loaded cubosomes may be suitable for combination treatments against neurodegenerative disorders.(1) Brookmeyer, R.; Abdalla, N.; Kawas, C. H.; Corrada, M. M. Forecasting the prevalence of preclinical and clinical Alzheimer's disease in the United States.
Structural control over design and formation of self‐assembled nanomaterials for neuroprotection and neuroregeneration is crucial for their application in nanomedicine. Here a synthetic construct of the pituitary adenylate cyclase‐activating polypeptide (PACAP38) coupled to a docosahexaenoic acid (DHA: an ω‐3 polyunsaturated fatty acid (PUFA)) is designed towards the creation of compartmentalized liquid crystalline assemblies of neuroprotective compounds. The hormone PACAP38 is a ligand of the class B PAC1 G‐protein‐coupled receptor (GPCR), whereas DHA is a lipid trophic factor. The lipidated peptide PACAP‐DHA is co‐assembled into hierarchical nanostructures elaborated from hybrid vesicle‐micelle reservoirs as well into PEGylated cubosomes composed of multiple neuroprotective building blocks. The resulting nanostructures are determined by synchrotron small‐angle X‐ray scattering (BioSAXS) and cryogenic transmission electron microscopy (cryo‐TEM). Multicompartment topologies are obtained in a two‐fold approach: (i) intriguing compartmentalized vesicles, which embed pep‐lipid micelles forming nanopatterns, and (ii) multidomain pep‐lipid cubosomes. Both kinds of topologies are favorable for sustained‐release applications in combination therapies of neurodegeneration. The organizational complexity of the scaffolds involving the lipidated high‐molecular weight peptide hormone is beyond the one that has been reached with small lipid‐like peptide surfactants.
This paper is an in-depth analysis devoted to two basic types of water based magnetic fluids (MFs), containing magnetite nanoparticles with electrostatic and with electro-steric stabilization, both obtained by chemical coprecipitation synthesis under atmospheric conditions. The two sets of magnetic fluid samples, one with citric acid (MF/CA) and the other with oleic acid (MF/OA) coated magnetic nanoparticles, respectively, achieved saturation magnetization values of 78.20 kA m-1 for the electrostatically and 48.73 kA m-1 for the electro-sterically stabilized aqueous ferrofluids which are among the highest reported to date. A comprehensive comparative analysis combining electron microscopy, X-ray photoelectron spectroscopy, attenuated total reflectance Fourier transform infrared spectroscopy, vibrating sample magnetometry, small-angle X-ray and neutron scattering, dynamic light scattering and magneto-rheometry revealed similarities and essential differences on the microscopic and macroscopic level between the two kinds of water-based ferrofluids. While the saturation magnetization values are quite different, the hydrodynamic volume fractions of the highest concentration MF/CA and MF/OA samples are practically the same, due to the significantly different thicknesses of the particles' coating layers. The results of volume fraction dependent structure analyses over a large concentration range by small-angle X-ray and neutron scattering, correlated with magneto-rheological investigations for the electrostatically stabilized MFs, demonstrate formation of short chains of magnetic nanoparticles which are relatively stable against coagulation with increasing concentration, while for MFs with electro-steric stabilization, magnetic field and shear rate dependent loosely bound structures are observed. These particle structures in MF/OA samples manifest themselves already at low volume fraction values, which can be attributed mainly to magnetic interactions of larger size particles, besides non-magnetic interactions mediated by excess surfactant.
Physicochemical and antibacterial properties of native and modified whey proteins at pH 2 to 7 Highlights • Whey protein isolate was covalently modified with allyl isothiocyanate • The adducts showed increased hydrophobicity at pH 2, 4 and 6 • The protein β-sheet content increased • Interfacial tension was reduced • Antimicrobial activity of WPI was not significantly influenced
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