Polymeric nanocapsules ultra stable in complex biological media

Non-specific protein adsorption from complex biological media, especially from blood plasma, is an urgent challenge for the application of nanoparticles as delivery systems, diagnostics, and other biomedical application. Nanocapsules (NC) prepared from FDA-approved degradable poly(ɛ-caprolactone) shell and Mygliol 812^® oil in the core were coated with mono-methoxy terminated oligo(ethylene glycol) methacrylate (poly(MeOEGMA)) polymer brush layers with a well-controlled thickness at the nanometer scale up to 350 nm using surface initiated atom transfer radical polymerization in water or phosphate buffered saline. Incubation of uncoated NC with human serum albumin solution, fetal bovine serum, or human blood plasma resulted in fast aggregation observed by dynamic light scattering as an increase in diameter of particles present in the solutions. Conversely, these biological fluids affected only marginally the size distribution of the NC coated with a 60 nm thick poly(MeOEGMA) layer. The high suspension stability of the coated NC in complex biological fluids was related to the suppressed deposition of proteins from these fluids observed by surface plasmon resonance (SPR) on analogous poly(MeOEGMA) layer prepared on flat surfaces of SPR chips.     

Water-soluble octahedral polyammonium nanocapsules: synthesis and encapsulation studies

The syntheses of two water-soluble octahedral polyammonium nanocapsules 5e and 5f are described. Nanocapsule 5e was prepared via the TFA-catalyzed condensation reaction of six MOM-protected 4-hydroxybutyl-footed tetraformyl cavitands 3c with 12 ethylene diamines, followed by reduction and acidic hydrolysis of the intermediate octahedral polyimino nanocapsule. Nanocapsule 5f was prepared from 5e via the oxidation of the 4-hydroxybutyl feet to 3-carboxypropyl feet. Both nanocapsules are soluble in water below pH 5. 5f is also water-soluble above pH 7. In acidic aqueous solution, nanocapsule 5e encapsulates small negatively charged, partially hydrophobic guests, such as p-toluenesulfonic acid, N-BOC-aspartic acid, or 4-methylumbelliferyl phosphate. The single site microscopic binding constants for the latter guests are 150±30, 510±50, 1550±150 M⁻¹, respectively and were determined from ¹H NMR titrations and DOSY experiments by assuming a 6:1 binding model with six identical, independent binding sites per nanocapsule (statistical binding). 5e doesn't bind small neutral hydrophobic molecules in aqueous solution. However, both nanocapsules bind to nucleotides, such as ATP, dAMP, dGMP or TTP. NMR experiments support that nucleotides are not encapsulated, but bind to the outside of the nanocapsules.     

Nanoporous microbead supported bilayers: stability, physical characterization, and incorporation of functional transmembrane proteins

The introduction of functional transmembrane proteins into supported bilayer-based biomimetic systems presents a significant challenge for biophysics. Among the various methods for producing supported bilayers, liposomal fusion offers a versatile method for the introduction of membrane proteins into supported bilayers on a variety of substrates. In this study, the properties of protein containing unilamellar phosphocholine lipid bilayers on nanoporous silica microspheres are investigated. The effects of the silica substrate, pore structure, and the substrate curvature on the stability of the membrane and the functionality of the membrane protein are determined. Supported bilayers on porous silica microspheres show a significant increase in surface area on surfaces with structures in excess of 10 nm as well as an overall decrease in stability resulting from increasing pore size and curvature. Comparison of the liposomal and detergent-mediated introduction of purified bacteriorhodopsin (bR) and the human type 3 serotonin receptor (5HT3R) are investigated focusing on the resulting protein function, diffusion, orientation, and incorporation efficiency. In both cases, functional proteins are observed; however, the reconstitution efficiency and orientation selectivity are significantly enhanced through detergent-mediated protein reconstitution. The results of these experiments provide a basis for bulk ionic and fluorescent dye-based compartmentalization assays as well as single-molecule optical and single-channel electrochemical interrogation of transmembrane proteins in a biomimetic platform.     

Chitosan-based solid electrolyte composite membranes: I. Preparation and characterization

Some chitosan-based solid electrolyte composite membranes were prepared by incorporating potassium hydroxide as the functional ionic source, using glutaraldehyde as cross-linking agent. A three-layer structure with a porous intermediate layer for each composite membrane was observed using SEM. It was found that the concentration of potassium hydroxide solution used to prepare the composite membranes largely influenced the pore volume, porosity, pore size of the intermediate layer, as well as determined the content of potassium hydroxide inside the composite membranes, whereas the degree of cross-linking of composite membrane did not show notable effects. All composite membranes showed significant decreases in both their T_g and onset thermal degradation temperatures with respect to the solid cross-linked chitosan membranes without containing potassium hydroxide. Potassium hydroxide was found to be located inside the intermediate layer of composite membranes with shapes of bulky or fabric crystals. The crystalline properties of matrices of the composite membranes themselves were remarkably modified after being incorporated with potassium hydroxide and main crystalline peaks of matrices almost disappeared for all composite membranes.     

Novel core-shell lipid-chitosan and lipid-poloxamer nanocapsules: stability by hydration forces

In the last few years, a great attention has been paid to core-shell structured lipid nanocapsules. The interest of these colloids lies in their very promising applications as delivery systems of hydrophobic drugs or as DNA carriers. The aim of this work was to provide fuller knowledge concerning the physicochemical properties of these new colloidal particles, paying special attention to the role played by the constituting components. Our lipid nanocapsules were comprised of a triglyceride-lecithin core surrounded by a chitosan and/or poloxamer (Pluronic® F68) shell. Four different systems were formulated by varying the chitosan and poloxamer contents. We have estimated their shell composition from electrokinetic mobility measurements and stability studies. They revealed a high incorporation of chitosan to the shell, while Pluronic® F68 only presented a secondary role during the nanocapsule formation, providing final systems with low poloxamer content. In addition, the stability studies, performed not only on ideal solutions but also on simulated physiological fluids, revealed that hydration forces were crucial to maintain the integrity of these nanocapsules under physicochemical conditions similar to those found in real physiological fluids. Theoretical treatment of stability data has allowed us to determine the role that ions play on hydration forces when they act as counterions.     

Chitosan-based adsorbents for analytical sample preparation and removal of pollutants from aqueous media: Progress,challenges and outlook

The development of greener and more efficient materials for extracting environmental contaminants from various matrices is a growing area of research. Materials that do not cause secondary pollution are highly desirable in such applications. Chitosan (CS) is a non-toxic biopolymer enriched with amino and hydroxyl groups, used not only for extracting pollutants but also for crosslinking and functionalizing CS with other materials. The composites of CS with carbon, metal-organic frameworks, metal and metal oxide nanoparticles, and magnetic materials have been used to extract various inorganic and organic analytes in aqueous samples. CS-based sorbents have been evaluated across multiple extraction techniques, such as dispersive solid phase extraction, magnetic solid phase extraction, solid phase microextraction, syringe solid phase extraction, membrane-protected solid phase extraction, and others. This review offers an overview of the CS-based sorbents in analytical extractions, highlighting their strengths, weaknesses, and potential solutions. At the end, a brief overview of the CS-based adsorbents in water treatment applications is also provided.     

Oxadiazole: Synthesis,characterization and biological activities

The synthesis of novel achiral and chiral amides incorporating 1,3,4-oxadiazole ring are reported. All the synthesized amides are characterized ¹H, ¹³C, FTIR and elemental analysis techniques. Synthesized compounds are screened for microbial and cytotoxic activities.     

Protein encapsulation in mesoporous silicate: the effects of confinement on protein stability, hydration, and volumetric properties

On the basis of the predictions of statistical-thermodynamic models, it is postulated that excluded volume effects may play a significant role in the stability, interaction, and function of proteins. We studied the effects of confinement on protein un/refolding and stability. Our approach was to encapsulate a model protein, RNase A, in a mesoporous silica, MCM-48, with glasslike wall structure and with well-defined pores to create a crowded microenvironment. To the best of our knowledge, this is the first report where pressure perturbation and differential scanning calorimetric techniques are employed to evaluate the stability, hydration, and volumetric properties of the confined protein. A drastic increase in protein stability ( approximately 30 degrees C increase in unfolding temperature) is observed. The increase in stability is probably not only due to a restriction in conformational space (excluded volume effect due to nonspecific interactions) but also due to an increased strength of hydration of the protein within the narrow silica pores.     

Synthesis and characterization of novel biocompatible nanocapsules encapsulated lily fragrance

In this study, novel biocompatible nanocapsules encapsulated lily fragrance (LF-NPs) were development. And, the LF-NPs are expect to have many potential applications to our daily life, such as cosmetic decorative, food industry, antibacterial, medical industry, tobacco industry, textile industry, home life, and so on.     

Electrochemical and spectroscopic characterization of organic compound uptake in silica core-shell nanocapsules

Oil-filled silica nanocapsules consisting of a hydrophobic liquid core and a silicate shell have been shown to efficiently extract hydrophobic compounds from aqueous media. With a view toward quantifying the selectivity of these systems, a series of electrochemical and spectroscopic measurements was performed. Uptake and kinetics experiments were carried out through electrochemical measurements by using solutions of lipophilic electroactive molecules of different sizes and with different affinities for silica. Other solutions with fluorescent probes were used for spectrophotometry measurements. In this work we report the environment where the lipophilic compounds studied end up after absorption and the kinetics of their uptake by the oil-filled silica nanocapsules with different shell thicknesses.     

Single-crystalline gold microplates: synthesis, characterization, and thermal stability

Single-crystalline gold microplates of several 10 microm in lateral size, characterized by hexagonal, truncated triangular, and triangular shapes with (111) planes as two basal surfaces, have been synthesized in large quantities through a solution phase process. Significantly, such anisotropic Au nanostructures exhibit remarkable optical properties, in which the dipole plasmon resonance shifting in the NIR region and the quadrupole plasmon resonance at approximately 820 nm were observed. Fragmentation of Au microplates is found when the temperature is higher than 450 degrees C, indicating they are not thermodynamically stable structure at high temperature. Investigations on the Au microplates upon heating suggest that the melting and collapsing start mainly at the edges that should be Au (110) facets. This work is valuable for Au nanostructures applied at elevated temperatures.     

Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence imaging of cisplatin encapsulation, stability, cellular uptake, and toxicity

Cisplatin is the most effective cytotoxic agent against many cancers. Its usage, however, is limited due to inefficient uptake by the target cells. A liposomal formulation of cisplatin is reported to partly overcome this limitation. Physicochemical characteristics of the liposome-cisplatin preparation, including its size, stability, encapsulation efficiency, and cytoplasmic internalization efficiency, play a significant role in an effective usage of liposomal formulations. We have used atomic force microscopy (AFM) to determine physicochemical characteristics of cisplatin-encapsulated liposomes, AFM and fluorescence microscopy to examine their cytoplasmic internalization, and Live/Dead assay to examine their cell toxicity. Nonencapsulated cisplatin is globular and 10-50 nm in size. AFM force-dissection and stiffness measurements show that cisplatin-encapsulated liposomes are significantly stiffer ( approximately 100%) and more stable than liposomes without encapsulated cisplatin. Cisplatin-encapsulated liposomes of approximately 250 nm diameter (nanoliposomes) are most efficiently internalized and induce cell toxicity in a time-dependent manner. Liposomes without cisplatin of similar dimensions, although internalized in the cell cytoplasm, do not induce cell toxicity.     

Rhodanine-based biologically active molecules: synthesis,characterization, and biological evaluation

To investigate the antimicrobial properties of the rhodanine (2-thioxo-4-thiazolidinone) structure, several 2-[(5Z)-5-benzylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-phenylacetamide derivatives were synthesized by use of an efficient procedure. Variation of the functional group on the 5-benzylidine ring of rhodanine led to compounds containing a 2-thioxo-4-thiazolidinone group attached to N-phenyl acetamide. The chemical structures of the compounds were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy, ESI mass spectrometry, and elemental analysis. The antibacterial and antifungal activity of the compounds were tested, at seven concentrations, against Gram-positive bacterial strains (Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922), Gram-negative bacterial strains (Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC 11774), and fungal strains (Candida albicans ATCC 66027 and Aspergillus niger ATCC 6275), by use of the Kirby Bauer disk-diffusion technique and the serial broth dilution technique. The results obtained were compared with those for reference drugs. Relationships between structure and their antimicrobial activity are discussed.