DPPC/poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) chimeric nanostructures as potential drug nanocarriers

In this study, we report on the self assembly behavior and on stability studies of mixed (chimeric) nanosystems consisting of dipalmitoylphosphatidylcholine (DPPC) and poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) gradient copolymer in aqueous media and in fetal bovine serum (FBS). A gamut of light scattering techniques and fluorescence spectroscopy were used in order to extract information on the size and morphological characteristics of the nanoassemblies formed, as a function of gradient block copolymer content, as well as temperature. The hydrodynamic radii (R _h) of nanoassemblies decreased in the process of heating up to 50 °C, while the fractal dimension (d _f) values, also increased. Indomethacin was successfully incorporated into these chimeric nanocarriers. Drug release was depended on the components ratio. The present studies show that there are a number of parameters that can be used in order to alter the properties of chimeric nanosystems, and this is advantageous to the development of “smart” nanocarriers for drug delivery.     

Morphological diversity of block copolymer/lipid chimeric nanostructures

Different in nature biomaterials, which are used for the development of drug delivery nanosystems, could be mixed, in order to produce chimeric/mixed nanostructures. Their morphological characteristics and biophysical properties depend on the degree of association and interactions between the self-assembling biomaterials. For the purpose of this study, chimeric nanosystems composed of phospholipid and amphiphilic diblock copolymers were developed, at different molar ratios. Light scattering and imaging techniques were employed, in order to extract information on the nanostructure physicochemical characteristics and their morphology. Certain morphological characteristics were assessed for vesicle membranes, which are considered to be of paramount importance for their fate inside the physiological environment and their biophysical behavior. Besides vesicles, a variety of structures appeared in the phospholipid/copolymer chimeric systems, depending on both the composition and the concentration of the utilized polymer, declaring the lyotropic effect on the self-assembly of the biomaterials. The size range of most objects, including vesicles, was around 100 nm. Membrane irregularities, such as domains and rafts, are considered as functional biophysical factors, rendering liposomes appropriate artificial models for approaching various diseases on the level of living cell membranes. Such information is of paramount importance for the utilization of chimeric nanostructures in drug delivery and in therapy.

Open image in new window

Graphical abstract

Combining of different in nature biomaterials, e.g. phospholipid and amphiphilic polymer, leads to divergent morphogenesis, concerning both structural conformation and membrane morphology.

     

Production and rheological characterization of biopolymer of Sphingomonas capsulata ATCC 14666 using conventional and industrial media

This work was aimed at the production and rheological characterization of biopolymer by Sphingomonas capsulata ATCC 14666, using conventional and industrial media. The productivity reached the maximum of 0.038 g/L·h, at 208 rpm and 4% (w/v) of sucrose. For this condition, different concentrations of industrial medium were tested (2.66, 4, 6, and 8%). The best productivity was obtained using pretreated molasses 8% (w/v) (0.296 g/L·h), residue of textured soybean protein 6% (wt/v) (0.244 g/L·h) and crude molasses 8% (w/v) (0.192 g/L·h), respectively. Apparent viscosity presented similar results when compared with those in the literature for other biopolymers.     

The physicochemical/thermodynamic balance of advanced drug liposomal delivery systems

The aim of this work is to study the morphological characteristics via fractal analysis and the alterations of the thermotropic behavior of dipalmitoylphosphatidylcholine (DPPC) liposomes, caused by the incorporation of cholesterol, poly(amidoamine) (PAMAM) dendrimer, and MPOx (poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline)) gradient block copolymer (9:1 molar ratio). A gamut of light scattering techniques and differential scanning calorimetry were used in order to extract information on the morphological (in different dispersion media) and thermodynamic characteristics of liposomal drug nanocarriers, respectively. The vesicles’ structure of liposomes has a different thermodynamic content, which corresponds to a different thermotropic behavior, in comparison to pure lipid bilayers. The observed metastable phase only for DPPC liposomes has been considered as a “physical impurity”, which leads to “physical incompatibility” and consequently promotes the aggregation of DPPC liposomes in aqueous media. The incorporation of biomaterials such as PAMAM G4 and MPOx, caused alterations in the thermotropic behavior of DPPC liposomes affecting only the main transition specific enthalpy ΔH. All the other calorimetric parameters remained unaltered. These findings supported the hypothesis that the exceptional stability and transition cooperativity of the chimeric liposomal membrane might be due to the reduction of the vesicle size with the smaller membrane curvature that is indicated by the fractal dimensionality of the system. In conclusion, the results from the thermal analysis of the liposomal systems were in line with the picture of their structural characteristics, as indicated by the interplay between physicochemical and thermodynamical parameters, which determines their fractal morphology.     

Production of insoluble exopolysaccharide of Agrobacterium sp. (ATCC 31749 and IFO 13140)

Agrobacterium isolated from soil samples produced two extracellular polysaccharides: succinoglycan, an acidic soluble polymer, and curdlan gum, a neutral, insoluble polymer. Maize glucose, cassava glucose, and maize maltose were used in fermentation medium to produce insoluble polysaccharide. Two Agrobacterium sp. strains which were used (ATCC 31749 and IFO 13140) in the production of insoluble exopolysaccharide presented equal or superior yields compared to the literature. The strain ATCC 31749 yielded better production when using maize maltose, whose yield was 85%, whereas strain IFO 13140 produced more when fed maize glucose, producing a yield of 50% (on reducing sugars).     

Lysozyme complexes with thermo- and pH-responsive PNIPAM-<Emphasis Type="Italic">b</Emphasis>-PAA block copolymer

Lysozyme is an enzyme responsible for the damage of bacterial cell walls and is abundant in a number of secretions such as tears and human milk. In the present study, we investigated the structure, the physicochemical characteristics, and the temperature-responsiveness of lysozyme complexes with poly(N-isopropylacrylamide)-b-poly(acrylic acid) block polyelectrolyte in aqueous media. A gamut of light-scattering techniques and fluorescence spectroscopy were used in order to examine the complexation process, as well as the structure, solution behavior, and temperature response of the nanosized complexes. The concentration of copolymer polyelectrolyte was kept constant. The values of the scattering intensity, I ₉₀, which is proportional to the mass of the species in solution, increased gradually as a function of C _LYS, providing proof of the occurring complexation, while the size of the nanostructures decreased. The structure of the complexes became more open as the C _LYS increased. The increase of the salinity did not affect the structural characteristics of the supramolecular nanoparticulate aggregates. On the other hand, the physicochemical and structural characteristics of the complexes changed upon increasing temperature, and the changes depended on the initial ratio block polyelectrolyte/lysozyme. The knowledge on developing block polyelectrolyte/protein complexes through electrostatic interactions, obtained from this investigation, may be applied to the design of nutraceuticals.