Carriers Of Bioactive Compounds Research Articles

Biocompatible nanodispersions as delivery systems of food additives: A structural study

Nanodispersions based on food grade biocompatible materials were developed and structurally characterized to be used as carriers of bioactive compounds with specific nutritional value. The main idea was to formulate concentrated solutions of specific food components at the nanoscale to be consumed either on their own or as integrating parts of classic foods, upon aqueous dilution. For this purpose microemulsions consisting of (R)-(+)-limonene/ethanol/Tween 40/water/propylene glycol were formulated in the presence and in the absence of squalene, gallic acid and octyl gallate. The limits of the single-phase region as described by pseudo-ternary phase diagrams were related to the nature of the food additive. The more extended monophasic region was obtained when octyl gallate was added in the system. Interfacial properties of the microemulsions were studied by electron paramagnetic resonance (EPR) spectroscopy employing the nitroxide spin probe 5-doxylstearic acid (5-DSA). In general guest molecules decreased the flexibility of the surfactant monolayer as manifested from the calculation of rotational correlation time (τR) and order parameter S of 5-DSA. Particle size measurements were performed using dynamic light scattering (DLS) and oil droplet diameters in the range of 11.7 to 17.4nm were observed. The addition of squalene resulted in the formulation of larger oily droplets whereas octyl gallate formed smaller ones. Finally SAXS experiments provided qualitative information of o/w microemulsions showing squalene solubilization in the dispersed oily phase, octyl gallate localization on the membrane and gallic acid solubilization in the continuous aqueous phase.

Surfactant-rich biocompatible microemulsions as effective carriers of methylxanthine drugs

Under the perspective of their potential pharmaceutical applications, new surfactant-rich biocompatible microemulsions were prepared and structurally characterized to be used as novel carriers of theophylline and theobromine. The existence of single phase regions was investigated in pseudo-ternary phase diagrams of three different microemulsion systems: (1) isopropyl palmitate/Triton X-100/water+propylene glycol, (2) Miglyol 818/Triton X-100/water+propylene glycol and (3) isopropyl palmitate/Triton X-100+Span 20/water+propylene glycol. Electrical conductivity measurements indicated the formation of water-in-oil (w/o) structures. Interfacial properties of the microemulsions were studied by electron paramagnetic resonance (EPR) spectroscopy employing the nitroxide spin probe 5-doxylstearic acid (5-DSA). The determined order parameter and wobbling angle showed that the system composition influences the membrane flexibility whereas drug incorporation resulted in more flexible membranes. Particle size measurements were performed using dynamic light scattering (DLS) showing that addition of the drugs resulted in the formulation of larger aqueous droplets. To evaluate the ability of the proposed microemulsions to serve as carriers of bioactive compounds for topical administration, in vitro permeation studies were carried out using the Franz type diffusion cells and a model membrane. The nature of the oil and the surfactant used for the construction of the microemulsions affected the phase behavior, the size and also the interfacial properties of both free and loaded systems. Drug permeation studies revealed the effectiveness of the proposed formulations as carriers of theophylline and theobromine.

Electrospun composite fibers of polyvinylpyrrolidone with embedded poly(methyl methacrylate)–polyethyleneimine core–shell particles

Composite fibers consisting of poly(methyl methacrylate)–polyethyleneimine (PMMA–PEI) core–shell particles embedded in polyvinylpyrrolidone (PVP) were successfully fabricated by the electrospinning method. The electrospun fibers were produced using 18 % w/v aqueous PVP solution blended with 2 % w/v PMMA–PEI particles at various pH (1, 2, 3, and 4) with a fiber collection distance set at 10 cm. The applied electrical voltages (10, 12, 14, and 16 kV) significantly affected the morphology and diameter of the prepared composite fibers (141–353 nm). The smallest composite fibers were obtained from the spinning mixture at pH 2 and a voltage of 14 kV. The composite fibers would potentially be applied as drug and bioactive compound carriers.

Effect of different treatments on the ability of α-lactalbumin to form nanoparticles

Nanoparticles of bovine α-lactalbumin (α-LA) prepared by desolvation and glutaraldehyde crosslinking are promising carriers for bioactive compounds in foods. The objective of this work was to study the effect of changes in hydrophobic interactions by using different desolvating agents (acetone, ethanol, or isopropanol) and the use of a heat or high-pressure treatment step before the desolvation process on the size, structure, and properties of α-LA nanoparticles. In all cases, a high average particle yield of 99.63% was obtained. Smaller sizes (152.3 nm) can be obtained with the use of acetone as the desolvating agent and without any pretreatment. This is the first time that α-LA nanoparticles in the size range of 100 to 200 nm have been obtained. These nanoparticles, with an isoelectric point of 3.61, are very stable at pH values >4.8, based on their ζ-potential, although their antioxidant activity is weak. The use of the desolvating agent with the smallest polarity index (isopropanol) produced the largest particles (293.4 to 324.9 nm) in all cases. These results support the idea that controlling hydrophobic interactions is a means to control the size of α-LA nanoparticles. No effect of pretreatment on nanoparticle size could be detected. All types of nanoparticles were easily degraded by the proteolytic enzymes assayed.

Synthesis and characterization of polyvinyl alcohol/cellulose cryogels and their testing as carriers for a bioactive component

Novel physically cross-linked cryogels containing polyvinyl alcohol (PVA) and various amounts of microcrystalline cellulose were obtained by freezing/thawing technique. The main goal of this study was to improve the properties and the performances of the pure PVA cryogels. The morphological aspects of the cryogels were studied by scanning electron microscopy (SEM). The Fourier transform infrared spectroscopy (FT-IR) was used to reveal the presence of the interactions between the two polymers. Changes in crystallinity of the samples were confirmed by X-ray diffraction (XRD) and by FT-IR spectroscopy. The modification of the thermal behavior induced by cellulose was studied by thermogravimetry. Rheological analysis revealed higher values of storage modulus (G′) for the cryogels containing higher amounts of cellulose. The degree and rate of swelling were controlled by the presence of the natural polymer in the network. The potential application as bioactive compound carriers was tested, using vanillin as an active agent.

“Surface water” and “strong-bonded water” in cyclodextrins: a Karl Fischer titration approach

Cyclodextrins are some of the most used carriers for bioactive compounds (as host–guest complex) and many factors influence the association–dissociation of this complex, some of them being related to hydrophobicity. In the solid state, cyclodextrins contain two types of water molecules: “surface” water molecules (especially close to the crystal surface) and “strong-bonded” water molecules (especially from the cyclodextrin cavity), but the classification is hard to do, and the concentration of these water molecules are relatively difficult to estimate by simple methods.

Development of Drug Delivery Systems for Fish Larvae Reared in Aquaculture

3SparosLda – CRIA, UniversityofAlgarve, Portugal M marine fish larvae reared in aquaculture hatch withimmaturedigestive and immune systems, being extremely susceptible to diseases.Thus, sub-optimal rearing conditions are often associated with high larval mortalities, leading to high production losses. This work aimed to develop microencapsulated carriersof bioactive compounds to reduce disease susceptibility and increase fish larval survival. For this purpose, spraydrying and emulsification techniqueswere used to produce gelatin, chitosan, carrageenan and alginatemicrocarriers, where twomodel compounds were encapsulated: protein hydrolysateand a vitamins/minerals mixture, both with bioactive properties.Several techniques were used to characterise the carriers’ size, morphology and release profile. In addition, the first prototypes of alginate and carrageenanproduced by emulsification were tested for digestibility in Senegalese sole (Soleasenegalensis) larvae, a species targeted for aquaculture in Southern-European countries.Results showed that spraydrying produced delivery systems of adequate size (2-8 μm) fora subsequent inclusion infish larvae diets.Chitosan was electeda good matrix-forming material for these carriers, allowing40-70% of model drugs to be released according to aninitial controlledreleaseprofile.This is an important featureto prevent saturation of intestinal transporters in fish larvae. Water-in-oil emulsions produced microcarrierswithan adequate size for direct ingestion by fish larvae (50-250 μm). However, results also showed thatalginate and carrageenan carrierswere poorly digestedby sole larvae, suggesting that digestibility and release profile of chitosan and gelatin microcarriers produced by emulsion should be further investigated.

Solid lipid nanoparticles and nanoemulsions containing ceramides: Preparation and physicochemical characterization

Nanoemulsions (NEs) and solid lipid nanoparticles (SLNs) are widely used colloidal carriers for bioactive compounds. They are used in therapeutic, diagnostic, and cosmetic formulations. Ceramides are main components of the stratum corneum and are essential for the efficient barrier function. Their very high lipophilicity renders them difficult to incorporate in an acceptable formulation. The aim of this work was to investigate the possibility of using the benefits of nanotechnology in the efficient topical delivery of ceramides formulated as NEs or SLNs. The physicochemical characteristics of such carriers incorporating ceramides were investigated and their stability over time was assessed. Their morphology was examined under a scanning electron microscope and the interactions of their components were studied by differential scanning calorimetry. The results showed that the nanoemulsions can incorporate a high percentage (48.4% of total lipids by weight) of ceramides giving more homogeneous particle distributions of spherical-shaped nanoparticles and they maintained their characteristics over time. On the contrary, SLNs’ incorporation of ceramide higher than 10.8% of total lipids by weight led to the formation of rod-like nanoparticles deteriorating the homogeneity of the particle distribution, as depicted on the high polydispersity indexes of the corresponding formulations. The results demonstrate that NEs may be the more suitable carrier, compared to SLNs.

Affinity Chromatography as a Tool to Analyze Polyanion–Polycation Complexes: the Case of Poly(Llysine Citramide)–Poly(L-lysine) Systems

Artificial polymeric carriers for bioactive compounds, such as drugs and genes, are increasingly being reported in the literature. Most are polyelectrolytes aimed at being injected into body fluids that are composed of charged macromolecules (proteins, glycoproteins, poly(glycosamino glycane)s, polynucleotides, etc.). Many interactions can occur and lead to dramatic phenomena, such as polyelectrolyte complexation or substitution, cell aggregation and hemolysis. For the purpose of modeling and better understanding these interactions and their effects, a library of polyanions of the poly(L-lysine citramide)-type was interacted with the polycation poly(L-lysine) in aqueous media. Different fractions of complexes were generated by successive additions of aliquots of the polycation solution to the polyanion library solution by a titrating process. The two components, the polycation and the complex population of polyanions, were separated from the collected complex fractions by affinity chromatography and then analyzed by aqueous SEC. Molecular weight selectivity was shown, the high molecular weight polyanion macromolecules precipitated first, while complexes involving smaller molecules were found to remain in solution. The data show the potential of affinity chromatography for studying interpolyelectrolyte complexes and emphasizes the critical role that polydispersity can play when therapeutic charged macromolecules are injected into blood.

A Physico-chemical Approach of Polyanion-Polycation Interactions Aimed at Better Understanding the In Vivo Behaviour of Polyelectrolyte-based Drug Delivery and Gene Transfection

Polyanions and polycations are known to interact electrostatically and form soluble or insoluble polyelectrolyte complexes. Body fluids, blood and cells are composed of many polyelectrolytic systems such as proteins, glycoproteins, poly(glycosamino glycane)s, polynucleotides, etc. under physiological conditions. Nowadays synthetic polyelectrolytes are proposed as carriers of bioactive compounds, such as drugs and genes, and are thus to be injected into body fluids. For the sake of better understanding the complex behaviour of such artificial polyelectrolytic systems in the pool of natural polyelectrolytes forming living systems, interactions of bi- and multi-components mixtures of synthetic polyanions with the same synthetic polycation, namely poly[(dimethylaminoethyl) methacrylate], HCl, were investigated under the conditions imposed by physiological media, namely pH=7.4, ionic strength μ =0.15 and T =37°C. The selected artificial polyanions were the sodium salts of poly(acrylic acid), poly(methacrylic acid), poly (L -lysine citramide) and poly(styrene sulfonic acid) which have different acid strength, charge density and ionogenic group. The influence of ionic strength and pH on complex formation and stability was investigated by turbidimetry at λ =520 nm. Phase separation occurred regardless of ionic strength in the case of sodium polystyrene sulfonate. For the other polyanions, redissolution was observed at critical NaCl concentrations much higher than the physiological ionic strength. In the case of mixtures of two or three polyanions with the polycation, the complex formation appeared polyanion-selective at physiological ionic strength. Data are discussed with regard to phenomena that can occur in vivo.

Production of lipospheres as carriers for bioactive compounds

Aim of the present paper was to investigate the influence of preparation parameters on the production of lipospheres (LS) for drug delivery. LS composed of triglycerides and monoglycerides were alternatively produced by melt dispersion technique, solvent evaporation or w/o/w double emulsion method. The influence of preparation parameters, such as (a) type and amount of lipids, (b) presence and concentration of surfactants, (c) stirring speed and (d) type of stirrer was studied. In the case of LS prepared by melt dispersion, the use of a lipid composition of cetyl alcohol/cholesterol (2:1, w/w), a 5% (w/w) gelatin solution (50 bloom grades) and 1000 rpm stirring speed resulted in the production of spherical particles, with high percentage of recovery (82%, w/w) a mean diameter of 80 μm and a narrow size distribution. In the case of LS prepared by solvent evaporation, the best results in terms of LS morphology, recovery and size distribution were obtained by the use of a lipid composition of tristearin/monostearate (66:34, w/w), a 1% (w/w) PVA solution, a 750 rpm stirring speed and a 55 mm three-blade turbine rotor. The solvent evaporation method resulted in the production of LS characterised by a smaller size (20 μm mean diameter) but poor mechanical properties with respect to particles with the same composition obtained by the melt dispersion technique (170 μm mean diameter). The use of a combination of lipids and a methacrylic polymer (Eudragit RS 100) overcame this problem, resulting in the production of spherical particles, with a narrower size distribution and good mechanical properties. Two lipophilic drugs, such as retinyl acetate and progesterone, and one hydrophilic drug, sodium cromoglycate (SCG), were encapsulated in LS as model compounds. Lypophilic drugs displayed satisfactory encapsulation efficiencies (over 70% w/w), while SCG was very scarcely encapsulated (about 2% w/w). To solve this drawback, the use of a w/o/w double emulsion strategy was proposed, enabling to increase the encapsulation of SCG up to 50% w/w. Finally, in vitro drug release studies were performed, showing that all drugs were released in a control manner. In particular, the retinyl acetate release efficacy within the first 8 h was 27% of the total amount of the drug, while in the same period, the amount of progesterone released was 63%. With regard to SCG containing LS, the release of the drug was largely influenced by the type of stabiliser of the primary emulsion, in any case the SCG release reached the 100% of the total amount of drug after 5 h from the beginning of the experiment.