Impact of Spray-Drying on Biological Properties of Chitosan Matrices Supplemented with Antioxidant Fungal Extracts for Wine Applications.

Black aspergilli produce many bioactive compounds: enzymes, organic acids, and secondary metabolites. One such fungus, Aspergillus tubingensis G131, isolated from French Mediterranean vineyards, produces secondary metabolites with antioxidant properties that can be extracted with ethanol. In this study, crude antioxidant extracts obtained from A. tubingensis G131 cultures were encapsulated with two types of chitosan matrix. Spray-drying was used to obtain dried particles from a dispersion of fungal crude extracts in a solution of the coating agent chitosan. This process appeared to be an efficient method for obtaining a dry extract with antioxidant activity. Three types of fungal extracts, with different antioxidant capacities, were produced: two different concentrations of crude extract and a semi-purified extract. In this study, the chitosan matrices for encapsulation were chosen on the basis of their antimicrobial activities for wine applications. Classical low molecular weight chitosan was compared with NoBrett Inside® which is already used to prevent the development of Brettanomyces spp. in wine. The objective of this study was to confirm that both antioxidant (fungal extract) and antimicrobial (chitosan) properties were preserved after spray-drying. The combination of these two properties and the powder formulation of this entirely natural product would make it a good alternative to chemicals, such as sulfites, in the food and wine industries.

Spray-Dried Succinylated Soy Protein Microparticles for Oral Ibuprofen Delivery.

The potential value of succinylated soy protein (SPS) as a wall material for the encapsulation of ibuprofen (IBU), a model hydrophobic drug, by spray-drying was investigated. A succinylation rate of 93% was obtained for soy protein isolate, with a molar ratio of 1/1.5 (NH2/succinic anhydride). The solubility profile at 37°C showed that this chemical modification decreased the solubility of the protein below its isoelectric point, whereas solubility increased in alkaline conditions. Various SPS/IBU ratios (90/10, 80/20, and 60/40) were studied and compared with the same ratio of soy protein isolate (SPI/IBU). High encapsulation efficiency was achieved (91-95%). Microparticles were spherical and between 4 and 8 µm in diameter. The spray-drying of protein/IBU solutions appeared to be beneficial, as it resulted in an amorphous solid dispersion of IBU within the microparticles, coupled with an increase in the thermal stability of IBU. In vitro release was evaluated in acidic (pH 1.2 in the presence of pepsin) and neutral (pH 6.8) conditions similar to those in the gastrointestinal (GI) tract. IBU was released significantly more slowly at pH 1.2, for both proteins. However, this slowing was particularly marked for SPS, for which rapid (within 2 h) and complete release was observed at pH 6.8. These results validate the hypothesis that SPS is suitable for use as a coating material for hydrophobic active pharmaceutical ingredients (APIs) due to its pH sensitivity, which should delay IBU release in the gastrointestinal tract.

Soy Protein Microparticles for Enhanced Oral Ibuprofen Delivery: Preparation, Characterization, and In Vitro Release Evaluation.

The objective of this work was to evaluate soy protein isolate (SPI) and acylated soy protein (SPA) as spray-drying encapsulation carriers for oral pharmaceutical applications. SPI acylation was performed by the Schotten-Baumann reaction. SPA, with an acylation rate of 41%, displayed a decrease in solubility in acidic conditions, whereas its solubility was unaffected by basic conditions. The drug encapsulation capacities of both SPI and SPA were tested with ibuprofen (IBU) as a model poorly soluble drug. IBU-SPI and IBU-SPA particles were obtained by spray-drying under eco-friendly conditions. Yields of 70 to 87% and microencapsulation efficiencies exceeding 80% were attained for an IBU content of 20 to 40% w/w, confirming the excellent microencapsulation properties of SPI and the suitability of the chemical modification. The in vitro release kinetics of IBU were studied in simulated gastrointestinal conditions (pH 1.2 and pH 6.8, 37°C). pH-sensitive release patterns were observed, with an optimized low rate of release in simulated gastric fluid for SPA formulations, and a rapid and complete release in simulated intestinal fluid for both formulations, due to the optimal pattern of pH-dependent solubility for SPA and the molecular dispersion of IBU in soy protein. These results demonstrate that SPI and SPA are relevant for the development of pH-sensitive drug delivery systems for the oral route.

Interaction of substituted hexose analogues with the Trypanosoma brucei hexose transporter.

Glucose metabolism is essential for survival of bloodstream form Trypanosoma brucei subspecies which cause human African trypanosomiasis (sleeping sickness). Hexose analogues may represent good compounds to inhibit glucose metabolism in these cells. Delivery of such compounds to the parasite is a major consideration in drug development. A series of D-glucose and D-fructose analogues were developed to explore the limits of the structure-activity relationship of the THT1 hexose transporter of bloodstream form African trypanosomes, a portal that might be exploited for drug uptake. D-glucose analogues with substituents at the C2 and C6 position continued to interact with the exofacial hexose binding site of the transporter. There was a limit to the size at C6 which still permitted recognition, although compounds carrying large groups at position C2 were still recognised. However, radiolabelled N-acetyl-D-[1-14C] glucosamine was not internalised by trypanosomes, in spite of the ability of this compound to inhibit glucose uptake, indicating that there is a limit to the size of C2 substituent that allows translocation. Addition of an alkylating group (bromoacetyl) at position C2 in the D-glucose series and at position 6 in the D-fructose set, created two analogues which interact with the transporter and kill trypanosomes in vitro. This indicates that inhibition of the transporter may be a good means of killing trypanosomes.