Cristina M. Sabliov

Synthesis and characterization of PLGA nanoparticles

Poly(lactide-co-glycolide) (PLGA) nanoparticles of different physical characteristics (size, size distribution, morphology, zeta potential) can be synthesized by controlling the parameters specific to the synthesis method employed. The aim of this review is to clearly, quantitatively and comprehensively describe the top–down synthesis techniques available for PLGA nanoparticle formation, as well as the techniques commonly used for nanoparticle characterization. Many examples are discussed in detail to provide the reader with an extensive knowledge base on the important parameters specific to the synthesis method described and ways in which these parameters can be manipulated to control the nanoparticle physical characteristics.

Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release

An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped α-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of α-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of α-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% α-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the α-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% α-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% α-tocopherol theoretical loading (34% released in the first hour).

Continuous microwave-assisted isoflavone extraction system: Design and performance evaluation

The purpose of this research was to design, test, and optimize a continuous microwave extraction method using temperature and residence time during and after microwave exposure as optimizing parameters for extraction of major isoflavones (genistin, genistein, daidzin, and daidzein) from soy flour. The extraction yield of four isoflavones at different heating temperatures (55 and 73 degrees C) and extraction times (0, 4, 8, 12, and 16 min) were investigated and compared with yields provided by a conventional solvent extraction method. The microwave prototype consisted of multiple, commercially available, batch-type, house-hold microwave units placed on top of each other in series to impart a continuous operation. The optimum parameters for microwave-assisted extraction of isoflavones were 73 degrees C for 8 min using a 3:1 ethanol-to soy flour ratio. At these parameters, the total yield of isoflavones extracted doubled, while the amount of oil extracted was 12%. Continuous microwave-assisted solvent extraction is a viable method for extraction of soybean isoflavones at relatively short residence times and high throughput.

Engineered Nanoscale Food Ingredients: Evaluation of Current Knowledge on Material Characteristics Relevant to Uptake from the Gastrointestinal Tract

The NanoRelease Food Additive project developed a catalog to identify potential engineered nanomaterials (ENMs) used as ingredients, using various food-related databases. To avoid ongoing debate on defining the term nanomaterial, NanoRelease did not use any specific definition other than the ingredient is not naturally part of the food chain, and its dimensions are measured in the nanoscale. Potential nanomaterials were categorized based on physical similarity; analysis indicated that the range of ENMs declared as being in the food chain was limited. Much of the catalogs information was obtained from product labeling, likely resulting in both underreporting (inconsistent or absent requirements for labeling) and/or overreporting (inability to validate entries, or the term nano was used, although no ENM material was present). Three categories of ingredients were identified: emulsions, dispersions, and their water-soluble powdered preparations (including lipid-based structures); solid encapsulates (solid structures containing an active material); and metallic or other inorganic particles. Although much is known regarding the physical/chemical properties for these ingredient categories, it is critical to understand whether these properties undergo changes following their interaction with food matrices during preparation and storage. It is also important to determine whether free ENMs are likely to be present within the gastrointestinal tract and whether uptake of ENMs may occur in their nanoform physical state. A practical decision-making scheme was developed to help manage testing requirements.

Nanodelivery of Bioactive Components for Food Applications: Types of Delivery Systems, Properties, and Their Effect on ADME Profiles and Toxicity of Nanoparticles

Food bioactives are known to prevent aging, cancer, and other diseases for an overall improved health of the consumer. Nanodelivery provides a means to control stability, solubility, and bioavailability, and also provides controlled release of food bioactives. There are two main types of nanodelivery systems, liquid and solid. Liquid nanodelivery systems include nanoemulsions, nanoliposomes, and nanopolymersomes. Solid nanodelivery systems include nanocrystals, lipid nanoparticles, and polymeric nanoparticles. Each type of nanodelivery system offers distinct benefits depending on the compatibility of nanoparticle properties with the properties of the bioactive and the desired application. Physicochemical properties of nanoparticles such as size, charge, hydrophobicity, and targeting molecules affect the absorption, distribution, metabolism, and excretion (ADME) of nanodelivery systems. The fate of the bioactive depends on its physicochemical properties and the location of its release. The safety of nanodelivery systems for use in food applications is largely unknown. Toxicological studies consisting of a combination of in silico, in vitro, and in vivo studies are needed to reveal the safety of nanodelivery systems for successful applications in food and agriculture.

Human adipose-derived stem cells and three-dimensional scaffold constructs: A review of the biomaterials and models currently used for bone regeneration †

In the past decade, substantial strides have been taken toward the use of human adipose-derived stromal/stem cells (hASC) in the regeneration of bone. Since the discovery of the hASC osteogenic potential, many models have combined hASC with biodegradable scaffold materials. In general, rats and immunodeficient (nude) mice models for nonweight bearing bone formation have led the way to assess hASC osteogenic potential in vivo. The goal of this review is to present an overview of the recent literature describing hASC osteogenesis in conjunction with three-dimensional scaffolds for bone regeneration.

Ca2+ Cross-Linked Alginic Acid Nanoparticles for Solubilization of Lipophilic Natural Colorants

The increased tendency toward healthy lifestyles has promoted natural food ingredients to the detriment of synthetic components of food products. The trend followed into the colorant arena, with consumers worried about potential health problems associated with synthetic colorants and demanding food products that use natural pigments. The goal of this study was to entrap a lipophilic natural pigment (beta-carotene) in a water-soluble matrix made of Ca(2+) cross-linked alginic acid, to allow its use as a colorant in water-based foods. The effects of different synthesis parameters such as type of solvent, alginic acid concentration, and calcium chloride concentration on nanoparticle characteristics (i.e., size, zeta potential, and morphology) were evaluated. The particle stability was assessed by measuring aggregation against pH, oxidation, and particle precipitation as a function of time. The particle synthesized measured 120-180 nm when formed with chloroform and 500-950 nm when synthesized with ethyl acetate. The particles were negatively charged (-70 to -80 mV zeta potential) and were stable at pH values ranging from 3 to 7. The presence of calcium was prevalent on the particles, indicating that the divalent ions were responsible for cross-linking lecithin with alginic acid and forming the matrix around the beta-carotene pockets. The addition of calcium increased nanoparticle density and improved beta-carotene protection against oxidation. It is concluded that the method proposed herein was capable of forming water-soluble nanoparticles with entrapped beta-carotene of controlled functionality, as a result of the type of solvent and the amounts of alginate and Ca(2+) used.

Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles

Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl-glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl-leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml( - 1) TQ for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 +/- 0.002 mg ml( - 1)) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 +/- 5.6% after 96 h.

Extraction of Antioxidants from Wheat Bran Using Conventional Solvent and Microwave-Assisted Methods

ABSTRACT Total phenolic and tocopherol contents and free radical scavenging capability of wheat bran extracted using conventional and microwave-assisted solvent extraction methods were studied. Three different solvents (methanol, acetone, and hexane) were used in the conventional solvent extraction. Methanol was the most effective solvent, producing higher extraction yield (4.86%), total phenolic compound content (241.3 μg of catechin equivalent/g of wheat bran), and free radical scavenging capability (0.042 μmol of trolox equivalent/g of wheat bran) than either acetone or hexane. However, there was no significant difference in the total tocopherol contents (13.6–14.8 μg/g of wheat bran) among the three different solvent extraction methods. Microwave-assisted solvent extraction using methanol significantly increased the total phenolic compound content to 467.5 and 489.5 μg of catechin equivalent; total tocopherol content to 18.7 and 19.5 μg; and free radical scavenging capability to 0.064 and 0.072 μmol o...

Chitosan/PLGA particles for controlled release of α-tocopherol in the GI tract via oral administration

AIM The physiochemical properties, controlled release characteristics, stability and cellular uptake of chitosan (Chi)/poly(D,L-lactide-co-glycolide) (PGLA) and PLGA particles with entrapped α-tocopherol were investigated to understand the behavior of these nanoparticles in the GI tract. MATERIALS & METHODS Chi/PLGA and PLGA particles stabilized by lecithin were synthesized and fully characterized for oral gastrointestinal delivery via transmission electron microscopy, dynamic light scattering, high-performance liquid chromatography and fluorescence microscopy. RESULTS Particle stability was pH- and system-dependent. In vitro release profiles showed a higher percentage of drug released in the intestinal domain by Chi/PLGA as opposed to the PLGA nanoparticles. Fluorescent counterparts of these particles were confirmed to associate with the surface of the intestinal villi, and penetrate deep in the endothelial lining of rabbit intestinal explants, indicating uptake. CONCLUSION In vitro and ex vivo results showed that PLGA and Chi/PLGA nanoparticles were efficiently taken up by the GI tract and could be optimized to deliver α-tocopherol to the intestine and improve its bioavailability.