Encapsulation systems for the delivery of hydrophilic nutraceuticals: Food application.

Increased health risk associated with the sedentary life style is forcing the food manufacturers to look for food products with specific or general health benefits e.g. beverages enriched with nutraceuticals like catechin, curcumin rutin. Compounds like polyphenols, flavonoids, vitamins are the good choice of bioactive compounds that can be used to fortify the food products to enhance their functionality. However due to low stability and bioavailability of these bioactives (both hydrophobic and hydrophilic) within the heterogeneous food microstructure and in the Gastro Intestinal Tract (GIT), it becomes extremely difficult to pass on the real health benefits to the consumers. Recent developments in the application of nano-delivery systems for food product development is proving to be a game changer which has raised the expectations of the researchers, food manufacturers and consumers regarding possibility of enhancing the functionality of bioactives within the fortified food products. In this direction, nano/micro delivery systems using lipids, surfactants and other materials (carbohydrates, polymers, complexes, protein) have been fabricated to stabilize and enhance the biological activity of the bioactive compounds. In the present review, current status of the various delivery systems that are used for the delivery of hydrophilic bioactives and future prospects for using other delivery systems that have been not completely explored for the delivery of hydrophilic bioactives e.g. niosomes; bilosomes, cubosomes are discussed.

Amorphous nano-curcumin stabilized oil in water emulsion: Physico chemical characterization.

Particle characteristics e.g. size and polymorphism are known to significantly affect the Pickering ability of the solid particles by influencing their interaction at the oil and water (O/W) interface. In this study, nano-sized amorphous curcumin particles were fabricated using nanonization technology to use them as Pickering particles. After nanonization, native crystalline curcumin particles were converted into amorphous, nanosized particles of ∼220nm. Amorphous nature of the particle was evident from the decreased melting point from 177±1°C (native curcumin) to 146±3°C (nanonized curcumin) and enthalpy from 27±2J/g to 3.5±1J/g. Interfacial tension (IFT) studies have shown a decrease in IFT at the O/W interface from ∼27mN/m to ∼15mN/m in the presence of amorphous curcumin particles in water phase compared to crystalline curcumin particles. Curcumin stabilized O/W emulsion has an initial droplet size of ∼1.2µm and they were stable for 30days at 4°C.

Development of artemether and lumefantrine co-loaded nanostructured lipid carriers: physicochemical characterization and in vivo antimalarial activity.

CONTEXT: Artemether and lumefantrine combination therapy is well-accepted for uncomplicated malaria treatment. However, the current available formulation has several pharmacokinetic mismatches such as drug degradation in gastrointestinal tract, erratic absorption, etc. Hence, need of the hour is the injectable formulation, which can overcome the pharmacokinetic mismatch associated with current available formulation in the market. OBJECTIVE: To fabricate artemether and lumefantrine co-loaded injectable nanostructured lipid carriers (NLCs) formulation. MATERIALS AND METHODS: Artemether and lumefantrine co-loaded NLCs were fabricated using homogenization followed by ultra-sonication method. Fabricated NLCs were evalauated for their physicochemical characteristics, and suitability of the formulation for malaria treatment was evaluated using in vivo animal model (Plasmodium berghei-infected mice). Results, discussion and conclusion: Artemether and lumefantrine co-loaded NLCs had a hydrodynamic diameter of ∼ 145 nm with the surface charge of -66 mV. Due to the lipophilic nature of both antimalarial drugs, both single drugs-loaded and co-loaded NLCs have shown high encapsulation efficiency, which is 84% for artemether and 79% for lumefantrine. In vitro drug release study has shown a biphasic drug release pattern, which has shown 63% artemether release and 45% of lumefantrine release over a time period of 30 h. Plasmodium berghei-infected mice treated with artemether and lumefantrine co-loaded NLCs showed better antimalarial activity with respect to parasitemia progression and survivability period.

Fabrication of amorphous curcumin nanosuspensions using ß-lactoglobulin to enhance solubility, stability, and bioavailability.

Curcumin has low aqueous stability and solubility in its native form. It also has a low bioavailability which presents a major barrier to its use in fortifying food products. The aim of this work was to reduce the size of curcumin crystals to the nanoscale and subsequently stabilize them in an amorphous form. To this end, amorphous curcumin nanosuspensions were fabricated using the antisolvent precipitation method with ß-lactoglobulin (ß-lg) as a stabilizer. The resulting amorphous curcumin nanosuspensions were in the size range of 150-175 nm with unimodal size distribution. The curcumin particles were amorphous and were molecularly dispersed within the ß-lg as confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. The solubility of the amorphous curcumin nanosuspension was enhanced ∼35-fold due to the reduced size and lower crystallinity. Among the formulations, the amorphous curcumin nanosuspensions stabilized with ß-lg and prepared at pH 3.4 (ß-lg-cur 3.4), showed maximum aqueous stability which was >90% after 30 days. An in vitro study using Caco-2 cell lines showed a significant increase in curcumin bioavailability after stabilization with ß-lg.

Co-delivery of hydrophobic curcumin and hydrophilic catechin by a water-in-oil-in-water double emulsion.

Curcumin and catechin are naturally occurring phytochemicals with extreme sensitivity to oxidation and low bioavailability. We fabricated a water-in-oil-in-water (W/O/W) double emulsion encapsulating hydrophilic catechin and hydrophobic curcumin simultaneously. The co-loaded emulsion was fabricated using a two-step emulsification method, and its physicochemical properties were characterised. Volume-weighted mean size (d43) of emulsion droplets was ≈3.88 µm for blank emulsions, whereas it decreased to ≈2.8-3.0 µm for curcumin and/or catechin-loaded emulsions, which was attributed to their capacity to act as emulsifiers. High entrapment efficiency was observed for curcumin and/or catechin-loaded emulsions (88-97%). Encapsulation of catechin and curcumin within an emulsion increased their stability significantly in simulated gastrointestinal fluid, which resulted in a four-fold augmentation in their bioaccessibility compared to that of freely suspended curcumin and catechin solutions. Co-loading of curcumin and catechin did not have adverse effects on either compound's stability or bioaccessibility.

Effect of aqueous pH and electrolyte concentration on structure, stability and flow behavior of non-ionic surfactant based solid lipid nanoparticles.

The effects of pH and electrolyte concentration on the structure evolution, polymorphism, flow behavior and stability of solid lipid nanoparticles (SLNs), stabilized by the food-grade non-ionic surfactant Tween 80, were investigated. Development of a lipid crystal was governed by thermodynamically stable ß- and ß'-subunits and relative crystallinity decreased with increasing pH and electrolyte concentration. Aqueous stability and dispersibility increased with increasing pH and decreased with increasing electrolyte concentration. Flow behavior of the SLNs suspension was affected by the electrolyte concentration. However, the pH of the aqueous surfactant medium has not shown any effect on the flow behavior. From the results, it is clear that the pH and electrolyte concentration are among the potential factors which determines the stability and release properties of entrapped materials from SLNs.

Advances in nanomedicines for malaria treatment.

Malaria is an infectious disease that mainly affects children and pregnant women from tropical countries. The mortality rate of people infected with malaria per year is enormous and became a public health concern. The main factor that has contributed to the success of malaria proliferation is the increased number of drug resistant parasites. To counteract this trend, research has been done in nanotechnology and nanomedicine, for the development of new biocompatible systems capable of incorporating drugs, lowering the resistance progress, contributing for diagnosis, control and treatment of malaria by target delivery. In this review, we discussed the main problems associated with the spread of malaria and the most recent developments in nanomedicine for anti-malarial drug delivery.

Curcumin and genistein coloaded nanostructured lipid carriers: in vitro digestion and antiprostate cancer activity.

To increase the oral bioavailability of curcumin and genistein, we fabricated nanostructured lipid carriers (NLCs), and the impact of these carriers on bioaccessibility of curcumin and genistein was studied. Entrapment efficiency was more than 75% for curcumin and/or genistein-loaded NLCs. Solubility of curcumin and/or genistein in simulated intestinal medium (SIM) was >75% after encapsulating within NLCs which otherwise was <20%. Both curcumin and genistein have shown good stability (≥85%) in SIM and simulated gastric medium (SGM) up to 6 h. Coloading of curcumin and genistein had no adverse effect on solubility and stability of each molecule. Instead, coloading increased loading efficiency and the cell growth inhibition in prostate cancer cells. Collectively, these results have shown that coloaded lipid based carriers are promising vehicles for oral delivery of poorly bioaccessible molecules like curcumin and genistein.

Curcuminoids-loaded liposomes in combination with arteether protects against Plasmodium berghei infection in mice.

Curcuminoids are poorly water-soluble compounds with promising antimalarial activity. To overcome some of the drawbacks of curcuminoids, we explored the potential of liposomes for the intravenous delivery of curcuminoids in a model of mouse malaria. The curcuminoids-loaded liposomes were formulated from phosphatidylcholine (soy PC) by the thin-film hydration method. Antimalarial activity of curcuminoids-loaded liposomes alone and in combination with α/ß arteether when administered intravenously, was evaluated in Plasmodium berghei infected mice. Animals treated with curcuminoids-loaded liposomes showed lower parasitemia and higher survival when compared to control group (no treatment). Importantly, the combination therapy of curcuminoids-loaded liposomes (40 mg/kg body wt) along with α/ß arteether (30 mg/kg body wt) was able to not only cure infected mice but also prevented recrudescence. These data suggest that curcuminoids-loaded liposomes may show promise as a formulation for anti-malarial therapy.

Arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration: Pharmacokinetics, toxicological and in vivo anti-malarial activity.

Artemether-loaded lipid nanoparticles (ARM-LNP) composed of 5% (w/v) lipid mass were produced by a modified thin-film hydration method using glyceryl trimyristate (solid lipid) and soybean oil (as liquid lipid in a concentration ranging from 0 to 45% (w/v) with respect to the total lipid mass). The particles were loaded with 10% of the anti-malarial ARM and surface-tailored with a combination of non-ionic, cationic or anionic surfactants. ARM-LNP were further characterized for their mean particle size, zeta potential and encapsulation efficiency, reporting optimized values below 120nm (PI<0.250), -38mV and 97% (w/w), respectively. ARM-LNP composed of 45% soybean oil depicted a spherical-like shape by transmission electron microscopy and a biphasic release profile in phosphate buffer. Haemolytic activity was within the acceptable range (7%) revealing low toxicity risk of LNP for parenteral delivery of ARM. Biocompatibility was confirmed by hepato- and nephrotoxicity analyses. Histopathological analysis showed no significant histological changes in liver and kidney tissues in adult Swiss Albino mice treated with the selected formulations. In vivo anti-malarial activity of ARM was enhanced when formulated as LNP, in comparison to a conventional plain drug solution and to a marketed formulation which are currently in use to treat malaria patients.