Cancer is the second cause of death worldwide, exceeded only by cardiovascular diseases. The prevalent treatment currently used against metastatic cancer is chemotherapy. Among the most studied drugs that inhibit neoplastic cells from acquiring unlimited replicative ability (a hallmark of cancer) are the taxanes. They operate via a unique mol. mechanism affecting mitosis. In this review, we show this mechanism for one of them, paclitaxel, and for other (non-taxanes) anti-mitotic drugs. However, the use of paclitaxel is seriously limited (its bioavailability is \textless10%) due to several long-standing challenges: its poor water soly. (0.3 $μ$g/mL), its being a substrate for the efflux multidrug transporter P-gp, and, in the case of oral delivery, its first-pass metab. by certain enzymes. Adequate delivery methods are therefore required to enhance the anti-tumor activity of paclitaxel. Thus, we have also reviewed drug delivery strategies in light of the various phys., chem., and enzymic obstacles facing the (esp. oral) delivery of drugs in general and paclitaxel in particular. Among the powerful and versatile platforms that have been developed and achieved unprecedented opportunities as drug carriers, microemulsions might have great potential for this aim. This is due to properties such as thermodn. stability (leading to long shelf-life), increased drug solubilization, and ease of prepn. and administration. In this review, we define microemulsions and nanoemulsions, analyze their pertinent properties, and review the results of several drug delivery carriers based on these systems. [on SciFinder(R)]

Microemulsions (MEs) have gained increasing interest as carriers of hydrophobic bioactives in the last decades. However, it is still difficult to control the uptake and the release of bioactives directly extd. from plants. In this study, modified ME nanodroplets (nano-sized self-assembled liqs., NSSLs) were employed as extn. medium of gossypol, a toxic component of cottonseed. Loading was performed using both pure gossypol, and gossypol obtained by extn. from cottonseed. We achieved two goals: (i) remove gossypol from cottonseed to obtain cotton-oil free of gossypol; and (ii) ext. gossypol directly into a nano-delivery vehicle for biomedical purposes. Structural and dynamical information on the unloaded and gossypol-loaded NSSL systems were obtained by self-diffusion NMR, SD-NMR, and spin-probe ESR (EPR) studies. The results showed that NSSL formed fluid water-in-oil (W/O) nano domains at the lowest water contents; a more viscous bicontinuous structure at comparable oil and water contents, and, finally, oil-in-water (O/W, micellar-like) at the higher concn. of water. These micellar-like structures were more fluid at the external hydrated surface, as demonstrated by SD-NMR, while the lipidic region tested by EPR revealed an increasing packing. In all these structures, gossypol mainly localized in the lipophilic region close to the water interface. Overall, SD-NMR and EPR provided complementary information, helping to clarify the structural properties of NSSLs formed at different water contents and their ability to incorporate gossypol also directly from cottonseed-NSSL mixts. [on SciFinder(R)]

Microemulsions are widely studied as potential ocular drug delivery vehicles. In the present study we show the versatility of possible use microemulsions as ocular delivery vehicle. The ME is loaded with a hydrophilic drug, riboflavin phosphate (RFP) and a lipophilic, docosahexaenoic acid in triglyceride form (TG-DHA), each sep. These drugs treat keratoconus and dry eye syndrome, resp. The advantage of using ME loaded with RFP is in overcoming eye epithelium debridement during collagen crosslinking therapy for treatment of keratoconus. ME loaded with lipophilic TG-DHA provides convenient dosage in liq. aq. form of administration of highly lipophilic TG-DHA, which is known as a protective mol. in dry eye syndrome. The capability of RFP-loaded MEs was demonstrated in terms of improvement of biomech. strength of the rabbit cornea, as a result of successful penetration of RFP through the intact epithelium. TG-DHA-loaded microemulsion applied topically onto an eye with induced dry eye syndrome showed the significant relief of the dry eye condition. [on SciFinder(R)]

Pharmaceutical applications of microemulsions (MEs) as drug delivery vehicles are recently gaining scientific and practical interests. Most MEs are able to solubilize bioactive molecules, but, at present, they cannot guarantee either controlled release of the drugs or significant advantage in the bioavailability of the bioactives. This study proposes to incorporate the modified ME structures, or nanodomains, into a natural polymeric film, to be used as a stable and capacious reservoir of drug-loaded nanodomains. These nanodomainloaded films may release the nanodroplets along with the drug molecules in a slow and controlled way. Gellan gum, an anionic polysaccharide, was used in aqueous solution as the film former, and curcumin, hydrophobic polyphenol, served as the guest molecule in the loaded systems. Films were prepared by using empty and curcumin-loaded MEs. It is imperative to verify the persistence of the ME structure upon the dissolution of the film mimicking its behavior when in contact with a human physiological aqueous environment via reaching the cell membranes. For this purpose, the films were dissolved, and the reconstituted ME structure was compared with the ME structure before film formation. Characterization of these structures, before and after dissolution, was achieved using electron paramagnetic resonance (EPR) and self-diffusion nuclear magnetic resonance (SD-NMR) techniques. Specific spin probes were inserted in the system, and a computer-aided analysis of the EPR spectra was performed to provide information on nanodomain microstructure assemblies. In addition, the SD-NMR profile of each component was analyzed to extract information on the diffusivity of the ME components before film formation and after ME reconstitution. The EPR and SD-NMR results were in good agreement to each other. The most important finding was that, after film dissolution, the ME nanodomains were reversibly and spontaneously reformed. It was also found that the film did not perturb the ME-nanodomain structure embedded in it. The film remained transparent and the bioactive curcumin was easily solubilized into the ME-droplet/water interface even after film dissolution. The combined techniques confirmed that the film constituted by bioactive-loaded MEs can serve as novel drug delivery vehicles.

עד לפני כמה עשורים נחשבו השמנים הצמחיים לקבוצה הומוגנית, שהמשותף לה הוא היותם נוזליים בטמפרטורת החדר וממקור צמחי. צלילה לתוך עולם השמנים מעידה על כך שרב השונה והמיוחד על המשותף, הן בתכונות הכימיות והפיסיקליות, בתהליכי ההפקה, בשימושים בבישול ובתעשייה, והן בהשפעות הבריאותיות הנובעות מכל אלה. המאמר מתייחס להגדרות, הבדלים ומקורות של שמנים ושומנים, המקורות להם, שמנים בכבישה קרה ושמנים מיוחדים במזון וכתוספי תזונה.

This study presents a directly aggregated pseudo-ternary system. The three apexes of the investigated system represent a surfactant phase [Tween 80:propylene glycol (9:1 wt ratio)], an oil phase [isopropyl myristate:benzyl alc. (7.5:2.5 wt ratio)], and water. Within the pseudo-ternary system, water diln. line, termed N91 (90 wt% surfactant phase and 10 wt% oil phase), was found to represent transparent and thermodynamically stable compns. from conc. to high water diln. (>95 wt% water). Despite that the system was found to be directly aggregated, diln. line N91 exhibited classical L2→L1 phase inversion characteristics (at 39 wt% water). To explain this phenomenon, a novel structural interpretation regarding the obsd. inversion as an obstruction of the bidiscontinuous phase, consisting of oil and water-segregated domains, is proposed. The evaluation of diln. line N91 was based on elec. cond., SAXS, SD-NMR, rheometry, DSC and cryo-TEM. The structural transitions along water diln. line N91 were found to be as follows: 'pseudo L1' (pseudo direct surfactant-oil aggregates) → bi-discontinuous structure (of which partial is a hexagonal H1 mesophase) → L1. We concluded that the high concn. of low CPP (crit. packing parameter) surfactant plays a major role in detg. the system's geometry throughout the water diln. line. As a result, the proposed interpretation of the structural inversion obsd. along diln. line N91 differs from the classical U-type inversion interpretation (L2 →bicontinuous →L1). [on SciFinder(R)]

In the present study we aimed to control insulin release from the reverse hexagonal (H-II) mesophase using Thermomyces lanuginosa lipase (TLL) in the environment (outer TLL) or within the H-II cylinders (inner TLL). Two insulin-loaded systems differing by the presence (or absence) of phosphatidylcholine (PC) were examined. In general, incorporation of PC into the H-II interface (without TLL) increased insulin release, as a more cooperative system was formed. Addition of TLL to the systems' environments resulted in lipolysis of the H-II structure. In the absence of PC, the lipolysis was more dominant and led to a significant increase in insulin release (50% after 8 h). However, the presence of PC stabilized the interface, hindering the lipolysis, and therefore no impact on the release profile was detected during the first 8 h. Entrapment of TLL within the H-II cylinders (with and without PC) drastically increased insulin release in both systems up to 100%. In the presence of PC insulin released faster and the structure was more stable. Consequently, the presence of lipases (inner or outer) both enhanced the destruction of the carrier, and provided sustained release of the entrapped insulin. (C) 2017 Elsevier B.V. All rights reserved.

The present disclosure provides cannabinoid-loaded formulations, as well as processes for their prepn. [on SciFinder(R)]

The present disclosure provides methods for extn. of various agents, e.g. active agent, from a plant source, specifically with the use of extn. formulations which are based on micellar liq. systems. [on SciFinder(R)]

The present disclosure provides methods for selective extn. of cannabinoids, for example cannabidiol (CBD), from a plant source, by using tailored extn. media. [on SciFinder(R)]

The disclosure concerns viscous or gelled delivery systems based on oily nano-domains dispersed in a viscosified/gelled continuous aq. phase, and suitable for prolonged and/or sustained topical delivery of various active compds. [on SciFinder(R)]

Dendrimer nanostructures are of eminent interest in biomedical applications because of their uniform and well-defined molecular size and shape, and their ability to cross cell membranes and reduce the risk of premature clearance from the human body. Dendrimers perform as gene and drug carriers and have also shown significant therapeutic properties for treating cancer and neurodegenerative diseases. A complex drug delivery system, based on a dendrimer solubilized in the aqueous core of a water-in-oil (W/O) microemulsion (ME) along with the drug may combine the advantages of both dendrimers and MEs to provide better control of drug release. We propose a new microemulsion composed of drug-permitted surfactants and dendrimer that can be used as a potential controlled drug delivery nanosystem. The influence of second generation poly(propyleneimine) (PPI-G2) dendrimer; solubilized in (W/O) ME with a capacity of up to 25 wt% PPI-G2 at various pHs; and their interactions with the surfactant phosphatidylcholine (PC), cosurfactant (butanol), and water was studied. SAXS and EPR measurements indicated that increasing PPI-G2 concentration reduces droplet curvature and increases droplet size thus increasing macro-(SAXS) and micro-(EPR) order degree. Furthermore, SD-NMR and ATR-FTIR show stronger interactions between PPI-G2 and water molecules at the expense of PC and butanol headgroups hydration, which increases microviscosity (EPR). PPI-G2's effect is somewhat opposite to the increasing water phase effect, thus reducing the amount of free water (DSC) and slowing the mobility of all ME components (SD-NMR).[on SciFinder (R)]

The present work reports on the prepn. and characterization of progesterone-loaded reverse hexagonal (HII) mesophase based on a glycerol monooleate (GMO)/tricaprylin (TAG)/water mixt. for transdermal application. Several compns. into which progesterone was quant. solubilized were selected and used in the present study in order to evaluate the effect of the hormone on structural transitions and characteristics. A GMO/TAG of 90:1 wt ratio with 20 wt% water was found to form HII mesophases with relative high solubilization capacity of 4 wt% progesterone and a shelf life of over one year. The structures were identified by cross-polarized light microscopy (CPLM). Structural confirmations were obtained from small-angle X-ray scattering (SAXS) measurements. The hormone is solubilized at the interface of the HII mesophase as confirmed by SAXS, rheol., FTIR, and DSC. The progesterone, which is loaded onto reverse hexagonal cylinders, leads to strengthening the hydrogen bonding and to better packing of the HII mesophase, suggesting that progesterone is a kosmotropic agent. The reverse hexagonal mesophase seems to be a promising carrier for solubilization of progesterone. [on SciFinder(R)]

Insulin loading into the HII mesophases was examd. as a function of its concn., with addn. of glycerol as a cosolvent and with addn. of phosphatidylcholine (PC) as a structural stabilizer. The structural properties, the mol. interactions, the viscoelastic properties, and the dynamic behavior were investigated by SAXS, ATR-FTIR, and rheol. measurements. Insulin release was then monitored and analyzed. Insulin incorporation into the HII systems shrank the cylinders as it competed with the lipids in water-bonding. Insulin interrupted the interface while increasing $\tau$max and creating a more solid-like response. Upon addn. of PC, cooperative flow behavior was detected, which is probably the reason for increase in insulin cumulative release from 28% to 52% after 300 min. In the presence of glycerol, the system was less cooperative but insulin was more compactly folded, resulting in a slight improvement in insulin release (up to 6%). Addn. of both PC and glycerol caused the max. release (55%). The addn. of additives into the HII system demonstrates how structural modifications can improve insulin release, and influence future design of encapsulated drug delivery systems. [on SciFinder(R)]

NMR chromatog. is a promising and superior alternative to NMR spectroscopy for analyzing mixts. since it simultaneously separates the spectra of the compds. and supplies information about their structure. This implies that there is no need for extn., purifn. or synthesis of stds., that are expensive, time consuming and usually impractical. The main aim of NMR chromatog. is to increase the differences in the diffusivities of different analytes in a mixt., allowing them to be more easily and reliably identified. The selection of surfactants and other components of microemulsions for the best performance as NMR chromatog. media was studied. Attention was focused on the selection of the proper cosolvent in three types of water-dilutable microemulsions: two anionic (deuterated ionic and the previously published fluorinated ionic) and one nonionic (undeuterated Tween-based). The diffusivities of several analytes are compared. The study also examines the effect of diln. and dets. the best compns. for the NMR chromatog. performance. For the anionic microemulsions, 1-butanol was found to be the most promising cosurfactant in the deuterated system 1-butanol-d10:toluene-d8:SDS-d25 in a 6:3:1 wt.-ratio dild. by D2O. This compn., dild. with a 85 wt% D2O, formed a microemulsion that was even stable at relatively elevated temps. (70 °C) and can serve as good medium for chromatog. NMR. Another possibility that was studied consists of nonionic-based microemulsions of iso-Pr alc. (IPA) in IPA:toluene:Tween 20 that could also be easily dild. indefinitely with water. IPA was found to be a very efficient cosurfactant at resolving diffusivities of all the components. However, the lack of availability of deuterated Tween makes it impractical for use as an NMR chromatog. formulation. [on SciFinder(R)]

Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compds. are water-insol. and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future. The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water diln. line using ESR and pulsed-gradient spin-echo NMR along with other anal. techniques. The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water diln. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5 wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants. In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5 wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface. [on SciFinder(R)]

Double emulsions are emulsions in which an emulsion [water/oil (W/O) or oil/water] is dispersed in a continuous phase (water or oil, resp.), producing W/O/W or O/W/O. These systems have considerable potential in food systems, cosmetics, and pharmaceuticals. This entry reviews some studies and discusses the different approaches that have been introduced. The studies provide better understanding of the stabilizing mechanisms and pathways and a better control of the release patterns from double emulsions. [on SciFinder(R)]

In microemulsions, changes in droplet size and shape and possible transformations occur under various conditions. They are difficult to characterize by most analytical tools because of their nano-sized structure and dynamic nature. Several methods are usually combined to obtain reliable information, guiding the scientist in understanding their physical behavior. We felt that there is a need for a technique that complements those in use today in order to provide more information on the microemulsion behavior, mainly as a function of dilution with water. The improvement of NMR chemical shift measurements independent of bulk magnetization effects makes it possible to study the very weak intermolecular chemical shift effects. In the present study, we used NMR high resolution magic angle spinning to measure the chemical shift very accurately, free of bulk magnetization effects. The chemical shift of microemulsion components is measured as a function of the water content in order to validate the method in an interesting and promising, U-type dilutable microemulsion, which had been previously studied by a variety of techniques. Phase transition points of the microemulsion (O/W, bicontinuous, W/O) and changes in droplet shape were successfully detected using high-accuracy chemical shift measurements. We analyzed the results and found them to be compatible with the previous studies, paving the way for high-accuracy chemical shifts to be used for the study of other microemulsion systems. We detected two transition points along the water dilution line of the concentrate (reverse micelles) corresponding to the transition from swollen W/O nano-droplets to bicontinuous to the O/W droplets along with the changes in the droplets' sizes and shapes. The method seems to be in excellent agreement with other previously studied techniques and shows the advantage of this easy and valid technique. (C) 2014 Elsevier Inc. All rights reserved.

Cholesterol (CH) is a vital mol. for mammalian life. It functions as a precursor for a variety of biol. active mols. and as a moderator of membrane mobility, and has many other essential functions. However, a high blood CH level can cause development of cardiovascular diseases. The soln. for high CH level is an intake of CH-lowering drugs such as statins. Another option for lowering excess CH is intake of phytosterols (PS) as a nutraceutical, which reduces CH absorption in mammals. PS are sterols synthesized only in plants and are structurally similar to CH but with an extra hydrophobic carbon chain at the C-24 position. PS and CH both have low soly. in oil and even lower soly. in water. To improve the efficiency of PS in lowering CH level, it is important to develop suitable vehicles that will improve their solubilization and absorption. In this entry, we examine sterol-solubilization vehicles, which include micelles, emulsions, microemulsions, and bile salt (BS) systems. The discussion focuses on the solubilization capacity (SC) of the vehicles and their effect on the extent of CH absorption/inhibition. It can be concluded that the solubilized PS in these various vehicles enables a significant decrease in CH absorption in comparison to the intake of PS in its solid form. In addn., we shall review the competitive solubilization of CH and PS in microemulsion systems to understand the competitive solubilization mechanism, which has been proposed as one of the mechanisms for PS activity as a CH-lowering agent. [on SciFinder(R)]