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.