Production of Margarines Rich in Unsaturated Fatty Acids Using Oxidative-stable Vitamin C-Loaded Oleogel.

Vitamin C (VC)-loaded oleogel (VCOG) with corn oil and monoglyceride stearate was used to replace lipid phase of margarine completely. The oxidative stability of VCOG was evaluated at 60±1°C in a lightproof oven for 18 days and the result showed that VCOG peroxide (> 6 days) and p-anisidine value (> 4 days) was significantly lower than that of bulk oil and VC-free oleogel (p < 0.05). Then, the margarine containing 79.70% VCOG (VCOGM) was in comparison with four commercial butter in sensory and physical characteristic. Results showed that firmness, solid fat content and trans fatty acid of VCOGM were in the lowest values while unsaturated fatty acid and adhesiveness of VCOGM was in the highest values. Furthermore, VCOGM presented the similar springiness, cohesiveness, gumminess, score appearance, texture, taste and overall impression to some/all commercial butters selected in this research (p > 0.05). These results implied that VC-loaded oleogel was an excellent alternative of lipid phase in margarine which confirmed by 55% "definitely buy" and 25% "try once-then decide".

A Novel Long-circulating DOX Liposome: Formulation and Pharmacokinetics Studies.

BACKGROUND: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDA-approved PEG-liposomes of DOX for the treatment of over 600,000 cancer patients, and it can overcome doxorubicin-induced cardiomyopathy and other side effects and prolong life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. OBJECTIVE: We intended to prepare a novel DOX liposome that was prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical application. METHODS: DOX liposomes were prepared using the combination of thin-film dispersion ultrasonic method and ammonium sulfate gradient method and the factors that influenced formulation quality were optimized. After formulation, particle size, entrapment efficiency, drug loading, stability, and pharmacokinetics were determined. RESULTS: DOX liposomes were near-spherical morphology with the average size of 90 nm and polydispersity index (PDI) of less than 0.30. The drug loading was up to 7.5%, and the entrapment efficiency was over 80%. The pharmacokinetic studies showed that free DOX could be easily removed and the blood concentration of free DOX group was significantly lower than that of DOX liposomes, which indicated that the novel DOX liposome had a certain sustainedrelease effect. CONCLUSION: In summary, DOX liposome is economical and easy-prepared with prolonged circulation time. Lay Summary: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDAapproved PEG-liposomes of DOX to treat over 600.000 cancer patients, overcoming doxorubicin- induced cardiomyopathy and other side effects and prolonging life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. We intend to prepare a novel DOX liposome prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical use. The novel DOX liposome is economical and easy-prepared with prolonged circulation time.

Structuring of sunflower oil by stearic acid derivatives: Experimental and molecular modelling studies.

Structuring of vegetable oils has potential application in food, pharmaceutical and cosmetic products. In this study, structuring effects of stearic acid derivatives on sunflower seed oil were systematically investigated by experimental and molecular simulation methods. Stearic acid (SA), 12-hydroxy stearic acid (HSA) and 2-hydroxyethyl stearate (HES) were able to structure sunflower seed oil, among which the structuring ability of HES was reported for the first time. The oleogel formed with HSA exhibited good mechanical properties (such as hardness, fracturability, adhesiveness, chewiness and storage modulus), which coincided with its highest solid fat content and degree of crystallinity. Oleogels containing SA and HES showed similar mechanical properties. Both the molecular dynamics (MD) simulation and independent gradient model (IGM) confirmed that the HSA dimer possessed the strongest interaction during the self-assembly process while the dimers of HES and SA had similar interactions, which could explain their structuring performance.

Preclinical Testing of a Novel Niclosamide Stearate Prodrug Therapeutic (NSPT) Shows Efficacy Against Osteosarcoma.

Therapeutic advances for osteosarcoma have stagnated over the past several decades, leading to an unmet clinical need for patients. The purpose of this study was to develop a novel therapy for osteosarcoma by reformulating and validating niclosamide, an established anthelminthic agent, as a niclosamide stearate prodrug therapeutic (NSPT). We sought to improve the low and inefficient clinical bioavailability of oral dosing, especially for the relatively hydrophobic classes of anticancer drugs. Nanoparticles were fabricated by rapid solvent shifting and verified using dynamic light scattering and UV-vis spectrophotometry. NSPT efficacy was then studied in vitro for cell viability, cell proliferation, and intracellular signaling by Western blot analysis; ex vivo pulmonary metastatic assay model; and in vivo pharmacokinetic and lung mouse metastatic model of osteosarcoma. NSPT formulation stabilizes niclosamide stearate against hydrolysis and delays enzymolysis; increases circulation in vivo with t 1/2 approximately 5 hours; reduces cell viability and cell proliferation in human and canine osteosarcoma cells in vitro at 0.2-2 µmol/L IC50; inhibits recognized growth pathways and induces apoptosis at 20 µmol/L; eliminates metastatic lesions in the ex vivo lung metastatic model; and when injected intravenously at 50 mg/kg weekly, it prevents metastatic spread in the lungs in a mouse model of osteosarcoma over 30 days. In conclusion, niclosamide was optimized for preclinical drug delivery as a unique prodrug nanoparticle injected intravenously at 50 mg/kg (1.9 mmol/L). This increased bioavailability of niclosamide in the blood stream prevented metastatic disease in the mouse. This chemotherapeutic strategy is now ready for canine trials, and if successful, will be targeted for human trials in patients with osteosarcoma.

Oleogels from sodium stearoyl lactylate-based lamellar crystals: Structural characterization and bread application.

Sodium stearoyl lactylate (SSL) was used as a gelling agent to structure oleogels at concentrations of 7%, 9%, 11%, and 13% (w/w) with sunflower oils in this study, respectively. The physical characteristics of oleogels, such as solid fat content (SFC), oil bonding capability (OBC) and firmness, were influenced by SSL crystals. Therefore, the microstructure and interaction of oleogels was further investigated by polarizing light microscopy (PLM), X-ray diffraction (XRD), rheology, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). It was found that the higher concentration of oleogelator resulted in a denser crystalline network, which provided stronger mechanical strength and enhanced the ability to retain the oil phase. Space-spanning networks were attributed to surface interactions among crystals of SSL, such as van der Waals interactions and electrostatic repulsion. Crystal network in the SSL oleogels imitated the typical functionality of crystalline network structures formed by triacylglycerol.

Lipase - catalyzed Modification of Rice Bran Oil Solid Fat Fraction.

This study used a rice bran oil solid fat fraction (RBOSF) to produce cocoa butter alternatives via interesterification reaction catalyzed by immobilized lipase (Lipozyme® RM IM) in hexane. Effects of reaction time (6, 12, and 18 h), temperature (55, 60, and 65°C), mole ratios of 3 substrates [RBOSF:palm olein:C18:0 donors (1:1:2, 1:2:3, and 1:2:6)] were determined. The substrate system was dissolved in 3 mL of hexane and 10% of lipase was added. Two sources of C18:0 donors, stearic acid (SAd) and ethyl stearate (ESd) were used. Pancreatic lipase - catalyzed sn-2 positional analysis was also performed on both substrates and structured lipids (interesterification products). Structured lipids (SL) were analyzed by gas - liquid chromatography (G40.35LC) for fatty acid composition. Major fatty acids of RBOSF were C18:1, oleic acid (OA, 41.15±0.01%), C18:2, linoleic acid (LA, 30.05±0.01%) and C16:0, palmitic acid (PA, 22.64±0.01%), respectively. A commercial raw cocoa butter (CB) contained C18:0, stearic acid (SA, 33.13±0.04%), OA (32.52±0.03%), and PA (28.90±0.01%), respectively. Fatty acids at sn-2 position of RBOSF were OA (46.52±0.63%) and LA (42.98±1.1%), while major fatty acid at sn-2 position of CB was OA (85.24±1.22%). The RBOSF had low SA (2.40±0.01%) compared to CB (33.13±0.04%). The content of OA (46.52±0.63%) at sn-2 position in RBOSF was half of that found in CB (85.24±1.22%). Optimal reaction was 1:2:6 mole ratio of the substrate (RBOSF:PO:SAd), at 65°C for 12 h. Fatty acid compositions of the SL were 31.72±0.99% SA, 30.91±0.53% LA, 23.18±0.32% OA, and 13.26±0.34% PA, respectively. Fatty acids at sn-2 position of the SL were 53.72±4.21% OA, 25.11±3.69% LA, 14.18±1.58% PA, and 6.99±0.02% SA, respectively. DSC curves showed the melting point of CB at 20.94°C, while those of the SL were 14.15 and 40.35°C, respectively. The melting completion temperature (Tmc) of CB was 25.5°C while that of SL was 43.9°C, respectively.

New Octadecanoid Enantiomers from the Whole Plants of Plantago depressa.

In this study, 19 octadecanoid derivatives-four pairs of enantiomers (1⁻8), two racemic/scalemic mixtures (9⁻10), and nine biosynthetically related analogues-were obtained from the ethanolic extract of a Chinese medicinal plant, Plantago depressa Willd. Their structures were elucidated on the basis of detailed spectroscopic analyses, with the absolute configurations of the new compounds assigned by time-dependent density functional theory (TD-DFT)-based electronic circular dichroism (ECD) calculations. Six of them (1, 3⁻6, and 9) were reported for the first time, while 2, 7, and 8 have been previously described as derivatives and are currently obtained as natural products. Our bioassays have established that selective compounds show in vitro anti-inflammatory activity by inhibiting lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells.

Oral administration of lipid oil-in-water emulsions performed with synthetic or protein-type emulsifiers differentially affects post-prandial triacylglycerolemia in rats.

In this study, we compared the impact of administration of size-calibrated lipid emulsions prepared with either synthetic or natural emulsifiers on the post-absorptive plasma triacylglycerol responses in rats. We did this using four types of size-calibrated (10 µm diameter) and metastable (3 days) emulsions with 20% of an oleic acid-rich sunflower oil and 1% of either synthetic emulsifiers (Tween 80 or sodium 2-stearoyl-lactylate) or two proteins (ß-lactoglobulin or sodium caseinate). An oral fat tolerance test was performed in fasted rats by oral administration of each of these formulations in continuous or emulsified forms. Kinetic parameters (AUC0-inf., AUC0-6h, Cmax, Tmax, and T1/2) for the description of the plasma triacylglycerol responses were calculated. AUC0-6h and AUC0-inf. calculated for the protein groups were significantly lower than those of the control and the synthetic groups. These lower values were associated with significant decreases in the Cmax, exacerbated by the emulsion form and with marked decreases in the Tmax as compared to the control group. T1/2 values were differentially affected by the lipid administration forms and by the nature of the emulsifiers. As compared with the control group, T1/2 was largely increased in the sodium stearoyl-2-lactylate group, but on the contrary, largely lowered in the casein group. We concluded that the use of proteins as natural emulsifiers in lipid emulsions decreased the magnitude of post-prandial triacylglycerolemia for the same amount of ingested lipids, when the emulsion size is controlled for. Proteins could be a promising alternative to the widespread use of synthetic emulsifiers in the food industry.

Nebulized coenzyme Q10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy.

Coenzyme Q10 (CoQ10) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ10 nanosuspensions designed to be administered to the lungs by nebulization. Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ10 formulations. Preparations were identified as nanosuspensions (particle size in the range 35-60nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ10 delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02µm). Stability tests showed that the most stable formulation, after 90days, was the one containing vitamin-E TPGS, followed by the CoQ10-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ10.

Surface active properties of lipid nanocapsules.

Lipid nanocapsules (LNCs) are biomimetic nanocarriers used for the encapsulation of a broad variety of active ingredients. Similar to surface active compounds, LNCs contain both hydrophilic and hydrophobic parts in their structure. Moreover, the components of LNCs, macrogol 15 hydroxystearate (MHS) and lecithin, are known for their surface active properties. Therefore, the aim of this paper was to investigate the capability of the LNCs to decrease surface tension using two techniques: drop tensiometry and the Wilhelmy plate method. LNCs with diameters ranging from 30 to 100 nm were successfully obtained using a phase inversion technique. The LNCs' properties, such as size and zeta potential, depend on the composition. LNCs exhibit a lower limiting surface tension compared to MHS (34.8-35.0 mN/m and 37.7-38.8 mN/m, respectively), as confirmed by both drop tensiometry and the Wilhelmy plate method. LNCs have exhibited a saturated interfacial concentration (SIC) that was 10-fold higher than the critical micellar concentration (CMC) of MHS or the SIC of binary and ternary mixtures of LNC ingredients. The SIC of the LNC formulations depended on the mass mixing ratio of the MHS/triglycerides but not on the presence of lecithin. The CMC/SIC values measured by the Wilhelmy plate method were higher than those obtained using drop tensiometry because of the longer duration of the tensiometry measurement. In conclusion, the surfactant-like properties of the LNCs offer new possibilities for medical and pharmaceutical applications.

Combined effect of shearing and cooling rate on the rheology of organogels developed by selected gelators.

In this study we investigated the combined effect of shearing and cooling rate in the rheology of organogels developed in high oleic safflower oil by (R)-12-hydroxystearic acid (HSA), its primary amide derivative [(R)-12-hydroxyoctadecanamide, HOA], and the N-octadecyl derivative of HOA [(R)-N-octadecyl-12-hydroxyoctadecanamide, OHOA]. The experimental set up to develop the organogels involved: 1). The use of quiescent (0s-1) or shearing (300, 600, and 1200s-1) conditions during cooling the gelator solutions (2%) just until achieving the gelator's melting temperature (TM) in the vegetable oil, to then continuing the cooling under static conditions until achieving 15°C) The use of cooling rate protocols involving a constant cooling rate of 1°C/min (CR1) or 10°C/min (CR10) in the shearing and static stages, or variable cooling rates in each stage (i.e., VR1-10 or VR10-1). The elasticity of the organogels (G') was measured while cooling under static conditions, once the systems achieved 15°C, and after 60min at this temperature. The rheological results obtained at 15°C showed a cooling rate and molecular weight-dependent effect of shearing on G'. We propose that the molecular relaxation time of gelator molecules, and its increase as molecular weight increases and as temperature decreases, plays an important role on the gelator's susceptibility to go through a shear induced crystallization process. Therefore, high molecular weight molecules like OHOA (551.97Da) would remain stretched by shearing longer times than HSA (300.49Da) and HOA (299.49Da). Thus, when shearing was applied while cooling at the higher cooling rate (i.e., CR10 and VR10-1), the stretched OHOA molecules would lead to the development of mesophase precursors that upon further cooling under quiescent conditions, crystallize developing a well-structured organogel. In contrast, stretched low molecular weight molecules (i.e., HSA and HOA) with shorter relaxation time would dissolve back to the isotropic state during cooling. Additionally, the rheological results of HSA and HOA organogels suggested that the shear induced crystallization process might be dependent on the gelator polarity also. These results show that the application of shear and the extent of its application as temperature decreases until achieving TM, have important implication on the self-assembly of gelator molecules, and therefore in the organization and rheology of the three-dimensional crystal network of the organogel.

Construction and in vitro/in vivo evaluation of 17-allylamino-17-demethoxygeldanamycin (17AAG)-loaded PEGylated nanostructured lipid carriers.

In this study, the PEGylated nanostructured lipid carriers (PEG-NLC) were constructed for the intravenous delivery of 17-allylamino-17-demethoxygeldanamycin (17AAG). 17AAG-PEG-NLC was successfully prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature using a mixture of glycerol monostearate and PEG2000-stearate as solid lipids, and medium-chain triglyceride as the liquid lipid. The results revealed that the morphology of the NLC was spheroidal. The particle size, zeta potential and entrapment efficiency for 17AAG-PEG-NLC were observed as 189.4 nm, -20.2 mV and 83.42%, respectively. X-ray diffraction analysis revealed that 17AAG existed as amorphous structures in the nanoparticles. In the in vitro release study, the 17AAG from 17AAG-PEG-NLC exhibited a biphasic release pattern with burst release initially and sustained release afterwards. In addition, 17AAG-PEG-NLC showed a significantly higher in vitro antitumor efficacy and longer retention time in vivo than 17AAG solution. These results indicated that 17AAG-PEG-NLC may offer a promising alternative to the current 17AAG formulations for the treatment of solid tumors.

Enzymatic interesterification of soybean oil and methyl stearate blends using lipase immobilized on magnetic Fe3O4/SBA-15 composites as a biocatalyst.

The magnetic Fe3O4/SBA-15 composites were prepared, and treated with 3-aminopropyltriethoxysilane as a carrier material for enzyme immobilization. The immobilization of Candida rugosa lipase onto the amino-functionalized Fe3O4/SBA-15 composite was investigated by using glutaraldehyde as a coupling reagent. The immobilized lipase was then employed as a biocatalyst for the interesterification of soybean oil and methyl stearate in a laboratory-scale operation at 45°C. Various techniques, such as Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (XRD), and vibrating sample magnetometry (VSM), were used for the characterization of the immobilized lipase composite. The immobilized lipase behaved superparamagnetic and showed excellent response at applied magnetic field. The obtained results showed that the immobilized lipase could efficiently catalyze the interesterification reaction. Moreover, the interesterification reaction parameters, such as reaction temperature, substrate ratio and reaction time were investigated regarding the stearoyl incorporation into the triacylglycerols. Further, the immobilized lipase proved to be easily separated from the reaction mixture by applying an external magnetic field and to be stable in the repeated use for four cycles.

Isotopologue profiling of triterpene formation under physiological conditions. Biosynthesis of lupeol-3-(3'-R-hydroxy)-stearate in Pentalinon andrieuxii.

The biosynthesis of lupeol-3-(3'R-hydroxy)-stearate (procrim b, 1) was investigated in the Mexican medicinal plant Pentalinon andrieuxii by (13)CO2 pulse-chase experiments. NMR analyses revealed positional enrichments of (13)C2-isotopologues in both the triterpenoid and the hydroxystearate moieties of 1. Five of the six isoprene units reflected a pattern with [1,2-(13)C2]- and [3,5-(13)C2]-isotopologues from the respective C5-precursors, IPP and DMAPP, whereas one isoprene unit in the ring E of 1 showed only the [3,5-(13)C2]-connectivity of the original C5-precursor, due to rearrangement of the dammarenyl cation intermediate during the cyclization process. The presence of (13)C2-isotopologues was indicative of [(13)C2]acetyl-CoA being the precursor units in the formation of the fatty acid moiety and of the triterpene via the mevalonate route. The observed labeling pattern was in agreement with a chair-chair-chair-boat conformation of the (S)-2,3-oxidosqualene precursor during the cyclization process, suggesting that the lupeol synthase from P. andrieuxii is of the same type as that from Olea europea and Taraxacum officinale, but different from that of Arabidopsis thaliana. The study shows that (13)CO2 pulse-chase experiments are powerful in elucidating, under in vivo conditions and in a single experiment, the biosynthesis of complex plant products including higher terpenes.

Thermal responsive micelles for dual tumor-targeting imaging and therapy.

Two kinds of thermally responsive polymers P(FAA-NIPA-co-AAm-co-ODA) and P(FPA-NIPA-co-AAm-co-ODA) containing folate, isopropyl acrylamide and octadecyl acrylate were fabricated through free radical random copolymerization for targeted drug delivery. Then the micelles formed in aqueous solution by self-assembly and were characterized in terms of particle size, lower critical solution temperature (LCST) and a variety of optical spectra. MTT assays demonstrated the low cytotoxicity of the control micelle and drug-loaded micelle on A549 cells and Bel 7402 cells. Then fluorescein and cypate were used as model drugs to optimize the constituents of micelles for drug entrapment efficiency and investigate the release kinetics of micelles in vitro. The FA and thermal co-mediated tumor-targeting efficiency of the two kinds of micelles were verified and compared in detail at cell level and animal level, respectively. These results indicated that the dual-targeting micelles are promising drug delivery systems for tumor-targeting therapy.

Interfacial behaviour of sodium stearoyllactylate (SSL) as an oil-in-water pickering emulsion stabiliser.

The ability of a food ingredient, sodium stearoyllactylate (SSL), to stabilise oil-in-water (O/W) emulsions against coalescence was investigated, and closely linked to its capacity to act as a Pickering stabiliser. Results showed that emulsion stability could be achieved with a relatively low SSL concentration (≥0.1 wt%), and cryogenic-scanning electron microscopy (cryo-SEM) visualisation of emulsion structure revealed the presence of colloidal SSL aggregates adsorbed at the oil-water interface. Surface properties of SSL could be modified by altering the size of these aggregates in water; a faster decrease in surface tension was observed when SSL dispersions were subjected to high pressure homogenisation (HPH). The rate of SSL adsorption at the sunflower oil-water interface also increased after HPH, and a higher interfacial tension (IFT) was observed with increasing SSL concentration. Differential scanning calorimetry (DSC) enabled a comparison of the thermal behaviour of SSL in aqueous dispersions with SSL-stabilised O/W emulsions. SSL melting enthalpy depended on emulsion interfacial area and the corresponding DSC data was used to determine the amount of SSL adsorbed at the oil-water interface. An idealised theoretical interfacial coverage calculation based on Pickering emulsion theory was in general agreement with the mass of SSL adsorbed as predicted by DSC.

Effects of chemical interesterification on the physicochemical, microstructural and thermal properties of palm stearin, palm kernel oil and soybean oil blends.

Blends of palm stearin (PS), palm kernel oil (PKO) and soybean oil (SBO) at certain proportions were formulated using a mixture design based on simplex-lattice (Design Expert 8.0.4 Stat-Ease Inc., Minneapolis, 2010). All the 10 oil blends were subjected to chemical interesterification (CIE) using sodium methoxide as the catalyst. The solid fat content (SFC), triacylglycerol (TAG) composition, thermal properties (DSC), polymorphism and microstructural properties were studied. Palm-based trans-free table margarine containing ternary mixture of PS/PKO/SBO [49/20/31 (w/w)], was optimally formulated through analysis of multiple isosolid diagrams and was found to have quite similar SMP and SFC profile as compared to the commercial table margarine. This study has shown chemical interesterification are effective in modifying the physicochemical properties of palm stearin, palm kernel oil, soybean oil and their mixtures.

MALDI-TOF MS imaging of controlled release implants.

MALDI-TOF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) imaging is used to characterize novel lipid implants allowing for controlled drug delivery. Importantly, this innovative technique provides crucial information on the inner structure of the implants before and after exposure to the release medium and does not require the addition of marker substances. Implants were prepared by extrusion at room temperature. Thus, in contrast to hot-melt extruded systems, the risks of drug inactivation and solid state transformations of the lipid matrix former are reduced. Hydrogenated/hardened soybean oil and glyceryl tristearate were studied as lipids and propranolol hydrochloride and theophylline as drugs, exhibiting significantly different solubility in water. The implants were also characterized by optical microscopy, differential scanning calorimetry, water uptake and lipid erosion studies, mathematical modeling as well as in vitro drug release measurements. Importantly, broad spectra of drug release patterns with release periods ranging from a few days up to several months could easily be provided when varying the initial drug content and type of lipid, irrespective of the type of drug. The diameter of the implants can be as small as 1mm, facilitating injection. MALDI-TOF MS imaging revealed homogeneous macroscopic drug distributions within the systems, but steep drug concentration gradients in radial and axial direction at the lower micrometer level, indicating drug- and lipid-rich domains. As the implants do not significantly swell, local irritation upon administration due to mechanical stress can be expected to be limited. Good agreement between experimentally measured and theoretically calculated drug release kinetics revealed that diffusional mass transport plays a major role for the control of drug release from this type of advanced drug delivery systems.

Poly(ethylene glycol) hydroxystearate-based nanosized emulsions: effect of surfactant concentration on their formation and ability to solubilize quercetin.

Quercetin is a natural compound that has shown several biological activities. However, it displays poor water solubility and, therefore, low bioavailability. In this study, oil-in-water nanosized emulsions were obtained by the hot solvent diffusion method, using castor oil as oily phase and poly(ethylene glycol) (660)-12-hydroxystearate (PEG 660-stearate) and lecithin as surfactants. The effect of the PEG 660-stearate concentration on the droplet size of the nanosized emulsions and on the ability of these systems to load quercetin was investigated. Dynamic light scattering (DLS), transmission electron microscopy (TEM), cryo-TEM, and small-angle X-ray scattering (SAXS) were used to characterize the systems. We have demonstrated that a critical concentration of PEG 660-stearate (2.5 wt%) was needed to obtain colloidal dispersions displaying microemulsion characteristics. This colloidal dispersion, that was not optically birefringent, was constituted by a monodisperse population of 20 nm-large droplets, and exhibited excellent stability. Besides, this system was able to solubilize five times more quercetin than nanoemulsions prepared using 0.25 wt% PEG 660-stearate. SAXS results suggest that the spherical droplets have a core-shell structure. With regard to the hot solvent diffusion method, both diffusion of the solvent towards the aqueous phase and increase of the temperature above the phase inversion temperature (PIT) of PEG 660-stearate appeared to be required for obtaining clear and isotropic colloidal dispersions.