Raluca Stan

Novel bio-active lipid nanocarriers for the stabilization and sustained release of sitosterol.

In this work, new stable and efficiently bio-active lipid nanocarriers (NLCs) with antioxidant properties have been developed for the transport of active ingredients in food. The novel NLCs loaded with β-sitosterol/β-sitosterol and green tea extract (GTE) and prepared by a combination of natural oils (grape seed oil, fish oil and squalene) and biological lipids with food grade surfactants, were physico-chemically examined by DLS, TEM, electrokinetic potential, DSC and HPLC and found to have main diameters less than 200 nm, a spherical morphology, excellent physical stability, an imperfect crystalline lattice and high entrapment efficiency. The novel loaded-NLCs have demonstrated the potential to develop a high blocking action of chain reactions, trapping up to 92% of the free-oxygen radicals, as compared to the native β-sitosterol (AA%=36.5). Another advantage of this study is associated with the quality of bio-active NLCs based on grape seed oil and squalene to manifest a better sitosterol-sustained release behaviour as compared to their related nanoemulsions. By coupling both in vitro results, i.e. the enhanced antioxidant activity and superior release properties, this study emphasizes the sustainability of novel bio-active nanocarriers to gain specific bio-food features for development of functional foods with a high applicability spectrum.

Influence of vegetable oil on the synthesis of bioactive nanocarriers with broad spectrum photoprotection

Due to their unique features, most nanostructured lipid carriers (NLCs) in association with vegetable oils that exhibit UV filtering properties and bioactivity could be used in many cosmetic formulations. Therefore, in this work, a new application of pomegranate seed oil (PSO) in the cosmetic sector was developed, based on the synthesis of bioactive lipid nanocarriers loaded with various UV filters by the hot high pressure homogenization technique. To get broad spectrum photoprotection, different UVA and UVB filters have been used (Avobenzone — AVO, Octocrylen-OCT, Bemotrizinol — BEMT). The influence of the solid lipids combined with PSO on the particle size, physical stability and entrapment efficiency was investigated using 8 nanocarrier systems. An improved physical stability and an appropriate size were obtained for NLCs prepared with Emulgade, carnauba wax and PSO (e.g. −30.9÷-36.9 mV and 160÷185 nm). NLCs showed an entrapment efficiency above 90% and assured slow release rates of UV filters, especially for BEMT (5%). The developed nanocarriers have been formulated into safe and effective sunscreens containing low amounts of synthetic UV filters coupled with a high percent of natural ingredients. The highest SPF of 34.3 was obtained for a cream comprising of 11% PSO and 3.7% BEMT

Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5mg·mL(-1) has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5mg·mL(-1) lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications.

Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage.

The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to -45mV) and displayed average sizes of 70nm to 140nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract-bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α.

Hybrid networks based on epoxidized camelina oil

Abstract Lately, renewable resources received great attention in the macromolecular compounds area, regarding the design of the monomers and polymers with different applications. In this study the capacity of several modified vegetable oil-based monomers to build competitive hybrid networks was investigate, taking into account thermal and mechanical behavior of the designed materials. In order to synthesize such competitive nanocomposites, the selected renewable raw material, camelina oil, was employed due to the non-toxicity and biodegradability behavior. General properties of epoxidized camelina oil-based materials were improved by loading of different types of organic-inorganic hybrid compounds – polyhedral oligomeric silsesquioxane (POSS) bearing one (POSS1Ep) or eight (POSS8Ep) epoxy rings on the cages. In order to identify the chemical changes occurring after the thermal curing reactions, FT-IR spectrometry was employed. The new synthesized nanocomposites based on epoxidized camelina oil (ECO) were characterized by dynamic mechanical analyze and thermogravimetric analyze. The morphology of the ECO-based materials was investigate by scanning electron microscopy and supplementary information regarding the presence of the POSS compounds were establish by energy dispersive X-ray analysis and X-ray photoelectron spectroscopy. The smooth materials without any separation phase indicates a well dispersion of the Si–O–Si cages within the organic matrix and the incorporation of this hybrid compounds into the ECO network demonstrates to be a well strategy to improve the thermal and mechanical properties, simultaneously.

Ivy leaves extract based – lipid nanocarriers and their bioefficacy on antioxidant and antitumor activities

In this study, two issues commonly associated with phytochemical based nanotechnology were addressed: (1) the use of active compounds from medicinal herbs as functional ingredients entrapped into lipid-based nanocarriers; (2) the safety and efficacy of phytochemical-based nanocarriers with promising antioxidant and antitumor benefits. In this context, nanostructured lipid carriers (NLC) based on raspberry seed oil (Rso), pomegranate seed oil (Pso) and rice bran oil (Rbo) were synthesized and proven to be highly effective for the entrapment of hydrophilic ivy leaves extract (Ile). The size, morphology, zeta potential, entrapment efficiency and crystallinity of the Ile-loaded NLC were characterized. The effectiveness of Ile loaded-NLC has been proved by identifying a high capacity to scavenge free oxygen radicals (i.e. between 94 and 98%). 200 μg mL−1 Ile-NLC based on Rbo showed no significant effects on cellular viability in the fibroblast L929 cell line, while the tumor B16 cell line was markedly affected. MTS, RTCA assays and apoptosis examination revealed that these nanocarriers induce cytotoxicity and apoptosis in the murine melanoma B16 cell line. This study reports the first evidence of the association of hydrophilic and lipophilic phytochemicals in the same lipid nanocarriers, which appears to be a promising antioxidant and antitumor approach deserving further investigation.

Naringenin improves the sunscreen performance of vegetable nanocarriers

The aim of this study was to evaluate the potential role of naringenin (NAR) in developing polyphenol-rich sunscreens by encapsulation into nanostructured lipid carriers (NLCs) based on vegetable oils. The functionality of NLCs loaded with NAR (NAR–NLC), NAR together with an UVA filter (NAR–UVA–NLC), and with an UVA filter (UVA–NLC) was evaluated by studying their photostability, UV protection factors, antioxidant activity and cytotoxic effect on L929 mouse fibroblasts. The photostability study revealed that NLCs loaded with NAR and/or the UVA filter were photostable under UV exposure. NAR–UVA–NLCs formulated into hydrogels exhibited the best photoprotection with an SPF of 8.4 and a UVAPF of 13.8, as compared with the same formulation without NAR which showed an SPF of 6 and a UVAPF of 10.5. The photoprotective values obtained for NAR–UVA–NLCs underline an efficient sunscreen performance, 87.5% of UVB radiation and 81.1% of UVA radiation being filtered. The antioxidant activity against short- and long-life radicals was also improved by co-loading NAR and a UVA filter into lipid nanocarriers. At low concentrations (25 and 50 μg mL−1) the nanocarriers showed no cytotoxicity and the presence of NAR inside the nanocarriers increased the cell viability. The in vitro drug release studies showed that the NLC system provides an increased release and permeation of NAR. All results indicated that NAR has the potential to be used in developing safer and efficient polyphenol-rich sunscreens, by improving the anti-UV and antioxidant performance of the vegetable nanocarriers.

Novel PEG-Modified Hybrid PLGA-Vegetable Oils Nanostructured Carriers for Improving Performances of Indomethacin Delivery

The purpose of this work was to more exhaustively study the influence of nanocarrier matrix composition and also the polyethylene glycol (PEG)-modified surface on the performances of formulations as lipophilic drug delivery systems. Poly (d,l-lactide-co-glycolide), two vegetable oils (Nigella sativa oil and Echium oil) and indomethacin were employed to prepare novel PEG-coated nanocarriers through emulsion solvent evaporation method. The surface modification was achieved by physical PEG adsorption (in the post-production step). Transmission electron microscopy (TEM) nanographs highlighted the core-shell structure of hybrid formulations while scanning electron microscopy (SEM) images showed no obvious morphological changes after PEG adsorption. Drug loading (DL) and entrapment efficiency (EE) varied from 4.6% to 16.4% and 28.7% to 61.4%, solely depending on the type of polymeric matrix. The oil dispersion within hybrid matrix determined a more amorphous structure, as was emphasized by differential scanning calorimetry (DSC) investigations. The release studies highlighted the oil effect upon the ability of nanocarrier to discharge in a more sustained manner the encapsulated drug. Among the kinetic models employed, the Weibull and Korsmeyer-Peppas models showed the better fit (R2 = 0.999 and 0.981) with n < 0.43 indicating a Fickian type release pattern. According to cytotoxic assessment the PEG presence on the surface increased the cellular viability with ~1.5 times as compared to uncoated formulations.

CONDENSATION REACTIONS OF PLANAR CHIRAL TRICARBONYL- CHROMIUM-COMPLEXED BENZYLIC ALCOHOLS AND ACETATES WITH REACTIVE ARENES

The condensation reaction of planar chiral 2- and 2,5-substituted tricarbonyl-chromium complexed benzylic alcohols and acetates with reactive arenes (durene, anisole, 1,3-dimethoxybenzene, diphenyl ether) is reported. The reactions were performed in both racemic and enantiomeric versions, optically pure R-(+)- and S-(-)-[2-methoxybenzyl alcohol]-tricarbonyl-chromium being prepared by LiAlH4 reduction of diastereomeric, t.l.c. separated, (-)-menthyl esters of [2-methoxybenzoic acis]-tricarbonyl-chromium. The condensation of the difunctional complex [1,4-diacetoxymethylene-2,5-dimethoxybenzene]-tricarbonyl-chromium with an excess of anisole proved the same reactivity at both reactive benzylic sites thus serving as a model for possible polycondensation process. Corresponding optically pure difunctional starting complexes were obtained by t.l.c. separation of diasteromeric diesters with R-(-)-lactic or S-(-)-mandelic acids.