Synergism of plant extract and vegetable oils-based lipid nanocarriers: Emerging trends in development of advanced cosmetic prototype products.

Phytochemicals are priceless sources of bioactive compounds with multiple health benefices. The main objective of the current investigation was to develop nanostructured herbal formulations conditioned as appropriate hydrogel (HG) conferring an enhanced transdermal absorption of bioactive compounds from selective extracts and vegetable oils. The direct impact of research is represented by the identification of prototype products which manifest an improved therapeutic response, by means of cumulative antioxidant, anti-inflammatory and anti-acne actions, without causing any side health effects. The combinatorial effect of Carrot Extract (CE) and Marigold Extract (ME) - Nanostructured Lipid Carriers (NLC) based on rosehip oil or black cumin oils was accompanied by a high biocompatibility and a significant ability to capture both short- and long-life free radicals. HG-NLC-ME-CE has been shown to be an efficient carrier with a differentiated potential for in vitro release of the two active principles, e.g. it delayed the release of carotenoids while the hydrophilic active (azelaic acid, AA) was faster released. The HG-NLC efficacy in skin inflammation treatment (demonstrated by in vitro and in vivo tests) revealed a reduced expression of inflammatory cytokines (IL-1ß and TNF-α), more pronounced in the case of TNF-α. Moreover, a superior in vivo anti-inflammatory effect of HG-based NLC-CE/ME-AA as compared to that obtained for a commercial product was detected, i.e. after 3 h of HG-NLC treatment, a significant reduction of rat paw edema was quantified. In pre-clinical studies, the quantification of the hydration and elasticity effects in the viable epidermis provided the evidence of the high potential of developed prototypes, suitable for implementation in the market area. The degree of skin hydration and skin elasticity were remarkable enhanced after topical application of developed prototypes, a hydration effect up to 74% being determined and a skin elasticity reaching 90%. The knowledge acquired from this investigation could be utilized by the cosmetic industry to design novel topical products with improved quality and health benefices, endowed with antioxidant, anti-inflammatory and anti-acne actions and with desired hydration and elasticity profiles, in order to achieve better therapeutic efficacy and no drug toxicity.

Improved anti-obesity effect of herbal active and endogenous lipids co-loaded lipid nanocarriers: Preparation, in vitro and in vivo evaluation.

The association of numerous advantages of natural active compounds (from vegetal and herbs) and endogenous lipid in the same delivery system is a straightforward approach for the development of safe and better tolerated anti-obesity therapy. In the present study we envisage a novel concept for obesity therapy, devoted to the development of innovative lipid nanostructured formulas with improved gastric tolerability and enhanced specificity in adipose cells targeting. For this purpose, an anti-obesity herbal active from red pepper extract - Capsaicin (Cap) and an endogenous lipid regulator of appetite - oleoylethanolamide (OEA) or a structural analogue of OEA - Phenylalaninol oleamide (PAO), are simultaneously integrated within the same delivery system - nanostructured lipid carriers (NLC) prepared with linseed oil that has anti-inflammatory and hypotriglyceridemic properties. The NLC-OEA/PAO-Cap presented mean diameters under 200 nm, size that allow an efficient uptake of actives by enterocytes and lead to an extended biological action of all actives - Cap, OEA/PAO and linolenic acid. NLC revealed a polidispersity index ranging from 0.16 to 0.22, which represents a narrow dispersion around mean size and suggests an adequate unimodal behavior. The two types of NLC co-loaded with Cap and OEA/PAO were both negatively charged, with zeta potentials of -42.8 mV and -58.5 mV that offered a guarantee for an excellent stability of NLC in time. Despite to the competition between the accommodations of both actives into the lipid core of nanocarriers, the entrapment efficiency exceeds 92% for OEA/PAO and is ranged between 71 and 82% for Cap. In the presence of NLC-OEA/PAO-Cap, ABTS+⁎ inhibition proceeded in a Capsaicin concentration dependent manner and was dependent on the type of NLC formulation. A remarkable radical-scavenging activity against ABTS+⁎ was determined for Cap and OEA based-NLC. The in vitro release demonstrated that NLC played an important role on the delay of Cap dissolution; the NLC have ensured a slow release of Cap, eg only 21% Cap was released after 24 h of in vitro experiments. The in vivo pharmacological evaluation has revealed that the NLC-OEA/PAO-Cap treatment resulted in a body weight decrease and improves the lipid and glucose profile, as compared to the obese mice batch. Obesity mice treated with NLC-OEA exhibited a weight loss of ~15% and ~10% weight loss for NLC-POA, after 10-days treatment. Administration of NLC-OEA/PAO-Cap to the Albino Swiss mice led to significant decrease of glucose level (e.g. 117.4 mg/dL for NLC-OEA-Cap treated mice versus 213.9 mg/dL for obese mice batch) and exhibited a desired decrease effect of triglyceride (e.g. 71.1 mg/dL for NLC-OEA-Cap versus 129.5, for obese batch). Moreover, the cholesterol values have been lowered to almost half from the value determined for the control batches. Overall, study highlights that using appropriate lipid mediators in association with an herbal anti-obesity active, both formulated into lipid nanocarriers, could enhance the therapeutic response in the obesity treatment.

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.

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.

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 ß-sitosterol/ß-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 ß-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.

Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect.

The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions.