Gabriela Elena Badea

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.

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.

Integrative approach in prevention and therapy of basal cellular carcinoma by association of three actives loaded into lipid nanocarriers

Basal cell carcinoma (BCC) is one of the commonest malignancies occurred on sun-exposed skin, mainly by UV-B radiation, of lighter-skinned individuals. The aim of the present study was to develop advanced drug delivery formulations used in BCC therapy that overcomes chemotherapy-induced side-effects of skin photosensitivity by an integrative approach of nanoencapsulation in conjunction with combination therapy that uses chemotherapeutic, chemoprotective and sunscreen agents. The combination of anticancer drug together with sunscreen agent is very useful in therapy, especially for individuals who are more exposed to the sun without using a sunscreen. Nanostructured lipid carriers (NLCs) employed as drug delivery systems were co-loaded with 5-fluorouracil (5-FU), a hydrophilic chemotherapeutic drug, and ethylhexyl salicylate (EHS), a lipophilic UV-B sunscreen agent. The NLCs were developed using bioactive squalene (50.8% w/w) from amaranth seed oil as chemoprotective agent. By varying the concentrations of 5-FU and EHS, the co-loaded NLCs presented particle sizes of about 100nm, acceptable physical stability with values smaller than -25mV and appropriate entrapment efficiency that reaches values over 65% for both types of drugs. The UV-B blocking ability of EHS loaded into NLCs were influenced by the concentration of 5-FU. The amaranth oil offered a capacity of 70% in scavenging the free radicals. In vitro drug release showed that NLCs presented sustained release of 5-FU that followed the Ficks law of diffusion.

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.