Polymeric nanocapsules prevent oxidation of core-loaded molecules: evidence based on the effects of docosahexaenoic acid and neuroprostane on breast cancer cells proliferation

Abstract

BackgroundNanocapsules, as a delivery system, are able to target drugs and other biologically sensitive molecules to specific cells or organs. This system has been intensively investigated as a way to protect bioactives drugs from inactivation upon interaction with the body and to ensure the release to the target. However, the mechanism of improved activity of the nanoencapsulated molecules is far from being understood at the cellular and subcellular levels. Epidemiological studies suggest that dietary polyunsaturated fatty acids (PUFA) can reduce the morbidity and mortality from breast cancer. This influence could be modulated by the oxidative status of the diet and it has been suggested that the anti-proliferative properties of docosahexaenoic acid (DHA) are enhanced by pro-oxidant agents.MethodsThe effect of encapsulation of PUFA on breast cancer cell proliferation in different oxidative medium was evaluated in vitro. We compared the proliferation of the human breast cancer cell line MDA-MB-231 and of the non-cancer human mammary epithelial cell line MCF-10A in different experimental conditions.ResultsDHA possessed anti-proliferative properties that were prevented by alpha-tocopherol (an antioxidant) and enhanced by the pro-oxidant hydrogen peroxide that confirms that DHA has to be oxidized to exert its anti-proliferative properties. We also evaluated the anti-proliferative effects of the 4(RS)-4-F4t-neuroprostane, a bioactive, non-enzymatic oxygenated metabolite of DHA known to play a major role in the prevention of cardiovascular diseases. DHA-loaded nanocapsules was less potent than non-encapsulated DHA while co-encapsulation of DHA with H2O2 maintained the inhibition of proliferation. The nanocapsules slightly improves the anti-proliferative effect in the case of 4(RS)-4-F4t-neuroprostane that is more hydrophilic than DHA.ConclusionOverall, our findings suggest that the sensitivity of tumor cell lines to DHA involves oxidized metabolites. They also indicate that neuroprostane is a metabolite participating in the growth reducing effect of DHA, but it is not the sole. These results also suggest that NC seek to enhance the stability against degradation, enhance cellular availability, and control the release of bioactive fatty acids following their lipophilicities.

Impact of dose and surface features on plasmatic and liver concentrations of biodegradable polymeric nanocapsules

“…For spherical particles R g /R h of 0.775 is characteristic of spheres with uniform density, such as polystyrene latexes (Brewer and Striegel, 2009), values close to 1.0 are obtained with vesicles or hollow spheres (Stauch et al, 2002;Vezočnik et al, 2015), values above 1 are obtained with elongated or porous structures and values as low as 0.3 are characteristic of microgels (Kunz et al, 1983). These values are in agreement with literature values for similar types of NC (Roy et al, 2015) and liposomes (Vezočnik et al, 2015). The higher R g /R h for PLA-PEG NC may be attributed to the PEG corona creating a dense hydration layer around the oil-polymer vesicle…”

Physiological role of reactive oxygen species as promoters of natural defenses

“…Recently, Roy et al , showed that the oxidation of ω‐3 PUFAs by ROS releases 4( RS )‐4‐F 4t ‐NeuroP from docosahexaenoic acid, which is necessary to prevent isoproterenol‐induced arrhythmias in mice with myocardial infarction (173), prevent early arrhythmias in rats after an ischemia/reperfusion period (174), or prevent breast cancer proliferation (175). As previously observed in different oxidative conditions (176), the researchers proposed that in oxidative stress conditions, such as ischemic events, 4( RS )‐4‐F 4t ‐NeuroP is responsible for the antiarrhythmic properties of ω‐3 PUFAs by countering the cellular stress by ROS.…”

<p>Nanomedicine-based formulations containing &omega;-3 polyunsaturated fatty acids: potential application in cardiovascular and neoplastic diseases</p>

“…Moreover, when it is encapsulated at lower concentrations, it seems to even promote breast cancer cell growth. 50 On the other hand, Alaarg et al 58 enclosed DHA into liposomes by using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, and distearoyl phosphatidylethanolamine (PE); and polyethylene glycol (PEG) and these liposomes were used for the delivery of DHA to murine breast cancer cells in vitro (Table 3; Figure 2B). PEGylated liposomes were chosen for their acknowledged ability to stay in the circulation for a longer period (about 1 day half-life) compared to non-PEGylated particles that are cleared from the circulation in #1 hour.…”