In Vivo Gastroprotective Effect of Nanoparticles: Influence of Chemical Composition and Volume Fraction

Abstract

In nanomedicine, different nanomaterials and nanoparticles have been proposed as therapeutic agents or adjuvants, as well as diagnosis devices. Considering that the principal cause of the ulcerations is the imbalance among the gastric juice secretion and the protection provided by the mucosal barrier and the neutralization of the gastric acid, as well as that nanoparticles are able to accumulate in the gastro-intestinal tissues, we proposed a 2(2) factorial design to evaluate the influence of the chemical composition and the volume fraction of the dispersed phase on the gastric protective effect against ulceration induced by ethanol. Cocoa-theospheres (CT) and lipid-core nanocapsules (LNC) (two different kinds of surfaces: lipid and polymeric, respectively) prepared at two different concentrations of soft materials: 4% and 12% (w/v) were produced by high pressure homogenization and solvent displacement methods, respectively. Laser diffraction showed volume-weighted mean diameters ranging from 133 to 207 nm, number median diameters lower than 100 nm and specific surfaces between 41.2 and 51.2 m(2) g(-1). The formulations had pH ranging from 4.7 to 6.3; and zeta potential close to -9 mV due to their coating with polysorbate 80. The ulcer indexes were 0.40 (LNC(4)) and 0.48 (CT(4)) for the lower total administered areas (3.3 and 4.1 m(2)g(-1), respectively), and 0.09 (LNC(12) and CT(12)) for the higher administered areas (10.0 and 12.0 m(2) g(-1), respectively). LNC(4), LNC(12) and CT(12) showed lower levels in the lipid peroxidation assay when compared either to the negative control (saline) or to CT(4). LNC(12) and CT(12) showed similar TBARS levels, as well as CT(4) was similar to the negative control. SEM analysis of the stomach mucosa showed coatings more homogenous and cohesive when LNC formulations were administered compared to the correspondent CT formulations. The higher total area of administered nanoparticles showed film formation. Moreover, LNC(12) provided a more thick and cohesive film, completely covering the mucosal surface. In conclusion, both kinds of formulations are able to prevent ulceration induced by ethanol in rats. The 2(2) factorial design showed that the chemical composition had a strong influence when the lower areas of nanoparticles are administered, while when the higher areas are used this is the more influencing parameter on the gastroprotection.

Redispersible spray-dried lipid-core nanocapsules intended for oral delivery: the influence of the particle number on redispersibility

“…Some of the main advantages of drug-loaded LNC certainly point to their potential to increase drug bioavailability (Dimer et al 2014, Frozza et al 2013 and to improve antitumor activity (Figueiro et al 2013). In addition, LNC have gastroprotective effect (Bueno et al 2013) and the ability to modulate drug release through different skin layers (Fontana et al 2011).…”

Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models

“…[61][62][63] It is beyond question that involvement of reactive oxygen species (ROS) and RNS affects melanoma induction and development, but the complexity of actions has generated conflicting data. [64][65][66] Therefore, we will make efforts to characterize the mechanisms of LNC on ROS and RNS systems and to establish the real role of ROS/RNS balance and its involvement in the toxicity of LNC on melanoma cells.…”