Nanoparticles are submicrometric systems smaller than nm

Nanoparticles are submicrometric systems smaller than 1000 nm which high surface area and composite materials may allow their greater interaction with biological membranes and control of the drug release. These features are directly associated with the efficacy of treatment and the presence of adverse effects during conventional pharmacological therapy [25]. In order to improve cutaneous permeation and reduce Imq adverse effects, the present work aimed to encapsulate Imq into polymeric nanoparticles for topical use and evaluate antiangiogenic effect and chemopreventive activity of this system compared to the market formulation.
Materials and methods
Results
Discussion All nanocarriers presented values of polydispersity index (PDI) smaller than 0.2, indicating their homogeneous and unimodal distribution [29]. This data can be supported by NPPlacebo and NPImq photomicrographs that allowed to verify spherical particles around 200–300 nm, corroborating with DLS results. Both nanoparticles, placebo and Imq-loaded, showed negative zeta potential which would be expected due to the presence of carboxyl groups exposed at polymer chains of Eudragit® L100 [30]. The total value of zeta potential for the two formulations was also greater than 25 which is an indicative of good stability to aqueous dispersions [31]. Imq in vitro release from nanoparticles did not differ from the Imq in solution in the first 10 min of the study which may have occurred due to non-encapsulated drug fraction in dispersant medium or to the presence of adsorbed drug on particles surface which would consequently be released quickly [32,33]. On the other hand, from the 15 min time until the end of the assay, Imq release was significantly slower. Imq release from NPImq was also slower than marketed product from the 60 min time until the end of the study, indicating that such formulation showed greater control in release of active compound. Polymeric nanospheres loading paclitaxel and endostatin showed greater antiproliferative effect on human umbilical vascular endothelial 49 9 (HUVEC) compared to the same effect of these drugs in their free form. This result was associated to reduction of oxidation reactions and enzymatic degradation promoted by drug encapsulated in nanocarriers and its sustained release [34]. Magnolol-containing nanoparticles, isolated from Magnolia officinalis, and presenting antioxidant and antiproliferative properties, have demonstrated better uptake efficiency in vascular smooth muscle cells (VSMC) compared to free drug. These data were attributed to controlled release of the active substance through the nanoparticle shell that worked as a barrier to release process, which did not occur with free drug, rapidly depleted [35]. Considering the antitumoral effect, in our study, the number of papillomas and size distribution of NPImq treated group was significantly reduced when compared to other groups (Section 3.4). This effect could possibly be due to a combination of enhanced permeability and retention (EPR) effect [36,37,38], superior antiangiogenic activity of NPImq (Section 3.2), greater retention of Imq in deep layers of the skin promoted by nanoparticles (Section 3.3) and Imq slower release from nanoparticles compared to market formulation. Once tumors reach around 2 mm, new leaky vessels are developed to guarantee tumor nutrients and oxygen supply. It allows nanoparticles to reach tumor vasculature through endothelial gaps (100 nm to 2 μm) [38] and release the drug at the target site. Since colloidal systems presented more prolonged release of the drug (Section 3.1), nanocarriers could also form a reservoir system in addition to reducing drug degradation, leading to a bioavailability increasing which can be confirmed by Imq quantified in deeper layers of the skin (Section 3.3). This effect may represent an advantage in Imq therapy since its main mechanism of action occurs through the activation of antigen presenting cells, such as dendritic cells, present in the dermis [39]. Probable penetration pathways of nanoparticles in deep skin layers occurs through the hair follicles which allow the accumulation of these systems in the follicular openings [40], creating a reservoir system and releasing the drug slowly [41].