Glioblastoma is the most devastating primary brain tumor. Effective therapies are not available, mainly due to high tumor heterogeneity, chemoresistance, and the difficulties imposed by blood-brain barrier. CD73, an enzyme responsible for adenosine (ADO) production, is overexpressed in cancer cells and emerges as a target for glioblastoma treatment. Indeed, ADO causes a variety of tumor-promoting actions, particularly by inducing tumor immune escape, whereas CD73 inhibition impairs tumor progression. Here, a cationic nanoemulsion to deliver CD73siRNA (NE-siRNA CD73R) via nasal route aiming glioblastoma treatment was developed. NE-siRNA CD73R was uptaken by glioma cells in culture, resulting in a parallel 60-80% decrease in AMPase activity and 30-50% in cell viability. Upon nasal delivery, NE-siRNA CD73R was detected in rat brain and serum. Notably, treatment with CD73siRNA complexes of glioma-bearing Wistar rats reduced tumor growth by 60%. Additionally, NE-siRNA CD73R treatment decreased 95% ADO levels in liquor and tumor CD73 expression, confirming in vivo CD73 silencing. Finally, no toxicity was observed in either primary astrocytes or rats with this cationic nanoemulsion. These results suggest that nasal administration of cationic NE as CD73 siRNA delivery system represents a novel potential treatment for glioblastoma.

Vegetable oils present important pharmacological properties, which gained ground in the pharmaceutical field. Its encapsulation in nanoemulsions is considered a promising strategy to facilitate the applicability of these natural compounds and to potentiate the actions. These formulations offer several advantages for topical and systemic delivery of cosmetic and pharmaceutical agents including controlled droplet size, protection of the vegetable oil to photo, thermal and volatilization instability and ability to dissolve and stabilize lipophilic drugs. For these reasons, the aim of this review is to report on some characteristics, preparation methods, applications and especially analyze recent research available in the literature concerning the use of vegetable oils with therapeutic characteristics as lipid core in nanoemulsions, specially from Brazilian flora, such as babassu (Orbignya oleifera), aroeira (Schinus molle L.), andiroba (Carapa guaianiensis), casca-de-anta (Drimys brasiliensis Miers), sucupira (Pterodon emarginatus Vogel) and carqueja doce (Stenachaenium megapotamicum) oils.Uniterms: Plant oils/nanoemulsions/preparation. Plant oils/biological applications. INTRODUCTIONThe use of submicrometric colloidal nanocarriers such as nanoparticles (NP) lipid and polymeric, nanoemulsions (NE), microemulsions (ME), liposomes, and polymeric micelles is considered a promising system in the pharmaceutical field, because they have numerous advantages over traditional formulations such as: sustained release of the active element; solubilization of lipophilic molecules; use for different routes of administration; protection from chemical and enzymatic degradation of labile molecules; reduction of vegetable oils (VO) volatilization, side effects and dose (Mäder, Mehnert, 2005;Mehnert, Mäder, 2001;Gref, Couvreour, 2006;Couvreur, Vauthier, 2006; Panyam, Labhasetwar, 2003;Soppimath et al., 2001;Ai et al., 2011; Contri et al., 2012;Contri et al., 2014;Dimer et al., 2014;Severino et al., 2015;Frank et al., 2015;Asbahani et al., 2015). However, all systems differ thermodynamic stability, structure, chemical composition, efficiency encapsulation and types of application (Mäder, Mehnert, 2005;Ai et al., 2011).The development of suitable nanocarriers for pharmaceutical or cosmetic application requires the adequate selection of their adjuvants such as polymers for nanocapsules (NC), surfactants, and oils (Schaffazick et al., 2003;Alvarez-Román et al., 2001;Bouchemal et al., 2004;Friedrich et al., 2008). Recently, special attention has been given to the type of oily phase used as the core in the preparation of NE. VO has been preferred not only due to the concept that it is safe and biocompatible, but mainly because of the diversity of benefits, and the complex composition of fatty acids can exercise under the skin, protecting it against dehydration, solar radiation, inflammation, insect attack, microorganisms, and viruses (Tadros, Kessell, 2004;Bloise, 2003;Oyedeji, Okeke, 2010;Bakkali et. al., 2008;Harris, 2002; Contri et al, ...

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Kaempferol (KPF), an important flavonoid, has been reported to exert antioxidant, anti-inflammatory, and anticancer activity. However, this compound has low water solubility and hence poor oral bioavailability. This work aims to prepare a solid dispersion (SD) of KPF using Poloxamer 407 in order to improve the water solubility, dissolution rate, and pharmacokinetic properties KPF. After optimization, SDs were prepared at a 1:5 weight ratio of KPF:carrier using the solvent method (SD SM ) and melting method (SD MM ). Formulations were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) analysis, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The solubility in water of carried-KPF was about 4000-fold greater than that of free KPF. Compared with free KPF or the physical mixture, solid dispersions significantly increased the extent of drug release (approximately 100% within 120 min) and the dissolution rate. Furthermore, after oral administration of SD MM in rats, the area under the curve (AUC) and the peak plasma concentration (C max ) of KPF from SD MM were twofold greater than those of free KPF (p < 0.05). In conclusion, SD with Poloxamer 407 is a feasible pharmacotechnical strategy to ameliorate the dissolution and bioavailability of KPF.

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 2 factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice. The type of polymer influenced all of the responses studied. Quinine-loaded Eudragit RS100 (F13) and PCL nanocapsules (F9), both with polysorbate 80 coating, showed nanometric particle size, positive zeta potential, neutral pH, high drug content, and quinine photoprotection ability; thus, these nanocapsules were selected for in vivo tests. Both formulations showed lower levels of parasitemia from the beginning of the experiment (5.78 ± 3.60 and 4.76 ± 3.46% for F9 and F13, respectively) and highest survival mean time (15.3 ± 2.0 and 14.9 ± 5.6 days for F9 and F13, respectively). F9 and F13 showed significant survival curve compared to saline, thus demonstrating that nanoencapsulation improved bioefficacy of QN and co-encapsulated curcuminoids, regardless of the surface charge.