Desenvolvimento e caracterização de nanoemulsão lipídica com potencial para aplicação na Nutrição Parenteral

Abstract

Parenteral Nutrition (PN) consists of the intravenous infusion of nutrients. In PN, fatty acids (FA) are supplied through parenteral lipid emulsions (PLE). It is worth noting that parenteral lipid nanoemulsions are a type of PLE that have smaller particle sizes. The current market need is to expand and diversify the composition and availability of alternative PLE that are anti-inflammatory. The objective of this study was to develop and characterize stable lipid emulsions with potential for application in Parenteral Nutrition. To this end, the research was structured in four phases. In the first phase, a technological prospecting was carried out in the patent databases of Espacenet and PatentScope to map and identify oils with potential application in PN. Subsequently, in the second phase, a scientific survey was carried out in the MEDLINE, Web of Science and Scopus databases to evaluate the most recent scientific evidence on the application of lipid emulsion in PN. The third and fourth phases were characterized by the preparation of emulsions using microfluidization. In this sense, the third phase consisted of conducting a pilot experiment that assisted the fourth phase, so that the emulsion with sesame oil was developed to determine the ranges of the experimental parameters of the equipment and emulsifier used. The fourth phase involved conducting a complete factorial design 22 with three central points, having as independent variables: Pressure (PR; 20,000 or 30,000 psi) and Cycle (CL; 4 or 10n). Seven formulations were obtained adopting a fixed concentration of 20% of three different types of oils (10g of sesame oil, 5g of linseed oil and 5g of peanut oil). The criterion adopted in the selection process of the mentioned oils was based on the fatty acid profile and the bioactive properties in the human body. The formulations were characterized by visual inspection, particle size (nm), polydispersity index, zeta potential (mV), and pH. Based on the characterization data, the best formulation was identified and additional analyses were performed on the D0 and D30 formulations under different storage temperature conditions (4°C, 25°C, and 40°C). Additional analyses included viscosity (cP), osmolarity (mOsm/kg), fatty acid profile (%), sterility analysis, and endotoxin. Regarding the results of the technological prospecting, it was identified that soybean oil is the most widely used oil for the manufacture of lipid emulsions applied to PN in the world, and the related patented technology is concentrated in developed countries, such as the United States and China. The most recent scientific evidence on the application of lipid emulsions in PN reveals that fish oil-based emulsions have a positive impact on the patient's clinical condition when compared to other emulsion formulations. However, there are few studies to obtain a definitive conclusion about the superiority of one formulation over another. The emulsions developed with sesame oil establish that the pressure range (PR; 20,000 or 30,000 psi), cycle (CL; 4 or 10n) and 1.2g lecithin promoted results in accordance with the pharmacopoeia. The emulsions formulated with sesame, linseed and peanut oil presented homogeneous appearance and milky white coloration, particle size (197.47 -292.47nm), PDI of (0.06 - 0.11), zeta potential of (-26.42 to -40.92mV) and pH values of (7.87 - 8.56). The analyses of the parameters of the dependent variables on the independent variables from the evaluation of the Pareto charts and Response Surfaces in the experimental design indicated that the best condition of process parameters for the development of emulsions was PR (25,000 psi) and CL (n 7). The complementary analyses performed on the best formulation indicated adequate osmolarity and viscosity immediately after production and after one month of storage. Furthermore, the best formulation presented a high content of essential polyunsaturated fatty acids (α-linolenic fatty acid 12.63%; linoleic fatty acid 28.61%) and a high content of oleic acid 39.75%, thus indicating a formulation with potential to be anti-inflammatory. The monitoring of the microbiological control of the emulsions indicated that the formulations remained sterile and free of endotoxin during the investigation. The results of this study show a clear potential for the production of emulsions based on sesame, linseed and peanut oil. The developed formulations presented adequate physicochemical stability parameters when evaluated for one month. In addition, the particle sizes were within a range that can classify the developed emulsion as a nanoemulsion. Finally, the developed nanoemulsions have the potential to be alternative intravenous lipid nanoemulsions in the future.