Abstract
In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization.
Highlights
One of the challenges of nanotechnology in the nutraceutical/food field is to improve the bioavailability of the nutritional components [1,2,3,4,5]
The liposomal-iron based products found in the scientific literature and those already present on the market show some failing in terms of formulation. They are frequently characterized by an unbalanced ascorbic acid/iron ratio or contain the less absorbable iron form [9,16,17], i.e., the most used product against anemia, sold under the trade name Sideral, contains iron microencapsulated in a lipid matrix, but in this case, the iron is in the oxidation state +3 (Fe (III))
The conventional ethanol injection (EI) and the thin film hydration (TFH) methods were adopted for the production of ferrous sulfate loaded nanoliposomes in order to have a comparison in terms of productivity with those achieved by the use of the SMF apparatus
Summary
One of the challenges of nanotechnology in the nutraceutical/food field is to improve the bioavailability of the nutritional components [1,2,3,4,5]. Many bioactive compounds are poorly absorbed and/or rapidly metabolized as soon as ingested and are not able to be absorbed in their active form Nanoscale delivery systems, such as nanoliposomes, can help to increase the bioavailability of active compounds, protecting them during the digestive process and, at the same time, improving their uptake in the gastro-intestinal tract [4,6,7,8]. The liposomal-iron based products found in the scientific literature and those already present on the market show some failing in terms of formulation They are frequently characterized by an unbalanced ascorbic acid/iron ratio or contain the less absorbable iron form [9,16,17], i.e., the most used product against anemia, sold under the trade name Sideral, contains iron microencapsulated in a lipid matrix, but in this case, the iron is in the oxidation state +3 (Fe (III)). In order to perform propaedeutic studies for the plant scale up, the possibility to produce liposomal structures using sonication batch with higher volumes was tested
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