Thermal protection and pH-gated release of folic acid in microparticles and nanoparticles for food fortification.

Encapsulation provides efficient approaches to increase stability and delivery of poorly soluble bioactive components, predominantly for fortification of beverages and similar liquid-based foods. In this study, folic acid was encapsulated within conventional and emulsion-templated alginate-pectin hydrogels, proliposomes, and a combination thereof. The stability of these systems was examined under various environmental conditions (pH 1.2-9.0, 25-85 °C, dark/light). The techniques demonstrated efficient and relatively straightforward production of well-defined microparticles and nanoparticles (350 nm to 250 μm). Dispersed folic acid provided a delivery system with unique pH-responsive features, which offered prolonged stability during food storage, and indicated increased release at the site of absorption upon ingestion. This formulation had no limitation due to particle size, while at the same time it allowed high encapsulation efficiencies (80%-100%), as compared to the low encapsulation efficiency achieved by solubilisation (6%). At the low pH that is expected in the stomach, leaching of the dispersed folic acid was prevented, while at the pH that is expected in the intestine, there was complete release via solubilisation and carrier swelling. Overall, the optimum for food processing and storage was pH 3.0, where ≥70% of 50% to 200% of the recommended daily allowance of folic acid remained in the alginate-pectin beads after 6 months at room temperature in the dark. The thermal properties were enhanced by emulsion-templated alginate-pectin beads and proliposomes. In this way, 30% to 75% retention of folic acid was achieved at temperatures ≤90 °C, where the proliposomes reinforced within a polysaccharide network achieved the highest level of protection.

[1]  K. Skryplonek,et al.  Probiotic fermented beverages based on acid whey. , 2019, Journal of dairy science.

[2]  D. Camacho,et al.  Encapsulation of folic acid in copper-alginate hydrogels and it's slow in vitro release in physiological pH condition. , 2019, Food research international.

[3]  J. V. van Gool,et al.  Folic acid and primary prevention of neural tube defects: A review. , 2018, Reproductive toxicology.

[4]  Xiuhua Wang,et al.  Design and intestinal mucus penetration mechanism of core‐shell nanocomplex , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[5]  Elisabete Pinto,et al.  The impact of folic acid supplementation on gestational and long term health: Critical temporal windows, benefits and risks , 2017, Porto biomedical journal.

[6]  T. Tian,et al.  Folic Acid Supplementation for Stroke Prevention in Patients With Cardiovascular Disease , 2017, The American journal of the medical sciences.

[7]  N. P. Ulrih,et al.  Encapsulation of pantothenic acid into liposomes and into alginate or alginate–pectin microparticles loaded with liposomes , 2017, Journal of Food Engineering.

[8]  S. Mordon,et al.  Stability of folic acid under several parameters. , 2016, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[9]  N. Poklar Ulrih,et al.  Encapsulation of (-)-epigallocatechin gallate into liposomes and into alginate or chitosan microparticles reinforced with liposomes. , 2016, Journal of the science of food and agriculture.

[10]  S. Jafari,et al.  Evaluation of Folic Acid Nano-encapsulation by Double Emulsions , 2016, Food and Bioprocess Technology.

[11]  I. Rosenberg,et al.  Excessive folic acid intake and relation to adverse health outcome. , 2016, Biochimie.

[12]  Guilherme M. Tavares,et al.  Spontaneous co-assembly of lactoferrin and β-lactoglobulin as a promising biocarrier for vitamin B9 , 2016 .

[13]  S. Jafari,et al.  Optimization of folic acid nano-emulsification and encapsulation by maltodextrin-whey protein double emulsions. , 2016, International journal of biological macromolecules.

[14]  J. Ruby,et al.  The pH of beverages in the United States. , 2016, Journal of the American Dental Association.

[15]  J. Lagarón,et al.  Photoprotection of folic acid upon encapsulation in food-grade amaranth (Amaranthus hypochondriacus L.) protein isolate – Pullulan electrospun fibers , 2015 .

[16]  Yuanlie Yu,et al.  Separation of monodisperse alginate nanoparticles and effect of particle size on transport of vitamin E. , 2015, Carbohydrate polymers.

[17]  C. Chiang,et al.  Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis. , 2015, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[18]  G. Ros,et al.  Encapsulation of folic acid in food hydrocolloids through nanospray drying and electrospraying for nutraceutical applications. , 2015, Food chemistry.

[19]  Carmen Alvarez-Lorenzo,et al.  Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery. , 2013, Advanced drug delivery reviews.

[20]  M. Edirisinghe,et al.  Application of Electrohydrodynamic Technology for Folic Acid Encapsulation , 2013, Food and Bioprocess Technology.

[21]  L. Sagis,et al.  Alginate submicron beads prepared through w/o emulsification and gelation with CaCl2 nanoparticles , 2013 .

[22]  D. Kitts,et al.  Microencapsulation of L-5-methyltetrahydrofolic acid with ascorbate improves stability in baked bread products. , 2013, Journal of agricultural and food chemistry.

[23]  A. Shojaei,et al.  Submicron nanoporous polyacrylamide beads with tunable size for verapamil imprinting , 2012 .

[24]  L. Mattoso,et al.  N,N,N-trimethyl chitosan nanoparticles as a vitamin carrier system , 2012 .

[25]  J. Arcot,et al.  Susceptibility of 5-methyltetrahydrofolic acid to heat and microencapsulation to enhance its stability during extrusion processing , 2012 .

[26]  G. Amidon,et al.  Physiological parameters for oral delivery and in vitro testing. , 2010, Molecular pharmaceutics.

[27]  Chunyan Hou,et al.  Solubility of Folic Acid in Water at pH Values between 0 and 7 at Temperatures (298.15, 303.15, and 313.15) K , 2010 .

[28]  M. Lucock,et al.  Folic acid fortification: a double-edged sword , 2009, Current opinion in clinical nutrition and metabolic care.

[29]  N. Muangsin,et al.  Ethyl Cellulose Microcapsules for Protecting and Controlled Release of Folic Acid , 2009, AAPS PharmSciTech.

[30]  A. Gliszczyńska-Świgło,et al.  pH-Dependent radical scavenging activity of folates. , 2007, Journal of agricultural and food chemistry.

[31]  E. Siebelink,et al.  Bioavailability of food folates is 80% of that of folic acid. , 2007, The American journal of clinical nutrition.

[32]  Edward Reynolds,et al.  Vitamin B12, folic acid, and the nervous system , 2006, The Lancet Neurology.

[33]  A. Gliszczyńska-Świgło Antioxidant activity of water soluble vitamins in the TEAC (trolox equivalent antioxidant capacity) and the FRAP (ferric reducing antioxidant power) assays , 2006 .

[34]  M. Phillips,et al.  Evaluation of alginate–pectin capsules in Cheddar cheese as a food carrier for the delivery of folic acid , 2006 .

[35]  J. Moan,et al.  Ultraviolet photodegradation of folic acid. , 2005, Journal of photochemistry and photobiology. B, Biology.

[36]  M. Phillips,et al.  Alginate–pectin microcapsules as a potential for folic acid delivery in foods , 2005, Journal of microencapsulation.

[37]  F. Rébeillé,et al.  Folic acid and folates: the feasibility for nutritional enhancement in plant foods , 2000 .

[38]  F. Gabreëls,et al.  A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? , 1998, American journal of human genetics.

[39]  M. Gnant,et al.  Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study , 1991, The Lancet.

[40]  W. Williams,et al.  A Simple Method for the Preparation of Liposomes for Pharmaceutical Applications: Characterization of the Liposomes , 1991, The Journal of pharmacy and pharmacology.

[41]  F. Bendtsen,et al.  Intraluminal pH in the stomach, duodenum, and proximal jejunum in normal subjects and patients with exocrine pancreatic insufficiency. , 1986, Gastroenterology.

[42]  I. Andresen,et al.  Temperature dependence of the elastic properties of alginate gels , 1977 .

[43]  Reynolds Eh The neurology of folic acid deficiency. , 2014 .

[44]  Maurice E. Shils,et al.  Modern Nutrition in Health and Disease , 1965, Diabetes.