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A heat-stable microparticle platform for oral micronutrient delivery.

  • Anselmo AC David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Xu X David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Buerkli S Institute of Food Nutrition and Health, ETH Zürich, Zürich 8092, Switzerland.
  • Zeng Y David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Tang W David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • McHugh KJ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Behrens AM David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Rosenberg E David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Duan AR David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Sugarman JL David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Zhuang J David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Collins J David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Lu X David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Graf T David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Tzeng SY David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Rose S David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Acolatse S David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Nguyen TD David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Le X David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Guerra AS Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
  • Freed LE David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Weinstock SB Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
  • Sears CB Independent Scholar, Belmont, MA 02478, USA.
  • Nikolic B Biomatics Capital, 1107 1st Avenue, Apartment 1305, Seattle, WA 98101, USA.
  • Wood L Institute for Disease Modeling, Bellevue, WA 98005, USA.
  • Welkhoff PA Institute for Disease Modeling, Bellevue, WA 98005, USA.
  • Oxley JD Southwest Research Institute, San Antonio, TX 78238, USA.
  • Moretti D Institute of Food Nutrition and Health, ETH Zürich, Zürich 8092, Switzerland.
  • Zimmermann MB Institute of Food Nutrition and Health, ETH Zürich, Zürich 8092, Switzerland.
  • Langer R David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. jaklenec@mit.edu rlanger@mit.edu.
  • Jaklenec A David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. jaklenec@mit.edu rlanger@mit.edu.
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  • 2019-11-15
Published in:
  • Science translational medicine. - 2019
Administration, Oral
Animals
Biological Availability
Biological Transport
Delayed-Action Preparations
Drug Liberation
Female
Hot Temperature
Humans
Hyaluronic Acid
Intestinal Absorption
Intestines
Iron
Methacrylates
Mice
Micronutrients
Microspheres
Oxidation-Reduction
Ultraviolet Rays
Vitamin A
Water
English Micronutrient deficiencies affect up to 2 billion people and are the leading cause of cognitive and physical disorders in the developing world. Food fortification is effective in treating micronutrient deficiencies; however, its global implementation has been limited by technical challenges in maintaining micronutrient stability during cooking and storage. We hypothesized that polymer-based encapsulation could address this and facilitate micronutrient absorption. We identified poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate) (1:2:1) (BMC) as a material with proven safety, offering stability in boiling water, rapid dissolution in gastric acid, and the ability to encapsulate distinct micronutrients. We encapsulated 11 micronutrients (iron; iodine; zinc; and vitamins A, B2, niacin, biotin, folic acid, B12, C, and D) and co-encapsulated up to 4 micronutrients. Encapsulation improved micronutrient stability against heat, light, moisture, and oxidation. Rodent studies confirmed rapid micronutrient release in the stomach and intestinal absorption. Bioavailability of iron from microparticles, compared to free iron, was lower in an initial human study. An organotypic human intestinal model revealed that increased iron loading and decreased polymer content would improve absorption. Using process development approaches capable of kilogram-scale synthesis, we increased iron loading more than 30-fold. Scaled batches tested in a follow-up human study exhibited up to 89% relative iron bioavailability compared to free iron. Collectively, these studies describe a broad approach for clinical translation of a heat-stable ingestible micronutrient delivery platform with the potential to improve micronutrient deficiency in the developing world. These approaches could potentially be applied toward clinical translation of other materials, such as natural polymers, for encapsulation and oral delivery of micronutrients.
Language
  • English
Open access status
bronze
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Persistent URL
https://folia.unifr.ch/global/documents/267701
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