A heat-stable microparticle platform for oral micronutrient delivery

Aaron C. Anselmo, Xian Xu, Simone Buerkli, Yingying Zeng, Wen Tang, Kevin J. McHugh, Adam M. Behrens, Evan Rosenberg, Aranda R. Duan, James L. Sugarman, Jia Zhuang, Joe Collins, Xueguang Lu, Tyler Graf, Stephany Y. Tzeng, Sviatlana Rose, Sarah Acolatse, Thanh D. Nguyen, Xiao Le, Ana Sofia GuerraLisa E. Freed, Shelley B. Weinstock, Christopher B. Sears, Boris Nikolic, Lowell Wood, Philip A. Welkhoff, James D. Oxley, Diego Moretti, Michael B. Zimmermann, Robert Langer, Ana Jaklenec

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Article numbereaaw3680
JournalScience translational medicine
Issue number518
StatePublished - Nov 13 2019

ASJC Scopus subject areas

  • Medicine(all)


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