TY - JOUR
T1 - A heat-stable microparticle platform for oral micronutrient delivery
AU - Anselmo, Aaron C.
AU - Xu, Xian
AU - Buerkli, Simone
AU - Zeng, Yingying
AU - Tang, Wen
AU - McHugh, Kevin J.
AU - Behrens, Adam M.
AU - Rosenberg, Evan
AU - Duan, Aranda R.
AU - Sugarman, James L.
AU - Zhuang, Jia
AU - Collins, Joe
AU - Lu, Xueguang
AU - Graf, Tyler
AU - Tzeng, Stephany Y.
AU - Rose, Sviatlana
AU - Acolatse, Sarah
AU - Nguyen, Thanh D.
AU - Le, Xiao
AU - Guerra, Ana Sofia
AU - Freed, Lisa E.
AU - Weinstock, Shelley B.
AU - Sears, Christopher B.
AU - Nikolic, Boris
AU - Wood, Lowell
AU - Welkhoff, Philip A.
AU - Oxley, James D.
AU - Moretti, Diego
AU - Zimmermann, Michael B.
AU - Langer, Robert
AU - Jaklenec, Ana
N1 - Publisher Copyright:
© 2019 The Authors.
PY - 2019/11/13
Y1 - 2019/11/13
N2 - 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.
AB - 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.
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U2 - 10.1126/scitranslmed.aaw3680
DO - 10.1126/scitranslmed.aaw3680
M3 - Article
C2 - 31723037
AN - SCOPUS:85074960765
SN - 1946-6234
VL - 11
JO - Science translational medicine
JF - Science translational medicine
IS - 518
M1 - eaaw3680
ER -