Research ArticleDrug Delivery

A heat-stable microparticle platform for oral micronutrient delivery

See allHide authors and affiliations

Science Translational Medicine  13 Nov 2019:
Vol. 11, Issue 518, eaaw3680
DOI: 10.1126/scitranslmed.aaw3680

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Mitigating micronutrient deficiency

Particularly within the developing world, micronutrient deficiencies that impair growth and contribute to disease remain leading public health concerns. Although fortification of food can help treat deficiencies, heat used during cooking and other conditions can degrade vitamins, preventing adequate absorption. Anselmo and colleagues used the polymer BMC to encapsulate micronutrients. Microparticles encapsulating 11 micronutrients showed improved stability against oxidation, heat (such as boiling water used for cooking), and other conditions, and micronutrients were absorbed by the intestine when microparticles were administered to rodents. Data from two clinical trials and experiments using human intestinal tissue demonstrate how microparticle formulations were optimized to enhance iron loading, improve bioavailability, retain stability against cooking, and allow for scale-up. This microparticle platform could help improve oral delivery of micronutrients.

Abstract

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.

View Full Text