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Adv Healthc Mater. 2018 Aug;7(16):e1800263. doi: 10.1002/adhm.201800263. Epub 2018 Jul 4.

Microparticles Locally Deliver Active Interleukin-1 Receptor Antagonist In Vivo.

Author information

1
University of Wisconsin, Madison, 1111 Highland Ave., 5405 WIMR II, Madison, WI, 53705, USA.

Abstract

Despite significant research in therapeutic protein delivery, localized and sustained delivery of active therapeutic proteins remains a challenge. Delivery is a particular challenge for therapeutic proteins with a short half-life. Herein, localized delivery of interleukin-1 receptor antagonist (IL-1Ra) by mineral coated microparticles (MPs) is assessed in a healing rat medial collateral ligament (MCL). The local tissue concentration and systemic serum concentration of IL-1Ra, the anti-inflammatory activity of IL-1Ra delivered with MPs, and whether IL-1Ra loaded MPs (IL-1Ra MPs) are immunogenic in a healing ligament are also examined. IL-1Ra MPs significantly increase the local concentration of IL-1Ra compared to soluble IL-1Ra at 7 and 14 days after treatment but do not elevate the systemic concentration of IL-1Ra at these time points, indicating localized delivery of IL-1Ra. IL-1Ra MPs significantly reduce inflammation caused by the MPs themselves, indicating the IL-1Ra is active. Finally, IL-1Ra MPs do not induce a foreign body response and decrease the immunogenicity of human IL-1Ra in a healing rat MCL. Overall, mineral coated microparticles have the ability to locally deliver active therapeutic proteins for an extended period of time.

KEYWORDS:

interleukin-1 receptor antagonist; localized protein delivery; microparticles; sustained delivery; therapeutic protein delivery

PMID:
29974661
DOI:
10.1002/adhm.201800263

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