A Nanocomposite Vehicle Based on Metal–Organic Framework Nanoparticle Incorporated Biodegradable Microspheres for Enhanced Oral Insulin Delivery

Citations Over TimeTop 10% of 2020 papers

Abstract

Oral insulin delivery has revolutionized diabetes treatment, but challenges including degradation in the gastrointestinal environment and low permeation across the intestinal epithelium remain. Herein, to overcome these barriers, we developed a novel biodegradable nanocomposite microsphere embedded with metal-organic framework (MOF) nanoparticles. An iron-based MOF nanoparticle (NP) (MIL-100) was first synthesized as a carrier with an insulin loading capacity of 35%. The insulin-loaded MIL-100 nanoparticles modified with sodium dodecyl sulfate (Ins@MIL100/SDS) promoted insulin permeation across Caco-2 monolayer models in vitro. To improve resistance to the gastric acid environment, Ins@MIL100/SDS nanoparticles were embedded into a biodegradable microsphere to construct the nanocomposite delivery system (Ins@MIL100/SDS@MS). The microspheres effectively protected the MOF NPs from rapid degradation under acidic conditions and could release insulin-loaded MOF NPs in the simulated intestinal fluid. After the oral administration of Ins@MIL100/SDS@MS into BALB/c nude mice, increased intestinal absorption of the insulin was detected compared to the oral administration of free insulin or Ins@MIL100/SDS. Furthermore, significantly enhanced plasma insulin levels were obtained for over 6 h after oral administration of Ins@MIL100/SDS@MS into diabetic rats, leading to a remarkably enhanced effect in lowering blood glucose level with a relative pharmacological availability of 7.8%. Thus, the MOF-nanoparticle-incorporated microsphere may provide a new strategy for effective oral protein delivery.

Related Papers

• → Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine(1988)341 cited
• → Repeated oral administration modulates the pharmacokinetic behavior of the chemopreventive agent phenethyl isothiocyanate in rats(2009)37 cited
• → Bioavailability and first‐pass metabolism of oral pentazocine in man(1977)64 cited
• → Enhanced Oral Bioavailability of DDI After Administration of 6-Cl-ddP, an Adenosine Deaminase-Activated Prodrug, to Chronically Catheterized Rats(1995)20 cited
• → Pharmacokinetics of a Micronized, Poorly Water-Soluble Drug, HO-221, in Experimental Animals.(1993)18 cited