Magnetically Responsive Polymeric Microparticles for Oral Delivery of Protein Drugs
Protein drugs cannot be delivered efficiently through oral routes. To address this challenge, we evaluated the effect of prolonged gastrointestinal transit on the bioavailability of insulin carried by magnetically responsive microparticles in the presence of an external magnetic field.
Magnetite nanocrystals and insulin were coencapsulated into poly(lactide-co-glycolide) (PLGA) microparticles and their effects on hypoglycemia were evaluated in mice in the presence of a circumferentially applied external magnetic field.
A single administration of 100 U/kg of insulin–magnetite–PLGA microparticles to fasted mice resulted in a reduction of blood glucose levels of up to 43.8% in the presence of an external magnetic field for 20 h (bioavailability = 2.77 ± 0.46 and 0.87 ± 0.29% based on glucose and ELISA assay, respectively), significantly higher than similarly dosed mice without a magnetic field (bioavailability = 0.66 ± 0.56 and 0.30 ± 0.06%, based on glucose and ELISA assay, respectively).
A substantially improved hypoglycemic effect was observed in mice that were orally administered with insulin–magnetite–PLGA microparticles in the presence of an external magnetic field, suggesting that magnetic force can be used to improve the efficiency of orally delivered protein therapeutics.
Key Wordsinsulin magnetic particles microparticles oral delivery protein drugs
The authors would like to thank Dr. George Kodokian, Dr. Hongming Chen, Dr. Daniel Kohane, Dr. Jeffrey Karp, and Dr. Yoon Yeo for their helpful discussions. This research was supported by the DuPont–MIT Alliance and the NIH. Ines Sherifi was financially supported by the University of Toronto.
- 9.Uchiyama, T., Sugiyama, T., Quan, Y. S., Kotani, A., Okada, N., Fujita, T., Muranishi, S., Yamamoto, A. 1999Enhanced permeability of insulin across the rat intestinal membrane by various absorption enhancers: their intestinal mucosal toxicity and absorption-enhancing mechanism of n-lauryl-beta-d-maltopyranosideJ. Pharm. Pharmacol.5112411250PubMedGoogle Scholar
- 19.Hovgaard, L., Jacobs, H., Wilson, D. E., Kim, S. W. 1996Stabilization of insulin by alkylmaltosides. B. Oral absorption in vivo in ratsInt. J. Pharm.132115121Google Scholar