Magnetically responsive polymeric microparticles for oral delivery of protein drugs.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Cheng
Jianjun
J
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA.
Teply
Benjamin A
BA
Jeong
Seok Yoon
SY
Yim
Christopher H
CH
Ho
Dennis
D
Sherifi
Ines
I
Jon
Sangyong
S
Farokhzad
Omid C
OC
Khademhosseini
Ali
A
Langer
Robert S
RS
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004574:Electromagnetic Fields; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D005772:Gastrointestinal Transit; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007408:Intestinal Absorption; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; D011506:Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D052203:Ferrosoferric Oxide