Surface-layer protein coated microspheres and uses thereof
The invention provides surface-layer protein coated microspheres for delivery of a therapeutic agent to the intestine. These surface-layer protein coated microspheres generally include a core encapsulated by a microsphere which is coated by surface layer protein. The core includes a therapeutic agent, such as a defensin. The invention also includes methods of making and using the surface-layer protein coated microspheres of the invention for administering therapeutic agents to a subject in need thereof. The invention also includes pharmaceutical dosage units that include the surface-layer protein coated microspheres of the invention. The invention further includes various labeled defensins for use in the study of the properties and actions of defensins, and further includes the use of defensins, particularly HD5α in the treatment of inflammatory conditions of the bowel, such as Crohn's disease.
1. A delivery device for administering a therapeutic agent to intestinal epithelium in a subject comprising:
a native defensin or analog thereof encapsulated in a biodegradable microsphere comprising poly(DL-lactide-co-glycolide); and
a coating attached to the biodegradable microsphere consisting of the bacterium surface layer protein SlpA purified from Lactobacillus brevis , wherein said SlpA is self-assembling, and has affinity for and is accessible for binding with the intestinal epithelium.
2. The delivery device of claim 1 wherein the defensin is HD5a or an analog thereof.
3. The delivery device of claim 1 , in a pharmaceutically acceptable carrier.
4. The delivery device claim 3 , wherein the device is provided in the form of a unitary dosage unit.
5. A method of preparing a delivery device for delivering a therapeutic agent to intestinal epithelium in a subject, the method comprising:
encapsulating a native defensin or analog thereof in a biodegradable microsphere comprising poly(DL-lactide-co-glycolide), and coating the biodegradable microsphere with an outer layer consisting of the bacterium surface layer protein SlpA purified from Lactobacillus brevis , wherein said bacterium surface layer protein is self-assembling, and has affinity for and is accessible for binding with the intestinal epithelium.
6. The method of claim 5 wherein the defensin is HD5a or an analog thereof.
7. A method of treating Crohn's disease comprising administering to a subject a pharmaceutical formulation comprising the delivery device of claim 1 .