Novel macromolecular therapeutics such as peptides, proteins, and DNA are advancing rapidly toward the clinic. Because of typically low oral bioavailability, macromolecule delivery requires invasive methods such as frequently repeated injections. Parenteral depots including biodegradable polymer microspheres offer the possibility of reduced dosing frequency but are limited by the inability to adequately control delivery rates. To control release and investigate release mechanisms, we have encapsulated model macromolecules in monodisperse poly(D,L-lactide-co-glycolide) (PLG) microspheres using a double-emulsion method in combination with the precision particle fabrication technique. We encapsulated fluorescein-dextran (F-Dex) and sulforhodamine B-labeled bovine serum albumin (R-BSA) into PLG microspheres of three different sizes: 31, 44, and 80 pm and 34, 47, and 85 μm diameter for F-Dex and R-BSA, respectively. The in vitro release profiles of both compounds showed negligible initial burst. During degradation and release, the microspheres hollowed and swelled at critical time points dependant upon microsphere size. The rate of these events increased with microsphere size resulting in the largest microspheres exhibiting the fastest overall release rate. Monodisperse microspheres may represent a new delivery system for therapeutic proteins and DNA and provide enhanced control of delivery rates using simple injectable depot formulations.
|Number of pages||16|
|Journal||Journal of Pharmaceutical Sciences|
|State||Published - May 2007|
Bibliographical noteFunding Information:
This work was supported in part by NIH Grant EB002878. Scanning electron micrographs were obtained at the Center for Microanalysis of Materials, University of Illinois, which is partially supported by the U.S. Department of Energy under grant DEFG02-91-ER45439.
- Bovine serum albumin
- Controlled release
- Uniform microspheres
ASJC Scopus subject areas
- Pharmaceutical Science