Abstract
PLGA microspheres are attractive DNA delivery vehicles due to their controlled release capabilities. One major problem with PLGA microspheres is that they develop an acidic microclimate as the polymer degrades, lowering the intraparticle pH, and potentially damaging the DNA. Antacids have recently shown promise in buffering this acidic microclimate and enhancing protein stability. We manufactured uniform plasmid DNA-encapsulating PLGA microspheres of two sizes (47, 80 μm diameter) and antacid concentrations (0, 3% Mg(OH)2). Microspheres with antacid had a homogeneous surface coverage of small pores, which resulted in a significant reduction of the burst effect. The 47 μm microspheres exhibited complete release of plasmid DNA over the course of two months. Incomplete release was observed from 80 μm spheres, though microspheres with 3% Mg(OH)2 showed a higher cumulative release, suggesting that the antacid at least partially aids in increasing the stability of DNA. SEM was used to visualize the surface pore evolution and cross-sectional microsphere structure over time. Subsequent image analysis was used to quantify the increase of surface pore sizes. Cross-sectional images showed increasing internal degradation and erosion, which resulted in a hollowing-out of microspheres. Our studies show that the incorporation of antacid into the microsphere structure has potential in addressing some of the major problems associated with DNA encapsulation and release in PLGA microspheres.
| Original language | English |
|---|---|
| Pages (from-to) | 172-180 |
| Number of pages | 9 |
| Journal | Journal of Controlled Release |
| Volume | 124 |
| Issue number | 3 |
| DOIs | |
| State | Published - Dec 20 2007 |
Bibliographical note
Funding Information:This research was sponsored by the National Institute of Health under NIH EB002878 and NIH EB005181. All scanning electron microscopy studies were carried out in 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.
Funding
This research was sponsored by the National Institute of Health under NIH EB002878 and NIH EB005181. All scanning electron microscopy studies were carried out in 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.
| Funders | Funder number |
|---|---|
| Italian National Health Institute | |
| National Institutes of Health (NIH) | EB005181 |
| Michigan State University-U.S. Department of Energy (MSU-DOE) Plant Research Laboratory | DEFG02-91-ER45439 |
| National Institute of Biomedical Imaging and Bioengineering | R21EB002878 |
Keywords
- DNA delivery
- Magnesium hydroxide
- Microspheres
- Plasmid DNA
- Poly (lactide-co-glycolide)
ASJC Scopus subject areas
- Pharmaceutical Science
