Biodegradable Nanoparticles for Protein Delivery: Analysis of Preparation Conditions on Particle Morphology and Protein Loading, Activity and Sustained Release Properties
Coleman, J; Lowman, A
| HERO ID | 1292895 |
|---|---|
| In Press | No |
| Year | 2012 |
| Title | Biodegradable Nanoparticles for Protein Delivery: Analysis of Preparation Conditions on Particle Morphology and Protein Loading, Activity and Sustained Release Properties |
| Authors | Coleman, J; Lowman, A |
| Journal | Journal of Biomaterials Science, Polymer Edition |
| Volume | 23 |
| Issue | 9 |
| Page Numbers | 1129-1151 |
| Abstract | PLGA particles have been extensively used as a sustained drug-delivery system, but there are multiple drawbacks when delivering proteins. The focus of this work is to address the most significant disadvantages to the W/O/W double emulsion procedure and demonstrate that simple changes to this procedure can have significant changes to particle size and dispersity and considerable improvements to protein loading, activity and sustained active protein release. A systematic approach was taken to analyze the effects of the following variables: solvent miscibility (dichloromethane (DCM), ethyl acetate, acetone), homogenization speed (10 000-25 000 rpm), PLGA concentration (10-30 mg/ml) and additives in both the organic (sucrose acetate isobutyrate (SAIB)) and aqueous (bovine serum albumin (BSA)) phases. Increasing solvent miscibility decreased particle size, dispersity and protein denaturation, while maintaining adequate protein loading. Increasing solvent miscibility also lowered the impact of homogenization on particle size and dispersity and protein activity. Changes to PLGA concentration demonstrated a minimum impact on particle size and dispersity, but showed an inverse relationship between protein encapsulation efficiency and particle protein weight percent. Most particles tested provided sustained release of active protein over 60 days. Increasing solvent miscibility resulted in increases in the percent of active protein released. When subjected to synthesis conditions with DCM as the solvent, BSA as a stabilizer resulted in the maximum stabilization of protein at a concentration of 100 mg/ml. At this concentration, BSA allowed for increases in the total amount of active protein delivered for all three solvents. The benefit of SAIB was primarily increased protein loading. |
| Doi | 10.1163/092050611X576648 |
| Pmid | 21639993 |
| Wosid | WOS:000307445200001 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science 000307445200001 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Water/oil/water (W/O/W); protein delivery; poly(lactide-co-glycolide) (PLGA); spinal cord injury; lysozyme; nanoparticles |