Sustained protein release from hydrogel microparticles using layer-by-layer (LbL) technology.
- Sakr OS a School of Pharmaceutical Sciences Geneva-Lausanne, University of Geneva, University of Lausanne , Geneva , Switzerland.
- Jordan O a School of Pharmaceutical Sciences Geneva-Lausanne, University of Geneva, University of Lausanne , Geneva , Switzerland.
- Borchard G a School of Pharmaceutical Sciences Geneva-Lausanne, University of Geneva, University of Lausanne , Geneva , Switzerland.
- 2015-08-21
Published in:
- Drug delivery. - 2016
Layer-by-layer
lysozyme
protein activity
protein delivery
sustained delivery
Chemistry, Pharmaceutical
Coated Materials, Biocompatible
Delayed-Action Preparations
Drug Delivery Systems
Excipients
Hydrogel, Polyethylene Glycol Dimethacrylate
Muramidase
Polymers
Proteins
Technology, Pharmaceutical
English
CONTEXT AND OBJECTIVES
Since most of developed therapeutic proteins are intended to treat chronic diseases, patients are prescribed multiple injections for long time periods, and therefore, sustained release formulations are much needed. However, challenges facing these formulations are quite significant. In this context, a model protein, lysozyme (Lys), was loaded on hydrogel microparticles (beads) and the ability of layer-by-layer (LbL) coating to control Lys release and maintain its activity over a one-month period was investigated.
METHODS
LbL coating was composed of chondroitin sulfate as a negatively charged polyelectrolyte and a biocompatible, hydrolytically degradable poly β-aminoester as a positively charged polyelectrolyte. Loading distribution was monitored by fluorescence imaging, and followed by depositing a series of LbL coatings of different thicknesses. Release of Lys from these formulations was studied and activity of released fraction was determined.
RESULTS
Lys was loaded effectively on hydrogel beads achieving about 9 mg protein/100 mg wet spheres. LbL coating was proven successful by monitoring the zeta potential of the beads, which was reversed after the addition of each layer. In vitro release studies showed sustained release profiles that depend on the thickness of the deposited coat, with t50 extended from 4.9 to 143.9 h. More importantly, released Lys possessed a high degree of biological activity during the course of release maintaining at least 72% of initial activity.
CONCLUSIONS
Successful loading of Lys and extension of its release while maintaining a considerable degree of activity might make this formulation suitable for use with other active therapeutic proteins.
Since most of developed therapeutic proteins are intended to treat chronic diseases, patients are prescribed multiple injections for long time periods, and therefore, sustained release formulations are much needed. However, challenges facing these formulations are quite significant. In this context, a model protein, lysozyme (Lys), was loaded on hydrogel microparticles (beads) and the ability of layer-by-layer (LbL) coating to control Lys release and maintain its activity over a one-month period was investigated.
METHODS
LbL coating was composed of chondroitin sulfate as a negatively charged polyelectrolyte and a biocompatible, hydrolytically degradable poly β-aminoester as a positively charged polyelectrolyte. Loading distribution was monitored by fluorescence imaging, and followed by depositing a series of LbL coatings of different thicknesses. Release of Lys from these formulations was studied and activity of released fraction was determined.
RESULTS
Lys was loaded effectively on hydrogel beads achieving about 9 mg protein/100 mg wet spheres. LbL coating was proven successful by monitoring the zeta potential of the beads, which was reversed after the addition of each layer. In vitro release studies showed sustained release profiles that depend on the thickness of the deposited coat, with t50 extended from 4.9 to 143.9 h. More importantly, released Lys possessed a high degree of biological activity during the course of release maintaining at least 72% of initial activity.
CONCLUSIONS
Successful loading of Lys and extension of its release while maintaining a considerable degree of activity might make this formulation suitable for use with other active therapeutic proteins.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.3109/10717544.2015.1069422
- PMID 26289209
- Persistent URL
- https://sonar.ch/global/documents/88148
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