Polymeric microspheres for the sustained release of a protein-based drug carrier targeting the PDGFβ-receptor in the fibrotic kidneyTeekamp, N., Van Dijk, F., Broesder, A., Evers, M., Zuidema, J., Steendam, R., Post, E., Hillebrands, J. L., Frijlink, H. W., Poelstra, K., Beljaars, L., Olinga, P. & Hinrichs, W. L. J., 20-Dec-2017, In : International Journal of Pharmaceutics. 534, 1-2, p. 229-236 8 p.
Research output: Contribution to journal › Article › Academic › peer-review
- Pharmaceutical Technology and Biopharmacy
- Pharmacokinetics, Toxicology and Targeting
- Groningen Kidney Center (GKC)
- Vascular Ageing Programme (VAP)
- Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
- Science and Engineering Faculty Board
- Nanobiotechnology and Advanced Therapeutic Materials (NANOBIOMAT)
- Groningen Institute for Organ Transplantation (GIOT)
Injectable sustained release drug delivery systems are an attractive alternative for the intravenous delivery of therapeutic proteins. In particular, for chronic diseases such as fibrosis, this approach could improve therapy by reducing the administration frequency while avoiding large variations in plasma levels. In fibrotic tissues the platelet-derived growth factor receptor beta (PDGFβR) is highly upregulated, which provides a target for site-specific delivery of drugs. Our aim was to develop an injectable sustained release formulation for the subcutaneous delivery of the PDGFβR-targeted drug carrier protein pPB-HSA, which is composed of multiple PDGFβR-recognizing moieties (pPB) attached to human serum albumin (HSA). We used blends of biodegradable multi-block copolymers with different swelling degree to optimize the release rate using the model protein HSA from microspheres produced via a water-in-oil-in-water double emulsion evaporation process. The optimized formulation containing pPB-HSA, showed complete release in vitro within 14 days. After subcutaneous administration to mice suffering from renal fibrosis pPB-HSA was released from the microspheres and distributed into plasma for at least 7days after administration. Furthermore, we demonstrated an enhanced accumulation of pPB-HSA in the fibrotic kidney. Altogether, we show that subcutaneously administered polymeric microspheres present a suitable sustained release drug delivery system for the controlled systemic delivery for proteins such as pPB-HSA.
|Number of pages||8|
|Journal||International Journal of Pharmaceutics|
|Publication status||Published - 20-Dec-2017|
- Controlled release, Polymer drug delivery system, Protein delivery, Targeted drug delivery, Drug carrier, Renal fibrosis, HEPATIC STELLATE CELLS, DELIVERY, MICROPARTICLES, MECHANISMS, PEPTIDES, IMPLANTS, FIBROSIS, PLGA