Polymeric microspheres for the sustained release of a protein-based drug carrier targeting the PDGF β-receptor in the fibrotic kidney

Publication date: 20 December 2017 Source:International Journal of Pharmaceutics, Volume 534, Issues 1–2 Author(s): N. Teekamp, F. Van Dijk, A. Broesder, M. Evers, J. Zuidema, R. Steendam, E. Post, J.L. Hillebrands, H.W. Frijlink, K. Poelstra, L. Beljaars, P. Olinga, W.L.J. Hinrichs 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 14days. After subcutaneous administration to mice suffering from renal fibrosis pPB-HSA was released from the microspheres and distributed into ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research