Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

Autor: Zandstra J; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., van Beuge MM; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. m.m.van.beuge@umcg.nl., Zuidema J; InnoCore Pharmaceuticals, Groningen, The Netherlands., Petersen AH; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Staal M; InnoCore Pharmaceuticals, Groningen, The Netherlands., Duque LF; InnoCore Pharmaceuticals, Groningen, The Netherlands., Rodriguez S; Nanomi BV, Oldenzaal, The Netherlands., Lathuile AA; Nanomi BV, Oldenzaal, The Netherlands., Veldhuis GJ; Nanomi BV, Oldenzaal, The Netherlands., Steendam R; InnoCore Pharmaceuticals, Groningen, The Netherlands., Bank RA; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Popa ER; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2015 Oct; Vol. 32 (10), pp. 3238-47. Date of Electronic Publication: 2015 May 09.
DOI: 10.1007/s11095-015-1700-8
Abstrakt: Purpose: The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney.
Methods: We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs. Using a rat model of acute kidney injury, subcapsular injection of placebo and rapamycin monodisperse microspheres (monospheres) was compared to subcutaneous injection, mimicking systemic administration.
Results: We did not find any adverse effects related to the delivery method. Irrespective of the injection site, a similar low dose of rapamycin was present in the circulation. However, only local intrarenal delivery of rapamycin from monospheres led to decreased macrophage infiltration and a significantly lower amount of myofibroblasts in the kidney, where systemic administration did not. Local delivery of rapamycin did cause a transient increase in the deposition of collagen I, but not of collagen III.
Conclusions: We conclude that therapeutic effects can be increased when rapamycin is delivered subcapsularly by monospheres, which, combined with low systemic concentrations, may lead to an effective intrarenal delivery method.
Databáze: MEDLINE
Externí odkaz: