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

Zandstra, J., van Beuge, M. M., Zuidema, J., Petersen, A. H., Staal, M., Duque, L. F., Rodriguez, S., Lathuile, A. A. R., Veldhuis, G. J., Steendam, R., Bank, R. A. & Popa, E. R., Oct-2015, In : Pharmaceutical Research. 32, 10, p. 3238-3247 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

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.

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.

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.

Original languageEnglish
Pages (from-to)3238-3247
Number of pages10
JournalPharmaceutical Research
Volume32
Issue number10
Publication statusPublished - Oct-2015

    Keywords

  • ischemia reperfusion, kidney, local drug delivery, microspheres, rapamycin, ACUTE KIDNEY INJURY, ISCHEMIA-REPERFUSION INJURY, IN-VITRO, SIROLIMUS, AUTOPHAGY, INFLAMMATION, TRANSPLANTATION, MACROPHAGES, REGULATORS, FIBROSIS

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