Encapsulation of P-glycoprotein inhibitors by polymeric micelles can reduce their pharmacokinetic interactions with doxorubicin

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Ziyad BinkhathlanAfsaneh Lavasanifar

Abstract

Co-administration of P-glycoprotein (P-gp) inhibitors such as cyclosporine A (CyA) and its analogue valspodar with doxorubicin (DOX) can result in diminished clearance of DOX, leading to accentuated toxicity. The purpose of this study was to evaluate whether the effect of these P-gp inhibitors on the pharmacokinetics of DOX can be avoided through their encapsulation in polymeric micelles. Cyclosporine A or valspodar was physically encapsulated in methoxypoly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL) micelles using co-solvent evaporation method. The commercially available DOX was administered as a single dose of 5mg/kg intravenously to Sprague-Dawley rats either alone or 30min following a single intravenous dose (10mg/kg) of either CyA or valspodar as part of conventional or polymeric micellar formulation. Co-administration of DOX with either Sandimmune® or valspodar in the conventional Cremophor EL-based formulation was associated with greater than 50% reduction in DOX clearance (CL). Although there was nearly 40% reduction in the CL of DOX with the polymeric micellar formulation of CyA, there was only 6% reduction in CL of DOX upon co-administration with the polymeric micellar formulation of valspodar. In conclusion, ...Continue Reading

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Citations

Dec 2, 2014·International Journal of Pharmaceutics·Manu Smriti Singh, Alf Lamprecht
Jun 27, 2013·Biotechnology Advances·Manju Saraswathy, Shaoqin Gong
May 16, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Manu Smriti SinghAlf Lamprecht
May 28, 2016·Journal of Nanobiotechnology·Ewelina PiktelRobert Bucki
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Jul 18, 2020·Oncology Reviews·Sonu Kumar GuptaMalkhey Verma

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European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Ziyad BinkhathlanAfsaneh Lavasanifar
Journal of Controlled Release : Official Journal of the Controlled Release Society
Hamidreza Montazeri AliabadiAfsaneh Lavasanifar
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