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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

Strathprints serves world leading Open Access research by the University of Strathclyde, including research by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), where research centres such as the Industrial Biotechnology Innovation Centre (IBioIC), the Cancer Research UK Formulation Unit, SeaBioTech and the Centre for Biophotonics are based.

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Nanoparticulate delivery can improve peroral bioavailability of cyclosporine and match neoral C-max sparing the kidney from damage

Ankola, D. D. and Wadsworth, R. M. and Kumar, M. N. V. Ravi (2011) Nanoparticulate delivery can improve peroral bioavailability of cyclosporine and match neoral C-max sparing the kidney from damage. Journal of Biomedical Nanotechnology, 7 (2). pp. 300-307. ISSN 1550-7033

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Abstract

Cyclosporine (CsA) as an immunosuppressant has demonstrated immense potential in the field of organ transplantation and autoimmune disorders, despite the nephrotoxicity. The present investigation is an attempt to develop biodegradable nanoparticles entrapping CsA that can match C-max of Neoral (R), the most potent formulation available to date. The C-max and AUC(0-72) of CsA administered as nanoparticles demonstrated an increase with increase in the dose administered, however the relative bioavailability decreased. The C-max and AUC(0-72) increased from 682 to 1073 ng/ml and 34854 to 55322 ng . h/ml, respectively whereas, the relative bioavailability decreased from 120 to 64%. On the other hand, the increase in initial CsA loading (10-30% w/w of polymer) recorded a proportional increase in C-max and AUC(0-72), from 494 to 1101 ng/ml and 17774 to 51763 ng . h/ml, respectively. The relative bioavailability also increased from 31 to 89%. The CsA nanoparticles at 30% CsA loading w/w of polymer and at 30 mg/Kg single dose demonstrated comparable Cmax of Neoral (R) at 15 mg/Kg, which upon chronic administration over a period of 30 days daily dosing showed low nephrotoxicity to that exhibited by Neoral (R). The reduced toxicity of nanoparticulate CsA indicated by lower blood urea nitrogen, plasma creatinine and glomerular damage, was due to delay in T-max as result of slow release of the CsA from the nanoparticles. The investigation unlocks the potential of polymeric nanoparticles in oral delivery of CsA.