Nanoparticulate Delivery Can Improve Peroral Bioavailability of Cyclosporine and Match Neoral C_max Sparing the Kidney from Damage

Authors: Ankola, D.D.; Wadsworth, R.M.; Ravi Kumar, M.N.V.

Source: Journal of Biomedical Nanotechnology, Volume 7, Number 2, April 2011 , pp. 300-307(8)

Publisher: American Scientific Publishers

Buy & download fulltext article:

Price: $113.00 plus tax (Refund Policy)

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^®, 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 C_max of Neoral^® at 15 mg/Kg, which upon chronic administration over a period of 30 days daily dosing showed low nephrotoxicity to that exhibited by Neoral^®. 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.

Keywords: BIODEGRADABLE; BIOAVAILABILITY; NANOPARTICLES; NEPHROTOXICITY; ORAL DELIVERY

Document Type: Research article

DOI: http://dx.doi.org/10.1166/jbn.2011.1278

Publication date: 2011-04-01

More about this publication?

Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
Editorial Board
Information for Authors
Subscribe to this Title
Terms & Conditions
ingentaconnect is not responsible for the content or availability of external websites