Staff View: Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

Background and purpose: Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. Experimental approach: 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenou...

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Main Authors:	Chai, H.J., Kiew, L.V., Chin, Y., Norazit, A., Noor, S.M., Lo, Y.L., Looi, C.Y., Lau, Y.S., Lim, T.M., Wong, W.F., Abdullah, N.A., Sattar, M.Z.A., Johns, E.J., Chik, Z., Chung, L.Y.
Format:	Article
Published:	Dove Medical Press 2017
Subjects:	R Medicine
Online Access:	http://eprints.um.edu.my/19216/ http://dx.doi.org/10.2147/IJN.S111284
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spelling	my.um.eprints.192162018-09-13T03:41:27Z http://eprints.um.edu.my/19216/ Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats Chai, H.J. Kiew, L.V. Chin, Y. Norazit, A. Noor, S.M. Lo, Y.L. Looi, C.Y. Lau, Y.S. Lim, T.M. Wong, W.F. Abdullah, N.A. Sattar, M.Z.A. Johns, E.J. Chik, Z. Chung, L.Y. R Medicine Background and purpose: Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. Experimental approach: 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). Results: In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. Conclusion/Implications: The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier. Dove Medical Press 2017 Article PeerReviewed Chai, H.J. and Kiew, L.V. and Chin, Y. and Norazit, A. and Noor, S.M. and Lo, Y.L. and Looi, C.Y. and Lau, Y.S. and Lim, T.M. and Wong, W.F. and Abdullah, N.A. and Sattar, M.Z.A. and Johns, E.J. and Chik, Z. and Chung, L.Y. (2017) Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats. International Journal of Nanomedicine, 12. pp. 577-591. ISSN 1178-2013 http://dx.doi.org/10.2147/IJN.S111284 doi:10.2147/IJN.S111284
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine Chai, H.J. Kiew, L.V. Chin, Y. Norazit, A. Noor, S.M. Lo, Y.L. Looi, C.Y. Lau, Y.S. Lim, T.M. Wong, W.F. Abdullah, N.A. Sattar, M.Z.A. Johns, E.J. Chik, Z. Chung, L.Y. Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats
description	Background and purpose: Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. Experimental approach: 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). Results: In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. Conclusion/Implications: The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier.
format	Article
author	Chai, H.J. Kiew, L.V. Chin, Y. Norazit, A. Noor, S.M. Lo, Y.L. Looi, C.Y. Lau, Y.S. Lim, T.M. Wong, W.F. Abdullah, N.A. Sattar, M.Z.A. Johns, E.J. Chik, Z. Chung, L.Y.
author_facet	Chai, H.J. Kiew, L.V. Chin, Y. Norazit, A. Noor, S.M. Lo, Y.L. Looi, C.Y. Lau, Y.S. Lim, T.M. Wong, W.F. Abdullah, N.A. Sattar, M.Z.A. Johns, E.J. Chik, Z. Chung, L.Y.
author_sort	Chai, H.J.
title	Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats
title_short	Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats
title_full	Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats
title_fullStr	Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats
title_full_unstemmed	Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats
title_sort	renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats
publisher	Dove Medical Press
publishDate	2017
url	http://eprints.um.edu.my/19216/ http://dx.doi.org/10.2147/IJN.S111284
_version_	1643690921554870272
score	13.211869

Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

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