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

Hann-Juang Chai,1 Lik-Voon Kiew,1 Yunni Chin,1 Anwar Norazit,2 Suzita Mohd Noor,2 Yoke-Lin Lo,3,4 Chung-Yeng Looi,1 Yeh-Siang Lau,1 Tuck-Meng Lim,5 Won-Fen Wong,6 Nor Azizan Abdullah,1 Munavvar Zubaid Abdul Sattar,7 Edward J Johns,8 Zamri Chik,1 Lip-Yong Chung3 1Department of Pharmacology, 2Departm...

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Autores principales:	Chai HJ, Kiew LV, Chin Y, Norazit A, Mohd Noor S, Lo YL, Looi CY, Lau YS, Lim TM, Wong WF, Abdullah NA, Abdul Sattar MZ, Johns EJ, Chik Z, Chung LY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	carboxylated polymers carboxylated polypeptides carrier diabetes renal drug delivery acute kidney injury chronic renal failure end-stage renal failure Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/73cd063f90f44bbba1a4e2a5af98ce70
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spelling	oai:doaj.org-article:73cd063f90f44bbba1a4e2a5af98ce702021-12-02T01:49:51ZRenal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats1178-2013https://doaj.org/article/73cd063f90f44bbba1a4e2a5af98ce702017-01-01T00:00:00Zhttps://www.dovepress.com/renal-targeting-potential-of-a-polymeric-drug-carrier-poly-l-glutamic--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hann-Juang Chai,1 Lik-Voon Kiew,1 Yunni Chin,1 Anwar Norazit,2 Suzita Mohd Noor,2 Yoke-Lin Lo,3,4 Chung-Yeng Looi,1 Yeh-Siang Lau,1 Tuck-Meng Lim,5 Won-Fen Wong,6 Nor Azizan Abdullah,1 Munavvar Zubaid Abdul Sattar,7 Edward J Johns,8 Zamri Chik,1 Lip-Yong Chung3 1Department of Pharmacology, 2Department of Biomedical Science, 3Department of Pharmacy, Faculty of Medicine, University of Malaya, 4School of Pharmacy, International Medical University, Kuala Lumpur, 5Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, 6Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 7School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Malaysia; 8Department of Physiology, University College Cork, Cork, Republic of Ireland 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. Keywords: carboxylated polymers, carboxylated polypeptides, carrier, diabetes, renal drug delivery, acute kidney injury, chronic renal failure, end-stage renal failureChai HJKiew LVChin YNorazit AMohd Noor SLo YLLooi CYLau YSLim TMWong WFAbdullah NAAbdul Sattar MZJohns EJChik ZChung LYDove Medical Pressarticlecarboxylated polymerscarboxylated polypeptidescarrierdiabetesrenal drug deliveryacute kidney injurychronic renal failureend-stage renal failureMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 577-591 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	carboxylated polymers carboxylated polypeptides carrier diabetes renal drug delivery acute kidney injury chronic renal failure end-stage renal failure Medicine (General) R5-920
spellingShingle	carboxylated polymers carboxylated polypeptides carrier diabetes renal drug delivery acute kidney injury chronic renal failure end-stage renal failure Medicine (General) R5-920 Chai HJ Kiew LV Chin Y Norazit A Mohd Noor S Lo YL Looi CY Lau YS Lim TM Wong WF Abdullah NA Abdul Sattar MZ Johns EJ Chik Z Chung LY Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats
description	Hann-Juang Chai,1 Lik-Voon Kiew,1 Yunni Chin,1 Anwar Norazit,2 Suzita Mohd Noor,2 Yoke-Lin Lo,3,4 Chung-Yeng Looi,1 Yeh-Siang Lau,1 Tuck-Meng Lim,5 Won-Fen Wong,6 Nor Azizan Abdullah,1 Munavvar Zubaid Abdul Sattar,7 Edward J Johns,8 Zamri Chik,1 Lip-Yong Chung3 1Department of Pharmacology, 2Department of Biomedical Science, 3Department of Pharmacy, Faculty of Medicine, University of Malaya, 4School of Pharmacy, International Medical University, Kuala Lumpur, 5Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, 6Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 7School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Malaysia; 8Department of Physiology, University College Cork, Cork, Republic of Ireland 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. Keywords: carboxylated polymers, carboxylated polypeptides, carrier, diabetes, renal drug delivery, acute kidney injury, chronic renal failure, end-stage renal failure
format	article
author	Chai HJ Kiew LV Chin Y Norazit A Mohd Noor S Lo YL Looi CY Lau YS Lim TM Wong WF Abdullah NA Abdul Sattar MZ Johns EJ Chik Z Chung LY
author_facet	Chai HJ Kiew LV Chin Y Norazit A Mohd Noor S Lo YL Looi CY Lau YS Lim TM Wong WF Abdullah NA Abdul Sattar MZ Johns EJ Chik Z Chung LY
author_sort	Chai HJ
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	https://doaj.org/article/73cd063f90f44bbba1a4e2a5af98ce70
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Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

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