Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes

Qun-You Tan,1,* Jing-Qing Zhang,2,* Na Wang,3,* Hong Yang,4 Xiaoling Li,5 Hua-Rong Xiong,2 Jian-Yong Wu,2 Chun-Jing Zhao,3 Hong Wang,2 Hua-Feng Yin2 1Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 2Medicine Engineering Re...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tan QY, Zhang JQ, Wang N, Yang H, Li X, Xiong HR, Wu JY, Zhao CJ, Wang H, Yin HF
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3946af655a614f7288caf08bb4632567
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3946af655a614f7288caf08bb4632567
record_format	dspace
spelling	oai:doaj.org-article:3946af655a614f7288caf08bb46325672021-12-02T02:36:37ZImproved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes1176-91141178-2013https://doaj.org/article/3946af655a614f7288caf08bb46325672012-07-01T00:00:00Zhttp://www.dovepress.com/improved-biological-properties-and-hypouricemic-effects-of-uricase-fro-a10479https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Qun-You Tan,1,* Jing-Qing Zhang,2,* Na Wang,3,* Hong Yang,4 Xiaoling Li,5 Hua-Rong Xiong,2 Jian-Yong Wu,2 Chun-Jing Zhao,3 Hong Wang,2 Hua-Feng Yin2 1Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 2Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemical &amp; Molecular Pharmacology, Chongqing Medical University, Chongqing, 3School of Pharmacy, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 4School of Pharmacy, Medical College of Soochow University, Soochow, People&#39;s Republic of China; 5TJ Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA, USA*These authors contributed equally to this workObjective: Previous studies on various enzymosomes (functional lipid vesicles encapsulating an enzyme) have been mostly carried out in vitro and have focused on preserving catalytic activity and improving the stability of the enzyme. Until now, few studies have focused on their in vivo fate. Similarly, although we have previously reported the increased in vitro uricolytic activity (about 2.2 times higher than that of free uricase, or three times higher than that of PEGylated uricase, Puricase&reg;, under physiological pH and temperature) and improved stability of the novel alkaline enzymosomes (functional lipid vesicles encapsulating uricase from Candida utilis: uricase-containing lipid vesicles, UOXLVs), it is still necessary to study the biological properties and hypouricemic effects of UOXLVs in vivo.Methods: The enzyme kinetics, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary safety of UOXLVs were evaluated.Results: The Michaelis constant (Km) value of the UOXLVs was slightly lower than that of the free enzyme. The enzyme release from the UOXLVs lasted over 12 hours and their circulation half-life was about sevenfold longer than that of the free uricase. Meanwhile, the UOXLVs had a 22-fold increase in the area under the curve compared with the free uricase. Furthermore, it took less than 3 hours for the UOXLVs to lower the plasma uric acid concentration from a high to a normal level, compared with 6 hours for the free uricase. In addition, the UOXLVs had much less immunogenicity than free uricase and were well tolerated by all animals throughout the observation period.Conclusion: The UOXLVs markedly improved the biological properties and enhanced the hypouricemic effects of uricase in vivo.Keywords: biological properties, hypouricemic effect, uricase, alkaline enzymosomes, in vivoTan QYZhang JQWang NYang HLi XXiong HRWu JYZhao CJWang HYin HFDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 3929-3938 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Tan QY Zhang JQ Wang N Yang H Li X Xiong HR Wu JY Zhao CJ Wang H Yin HF Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes
description	Qun-You Tan,1,* Jing-Qing Zhang,2,* Na Wang,3,* Hong Yang,4 Xiaoling Li,5 Hua-Rong Xiong,2 Jian-Yong Wu,2 Chun-Jing Zhao,3 Hong Wang,2 Hua-Feng Yin2 1Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 2Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemical &amp; Molecular Pharmacology, Chongqing Medical University, Chongqing, 3School of Pharmacy, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 4School of Pharmacy, Medical College of Soochow University, Soochow, People&#39;s Republic of China; 5TJ Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA, USA*These authors contributed equally to this workObjective: Previous studies on various enzymosomes (functional lipid vesicles encapsulating an enzyme) have been mostly carried out in vitro and have focused on preserving catalytic activity and improving the stability of the enzyme. Until now, few studies have focused on their in vivo fate. Similarly, although we have previously reported the increased in vitro uricolytic activity (about 2.2 times higher than that of free uricase, or three times higher than that of PEGylated uricase, Puricase&reg;, under physiological pH and temperature) and improved stability of the novel alkaline enzymosomes (functional lipid vesicles encapsulating uricase from Candida utilis: uricase-containing lipid vesicles, UOXLVs), it is still necessary to study the biological properties and hypouricemic effects of UOXLVs in vivo.Methods: The enzyme kinetics, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary safety of UOXLVs were evaluated.Results: The Michaelis constant (Km) value of the UOXLVs was slightly lower than that of the free enzyme. The enzyme release from the UOXLVs lasted over 12 hours and their circulation half-life was about sevenfold longer than that of the free uricase. Meanwhile, the UOXLVs had a 22-fold increase in the area under the curve compared with the free uricase. Furthermore, it took less than 3 hours for the UOXLVs to lower the plasma uric acid concentration from a high to a normal level, compared with 6 hours for the free uricase. In addition, the UOXLVs had much less immunogenicity than free uricase and were well tolerated by all animals throughout the observation period.Conclusion: The UOXLVs markedly improved the biological properties and enhanced the hypouricemic effects of uricase in vivo.Keywords: biological properties, hypouricemic effect, uricase, alkaline enzymosomes, in vivo
format	article
author	Tan QY Zhang JQ Wang N Yang H Li X Xiong HR Wu JY Zhao CJ Wang H Yin HF
author_facet	Tan QY Zhang JQ Wang N Yang H Li X Xiong HR Wu JY Zhao CJ Wang H Yin HF
author_sort	Tan QY
title	Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes
title_short	Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes
title_full	Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes
title_fullStr	Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes
title_full_unstemmed	Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes
title_sort	improved biological properties and hypouricemic effects of uricase from candida utilis loaded in novel alkaline enzymosomes
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/3946af655a614f7288caf08bb4632567
work_keys_str_mv	AT tanqy improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT zhangjq improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT wangn improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT yangh improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT lix improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT xionghr improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT wujy improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT zhaocj improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT wangh improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes AT yinhf improvedbiologicalpropertiesandhypouricemiceffectsofuricasefromcandidautilisloadedinnovelalkalineenzymosomes
_version_	1718402342718537728

Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes

Ejemplares similares