title: Uricase alkaline enzymosomes with enhanced stabilities and anti-hyperuricemia effects induced by favorable microenvironmental changes.
abstract: Enzyme therapy is an effective strategy to treat diseases. Three strategies were pursued to provide the favorable microenvironments for uricase (UCU) to eventually improve its features: using the right type of buffer to constitute the liquid media where catalyze reactions take place; entrapping UCU inside the selectively permeable lipid vesicle membranes; and entrapping catalase together with UCU inside the membranes. The nanosized alkaline enzymosomes containing UCU/(UCU and catalase) (ESU/ESUC) in bicine buffer had better thermal, hypothermal, acid-base and proteolytic stabilities, in vitro and in vivo kinetic characteristics, and uric acid lowering effects. The favorable microenvironments were conducive to the establishment of the enzymosomes with superior properties. It was the first time that two therapeutic enzymes were simultaneously entrapped into one enzymosome having the right type of buffer to achieve added treatment efficacy. The development of ESU/ESUC in bicine buffer provides valuable tactics in hypouricemic therapy and enzymosomal application.
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Wu
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Biyue
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000468:Alkalies / Q000737:chemistry; D002374:Catalase / Q000008:administration & dosage / Q000737:chemistry; D060833:Cellular Microenvironment / Q000187:drug effects; D016503:Drug Delivery Systems; D057487:Enzyme Therapy; D006801:Humans; D033461:Hyperuricemia / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014503:Urate Oxidase / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000468:Alkalies; D008055:Lipids; D008081:Liposomes; D011092:Polyethylene Glycols; D002374:Catalase; D014503:Urate Oxidase
references.citation: J Natl Cancer Inst. 2007 Dec 5;99(23):1768-81
references.pmid: 18042934
references.citation: Molecules. 2013;18(11):14349-65
references.pmid: 24264137
references.citation: Drug Deliv. 2010 Jan;17(1):28-37
references.pmid: 22747073
references.citation: Biol Blood Marrow Transplant. 2014 May;20(5):730-4
references.pmid: 24530972
references.citation: Int J Pharm. 2010 Jan 15;384(1-2):165-72
references.pmid: 19782743
references.citation: Pharm Res. 2015 Jan;32(1):91-102
references.pmid: 25037861
references.citation: Arch Pharm Res. 2014 Oct;37(10):1336-44
references.pmid: 24866061
references.citation: Med Hypotheses. 2010 Feb;74(2):396-7
references.pmid: 19762160
references.citation: Farmaco. 2000 Apr;55(4):264-9
references.pmid: 10966157
references.citation: J Pharm Pharmacol. 2013 Jan;65(1):53-63
references.pmid: 23215688
references.citation: Am J Kidney Dis. 2013 Sep;62(3):481-92
references.pmid: 23684124
references.citation: J Inherit Metab Dis. 2015 Mar;38(2):305-14
references.pmid: 24715333
references.citation: Curr Drug Saf. 2011 Nov 1;6(5):329-38
references.pmid: 22424541
references.citation: Biochemistry. 2013 Jan 22;52(3):497-507
references.pmid: 23237426
references.citation: J Ethnopharmacol. 2012 Jun 26;142(1):248-52
references.pmid: 22575704
references.citation: Appl Microbiol Biotechnol. 2011 Nov;92(3):529-37
references.pmid: 21573940
references.citation: Bioresour Technol. 2015 May;184:429-35
references.pmid: 25306444
references.citation: FEBS Lett. 2014 May 2;588(9):1715-9
references.pmid: 24657440
references.citation: Eur J Pharm Biopharm. 2012 Sep;82(1):43-8
references.pmid: 22705639
references.citation: Acta Crystallogr F Struct Biol Commun. 2014 Jul;70(Pt 7):896-902
references.pmid: 25005084
references.citation: Int J Nanomedicine. 2012;7:3929-38
references.pmid: 22915844
references.citation: Methods Mol Biol. 2011;679:9-18
references.pmid: 20865384
references.citation: Cochrane Database Syst Rev. 2014;8:CD006945
references.pmid: 25121561
references.citation: Neurology. 2013 Mar 19;80(12):1173
references.pmid: 23509050
references.citation: Chem Cent J. 2013 Apr 17;7(1):69
references.pmid: 23594729
references.citation: Future Med Chem. 2011 Jan;3(1):9-13
references.pmid: 21428822
references.citation: Semin Arthritis Rheum. 2014 Aug;44(1):25-30
references.pmid: 24560169
references.citation: Neural Regen Res. 2014 Mar 1;9(5):458-9
references.pmid: 25206837
references.citation: ACS Appl Mater Interfaces. 2015 Sep 16;7(36):20255-63
references.pmid: 26325262
references.citation: Appl Biochem Biotechnol. 2014 Jan;172(2):1055-69
references.pmid: 24142354
references.citation: J Oral Maxillofac Surg. 2013 Jul;71(7):1261-7
references.pmid: 23566694
references.citation: Beilstein J Org Chem. 2010 Apr 01;6:31
references.pmid: 20502603
references.citation: Intern Med J. 2012 Sep;42(9):997-1007
references.pmid: 24020339
references.citation: Evid Based Complement Alternat Med. 2014;2014:873607
references.pmid: 24883071
references.citation: Am J Kidney Dis. 2014 Oct;64(4):550-7
references.pmid: 24906981
references.citation: Drugs Today (Barc). 2012 Jul;48(7):441-9
references.pmid: 22844655
references.citation: Curr Opin Rheumatol. 2014 Mar;26(2):169-75
references.pmid: 24445479
references.citation: Appl Biochem Biotechnol. 2013 Jun;170(4):868-79
references.pmid: 23615735
references.citation: Ann Chim. 2005 Jan-Feb;95(1-2):105-9
references.pmid: 15801182
references.citation: J Control Release. 2013 Oct 10;171(1):57-62
references.pmid: 23838153
references.citation: Comput Biol Med. 2012 Jun;42(6):657-66
references.pmid: 22537975
references.citation: ACS Nano. 2014 May 27;8(5):4996-5009
references.pmid: 24720540
references.citation: PLoS One. 2014;9(1):e86651
references.pmid: 24466188
references.citation: Biotechnol Appl Biochem. 2015 Jan-Feb;62(1):137-44
references.pmid: 24673428
references.citation: Artif Cells Nanomed Biotechnol. 2013 Oct;41(5):327-31
references.pmid: 23305069
references.citation: Molecules. 2012;17(4):3945-56
references.pmid: 22466854
references.citation: Appl Biochem Biotechnol. 2013 May;170(1):32-43
references.pmid: 23463327