title: Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm.
abstract: Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ) against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN) suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4°C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% ± 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 ± 11.15 nm, 0.34 ± 0.06, and -11.57 ± 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4°C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91.55%, 87.5%, and 66.7%. When the dose reduced to 0.5 mg/kg, the native drug showed no effect, but the suspension still got the same therapeutic efficacy as that of the 5 mg/kg native PZQ. These results demonstrate that the PZQ-HCO-SLN suspension is a promising formulation to enhance the therapeutic efficacy of PZQ.
authors.affiliation: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Xie
authors.forename: Baoliang
authors.initials: B
authors.lastname: Pan
authors.forename: Baoxin
authors.initials: B
authors.lastname: Shi
authors.forename: Zhuangzhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000923:Anticestodal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D002368:Castor Oil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry*; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000469:parasitology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004443:Echinococcosis / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D048209:Echinococcus granulosus / Q000187:drug effects; D005243:Feces / Q000469:parasitology; D007279:Injections, Subcutaneous; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011223:Praziquantel / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011897:Random Allocation; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000923:Anticestodal Agents; D013535:Suspensions; D011223:Praziquantel; D002368:Castor Oil
references.citation: Clin Microbiol Rev. 2003 Jan;16(1):18-36
references.pmid: 12525423
references.citation: Vet Parasitol. 1994 Aug;54(1-3):295-6
references.pmid: 7846861
references.citation: Parasitol Int. 2006;55 Suppl:S187-91
references.pmid: 16352465
references.citation: Am J Vet Res. 1978 Nov;39(11):1861-2
references.pmid: 736346
references.citation: Nanomedicine (Lond). 2010 Jul;5(5):693-701
references.pmid: 20662641
references.citation: Pharmazie. 2009 Feb;64(2):86-9
references.pmid: 19320279
references.citation: Parasitol Res. 1998;84(3):230-8
references.pmid: 9521013
references.citation: Int J Pharm. 2010 Mar 15;387(1-2):129-38
references.pmid: 20005928
references.citation: Curr Treat Options Neurol. 2000 Jul;2(4):355-360
references.pmid: 11096760
references.citation: Eur J Pharm Biopharm. 2000 Jul;50(1):161-77
references.pmid: 10840199
references.citation: Lancet Infect Dis. 2007 Jun;7(6):385-94
references.pmid: 17521591
references.citation: Parasitol Int. 2006;55 Suppl:S203-6
references.pmid: 16352462
references.citation: Vet Parasitol. 2007 Mar 31;144(3-4):366-70
references.pmid: 17101225
references.citation: Parasitol Res. 2003 Jun;90 Supp 1:S3-9
references.pmid: 12811543
references.citation: Am J Vet Res. 1979 May;40(5):700-1
references.pmid: 475115
references.citation: Bull World Health Organ. 1986;64(3):333-9
references.pmid: 3490317
references.citation: Parasitol Res. 2007 Jan;100(2):317-20
references.pmid: 16915389
references.citation: Ann Trop Med Parasitol. 1997 Mar;91(2):179-86
references.pmid: 9307660
references.citation: Drug Deliv. 2011 Aug;18(6):441-50
references.pmid: 21554156
references.citation: Adv Drug Deliv Rev. 2002 Nov 1;54 Suppl 1:S131-55
references.pmid: 12460720
references.citation: Vet Parasitol. 2010 Nov 24;174(1-2):2-11
references.pmid: 20888694
references.citation: Eur J Clin Pharmacol. 1978 Dec 1;14(4):281-91
references.pmid: 729622
references.citation: Parasitol Int. 2005 Dec;54(4):231-6
references.pmid: 16231860
references.citation: Paediatr Drugs. 2001;3(2):123-35
references.pmid: 11269639
references.citation: Curr Opin Chem Biol. 2007 Aug;11(4):433-9
references.pmid: 17652008
references.citation: Z Parasitenkd. 1977 Jul 21;52(2):117-27
references.pmid: 906623
references.citation: Int J Pharm. 2005 May 13;295(1-2):157-62
references.pmid: 15848000
references.citation: Vet Parasitol. 2010 May 28;170(1-2):158-61
references.pmid: 20197213
references.citation: Parasitol Res. 2001 Jun;87(6):510-2
references.pmid: 11411955
references.citation: Adv Parasitol. 2006;61:443-508
references.pmid: 16735171
references.citation: Vet Ther. 2005 Spring;6(1):15-28
references.pmid: 15906267
references.citation: Clin Microbiol Rev. 2004 Jan;17(1):107-35
references.pmid: 14726458
references.citation: Res Vet Sci. 1977 Jul;23(1):121-3
references.pmid: 905644
references.citation: Ecohealth. 2008 Jun;5(2):115-26
references.pmid: 18787915
references.citation: Trop Med Int Health. 1998 Jun;3(6):462-6
references.pmid: 9657508