Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting

Rokaya O Amara,1,2 Alyaa A Ramadan,1 Riham M El-Moslemany,1 Maha M Eissa,3 Mervat Z El-Azzouni,3 Labiba K El-Khordagui1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Biotechnology Research Center, Tripoli, Libya; 3Department of Medical Parasitology, F...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Amara RO, Ramadan AA, El-Moslemany RM, Eissa MM, El-Azzouni MZ, El-Khordagui LK
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
Lipid nanocapsules
praziquantel
Schistosoma mansoni
bioavailability
oral targeting
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/9bffa63920104174bc8802474cad48bb
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:9bffa63920104174bc8802474cad48bb
record_format dspace
spelling oai:doaj.org-article:9bffa63920104174bc8802474cad48bb2021-12-02T05:17:18ZPraziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting1178-2013https://doaj.org/article/9bffa63920104174bc8802474cad48bb2018-08-01T00:00:00Zhttps://www.dovepress.com/praziquantel-lipid-nanocapsules-an-oral-nanotherapeutic-with-potential-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Rokaya O Amara,1,2 Alyaa A Ramadan,1 Riham M El-Moslemany,1 Maha M Eissa,3 Mervat Z El-Azzouni,3 Labiba K El-Khordagui1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Biotechnology Research Center, Tripoli, Libya; 3Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt Purpose: Lipid nanocapsules (LNCs) have shown potential to increase the bioavailability and efficacy of orally administered drugs. However, their intestinal translocation to distal target sites and their implication in pharmacokinetic (PK)–pharmacodynamic (PD) relationships are yet to be elucidated. In this study, the effect of LNCs on the PD activity and pharmacokinetics of praziquantel (PZQ), the mainstay of schistosomiasis chemotherapy, was investigated. Materials and methods: The composition of LNCs was modified to increase PZQ payload and to enhance membrane permeability. PZQ–LNCs were characterized in vitro for colloidal properties, entrapment efficiency (EE%), and drug release. PD activity of the test formulations was assessed in Schistosoma mansoni-infected mice 7 days post-oral administration of a single 250 mg/kg oral dose. Pharmacokinetics of the test formulations and their stability in simulated gastrointestinal (GI) fluids were investigated to substantiate in vivo data. Results: PZQ–LNCs exhibited good pharmaceutical attributes in terms of size (46–62 nm), polydispersity index (0.01–0.08), EE% (>95%), and sustained release profiles. Results indicated significant efficacy enhancement by reduction in worm burden, amelioration of liver pathology, and extensive damage to the fluke suckers and tegument. This was partly explained by PK data determined in rats. In addition, oral targeting of the worms was supported by the stability of PZQ–LNCs in simulated GI fluids and scanning electron microscopy (SEM) visualization of nanostructures on the tegument of worms recovered from mesenteric/hepatic veins. Cytotoxicity data indicated tolerability of PZQ–LNCs. Conclusion: Data obtained provide evidence for the ability of oral LNCs to target distal postabsorption sites, leading to enhanced drug efficacy. From a practical standpoint, PZQ–LNCs could be suggested as a potential tolerable single lower dose oral nanomedicine for more effective PZQ mass chemotherapy. Keywords: lipid nanocapsules, praziquantel, Schistosoma mansoni, bioavailability, oral targeting, pharmacokinetics, tegumentAmara RORamadan AAEl-Moslemany RMEissa MMEl-Azzouni MZEl-Khordagui LKDove Medical PressarticleLipid nanocapsulespraziquantelSchistosoma mansonibioavailabilityoral targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4493-4505 (2018)
institution DOAJ
collection DOAJ
language EN
topic Lipid nanocapsules
praziquantel
Schistosoma mansoni
bioavailability
oral targeting
Medicine (General)
R5-920
spellingShingle Lipid nanocapsules
praziquantel
Schistosoma mansoni
bioavailability
oral targeting
Medicine (General)
R5-920
Amara RO
Ramadan AA
El-Moslemany RM
Eissa MM
El-Azzouni MZ
El-Khordagui LK
Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting
description Rokaya O Amara,1,2 Alyaa A Ramadan,1 Riham M El-Moslemany,1 Maha M Eissa,3 Mervat Z El-Azzouni,3 Labiba K El-Khordagui1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Biotechnology Research Center, Tripoli, Libya; 3Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt Purpose: Lipid nanocapsules (LNCs) have shown potential to increase the bioavailability and efficacy of orally administered drugs. However, their intestinal translocation to distal target sites and their implication in pharmacokinetic (PK)–pharmacodynamic (PD) relationships are yet to be elucidated. In this study, the effect of LNCs on the PD activity and pharmacokinetics of praziquantel (PZQ), the mainstay of schistosomiasis chemotherapy, was investigated. Materials and methods: The composition of LNCs was modified to increase PZQ payload and to enhance membrane permeability. PZQ–LNCs were characterized in vitro for colloidal properties, entrapment efficiency (EE%), and drug release. PD activity of the test formulations was assessed in Schistosoma mansoni-infected mice 7 days post-oral administration of a single 250 mg/kg oral dose. Pharmacokinetics of the test formulations and their stability in simulated gastrointestinal (GI) fluids were investigated to substantiate in vivo data. Results: PZQ–LNCs exhibited good pharmaceutical attributes in terms of size (46–62 nm), polydispersity index (0.01–0.08), EE% (>95%), and sustained release profiles. Results indicated significant efficacy enhancement by reduction in worm burden, amelioration of liver pathology, and extensive damage to the fluke suckers and tegument. This was partly explained by PK data determined in rats. In addition, oral targeting of the worms was supported by the stability of PZQ–LNCs in simulated GI fluids and scanning electron microscopy (SEM) visualization of nanostructures on the tegument of worms recovered from mesenteric/hepatic veins. Cytotoxicity data indicated tolerability of PZQ–LNCs. Conclusion: Data obtained provide evidence for the ability of oral LNCs to target distal postabsorption sites, leading to enhanced drug efficacy. From a practical standpoint, PZQ–LNCs could be suggested as a potential tolerable single lower dose oral nanomedicine for more effective PZQ mass chemotherapy. Keywords: lipid nanocapsules, praziquantel, Schistosoma mansoni, bioavailability, oral targeting, pharmacokinetics, tegument
format article
author Amara RO
Ramadan AA
El-Moslemany RM
Eissa MM
El-Azzouni MZ
El-Khordagui LK
author_facet Amara RO
Ramadan AA
El-Moslemany RM
Eissa MM
El-Azzouni MZ
El-Khordagui LK
author_sort Amara RO
title Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting
title_short Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting
title_full Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting
title_fullStr Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting
title_full_unstemmed Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting
title_sort praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential schistosoma mansoni tegumental targeting
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/9bffa63920104174bc8802474cad48bb
work_keys_str_mv AT amararo praziquantelndashlipidnanocapsulesanoralnanotherapeuticwithpotentialschistosomamansonitegumentaltargeting
AT ramadanaa praziquantelndashlipidnanocapsulesanoralnanotherapeuticwithpotentialschistosomamansonitegumentaltargeting
AT elmoslemanyrm praziquantelndashlipidnanocapsulesanoralnanotherapeuticwithpotentialschistosomamansonitegumentaltargeting
AT eissamm praziquantelndashlipidnanocapsulesanoralnanotherapeuticwithpotentialschistosomamansonitegumentaltargeting
AT elazzounimz praziquantelndashlipidnanocapsulesanoralnanotherapeuticwithpotentialschistosomamansonitegumentaltargeting
AT elkhordaguilk praziquantelndashlipidnanocapsulesanoralnanotherapeuticwithpotentialschistosomamansonitegumentaltargeting
_version_ 1718400486172786688

Ejemplares similares