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

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....

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Autores principales: Amara, Rokaya O, Ramadan, Alyaa A, El-Moslemany, Riham M, Eissa, Maha M, El-Azzouni, Mervat Z, El-Khordagui, Labiba K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084080/
https://www.ncbi.nlm.nih.gov/pubmed/30122922
http://dx.doi.org/10.2147/IJN.S167285
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author Amara, Rokaya O
Ramadan, Alyaa A
El-Moslemany, Riham M
Eissa, Maha M
El-Azzouni, Mervat Z
El-Khordagui, Labiba K
author_facet Amara, Rokaya O
Ramadan, Alyaa A
El-Moslemany, Riham M
Eissa, Maha M
El-Azzouni, Mervat Z
El-Khordagui, Labiba K
author_sort Amara, Rokaya O
collection PubMed
description 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 post-absorption 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.
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spelling pubmed-60840802018-08-17 Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting Amara, Rokaya O Ramadan, Alyaa A El-Moslemany, Riham M Eissa, Maha M El-Azzouni, Mervat Z El-Khordagui, Labiba K Int J Nanomedicine Original Research 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 post-absorption 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. Dove Medical Press 2018-08-06 /pmc/articles/PMC6084080/ /pubmed/30122922 http://dx.doi.org/10.2147/IJN.S167285 Text en © 2018 Amara et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Amara, Rokaya O
Ramadan, Alyaa A
El-Moslemany, Riham M
Eissa, Maha M
El-Azzouni, Mervat Z
El-Khordagui, Labiba K
Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential Schistosoma mansoni tegumental targeting
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084080/
https://www.ncbi.nlm.nih.gov/pubmed/30122922
http://dx.doi.org/10.2147/IJN.S167285
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