Praziquantel in a clay nanoformulation shows more bioavailability and higher efficacy against murine Schistosoma mansoni infection

Theodor Bilharz Research Institute

Bibliographic Information

Authors: El-Feky G.S.; Mohamed W.S.; Nasr H.E.; El-Lakkany N.M.; Seifel-Din S.H.; Botros S.S.

Journal: Antimicrobial Agents and Chemotherapy

Publisher: American Society for Microbiology

Publication Date: June 2015

Volume / Issue: Volume 59 / Issue 6

Pages: 3501–3508

ISSN: 664804

DOI: 10.1128/AAC.04875-14

Scopus: View on Scopus

PubMed: 25845870

Document Type: Article

Access: All Open Access; Green Open Access

Authors and Affiliations

El-Feky G.S., Department of Pharmaceutics, Faculty of Pharmacy, October University for Modern Sciences and Arts, Cairo, Egypt, Department of Pharmaceutical Technology, National Research Center, Cairo, Egypt; Mohamed W.S., Department of Polymers and Pigments, National Research Center, Cairo, Egypt; Nasr H.E., Department of Polymers and Pigments, National Research Center, Cairo, Egypt; El-Lakkany N.M., Department of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt; Seifel-Din S.H., Department of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt; Botros S.S., Department of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt

Abstract

Consideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and its in vivo efficacy against Schistosoma mansoni were investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC0-8) and maximum concentration of drug in serum (Cmax), with a decrease in elimination rate constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Keywords

Animals; Anthelmintics; Biological Availability; Male; Mice; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; cremophor; montmorillonite; anthelmintic agent; animal experiment; animal model; animal tissue; Article; clay; controlled release formulation; controlled study; drug absorption; drug bioavailability; drug efficacy; drug elimination; in vivo study; mouse; nonhuman; particle size; plasma concentration-time curve; priority journal; animal; bioavailability; drug effects; metabolism; pathogenicity

Citation Information

Scopus Citations: 21

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