A novel praziquantel solid lipid nanoparticle formulation shows enhanced bioavailability and antischistosomal efficacy against murine S. mansoni infection

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Radwan A.; El-Lakkany N.M.; William S.; El-Feky G.S.; Al-Shorbagy M.Y.; Saleh S.; Botros S.

Journal: Parasites and Vectors

Publisher: BioMed Central Ltd.

Publication Date: 17 June 2019

Volume / Issue: Volume 12 / Issue 1

Article No.: 304

ISSN: 17563305

DOI: 10.1186/s13071-019-3563-z

Scopus: View on Scopus

PubMed: 31208446

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Radwan A., Research Department, Academy of Scientific Research and Technology, Cairo, Egypt; El-Lakkany N.M., Pharmacology Department, Theodor Bilharz Research Institute, Imbaba, Giza, Egypt; William S., Parasitology Department, Theodor Bilharz Research Institute, Imbaba, Giza, Egypt; El-Feky G.S., Pharmaceutical Technology Department, National Research Center, Giza, Egypt; Al-Shorbagy M.Y., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza, Egypt, School of Pharmacy, Newgiza University, Giza, Egypt; Saleh S., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza, Egypt; Botros S., Pharmacology Department, Theodor Bilharz Research Institute, Imbaba, Giza, Egypt

Abstract

Background: Schistosomiasis is responsible for a considerable global disease burden. This work aimed to improve the therapeutic outcome of the only available antischistosomal drug worldwide, praziquantel (PZQ), by incorporating it into a novel carrier, "solid lipid nanoparticles (SLNs)", to enhance its solubility, bioavailability and efficacy. A simple, cost-effective method was used to prepare SLN-PZQ. Results: Compared to market PZQ (M-PZQ), SLN-PZQ was more bioavailable, as denoted by higher serum concentrations in both normal and infected mice where elevated Ka, AUC0-24, Cmax, and t1/2e with a decrease in kel were demonstrated. The AUC0-24 for SLN-PZQ in normal and Schistosoma mansoni-infected groups was almost nine- and eight-fold higher, respectively, than that for M-PZQ in corresponding groups. In normal and S. mansoni-infected mice, SLN-PZQ was detectable in serum at 24 h, while M-PZQ completely vanished 8 h post-treatment. Additionally, enhanced absorption with extended residence time was recorded for SLN-PZQ. Compared to M-PZQ, SLN-PZQ revealed superior antischistosomal activity coupled with enhanced bioavailability in all treated groups where higher percentages of worm reduction were recorded with all dosages tested. This effect was especially evident at the lower dose levels. The ED95 of SLN-PZQ was 5.29-fold lower than that of M-PZQ, with a significantly higher reduction in both the hepatic and intestinal tissue egg loads of all treated groups and almost complete disappearance of immature deposited eggs (clearly evident at the low dose levels). Conclusions: SLN-PZQ demonstrated enhanced PZQ bioavailability and antischistosomal efficacy with a safe profile despite the prolonged residence in the systemic circulation. © 2019 The Author(s).

Keywords

Bioavailability; Efficacy; Mice; Praziquantel; Schistosoma mansoni; Solid lipid nanoparticles; Animals; Biological Availability; Drug Carriers; Lipids; Male; Nanoparticles; Schistosomiasis mansoni; Schistosomicides; solid lipid nanoparticle; antischistosomal agent; drug carrier; lipid; nanoparticle; animal experiment; animal model; antischistosomal activity; area under the curve; Article; controlled study; cost effectiveness analysis; dispersity; dose response; drug absorption; drug activity; drug bioavailability; drug blood level; drug efficacy; drug formulation; drug release; ED95; intestine; liver; maximum concentration; mouse; nonhuman; particle size; single drug dose; zeta potential; animal; chemistry; drug effect

Citation Information

Scopus Citations: 45

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