Nanostructured Lipid Carriers as a Strategy to Improve the &lt;I&gt;In Vitro&lt;/I&gt; Schistosomiasis Activity of Praziquantel

Kolenyak-Santos, Fernanda; Garnero, Claudia; Oliveira, Rosimeire Nunes de; Souza, Ana Luiza Ribeiro de; Chorilli, Marlus; Allegretti, Silmara Marques; Longhi, Marcela R.; Chaud, Marco V.; Gremião, Maria Palmira Daflon

doi:10.1166/jnn.2015.9186

Cited by 34 publications

(20 citation statements)

References 33 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The schistosomal tegument, as a site of vital and immunological functions for the host response and parasite survival[ 12 ],may present a therapeutic target for drugs having antischistosomal activity. This can be supported by the enhanced tegument damage, induced by PZQ nanometric delivery systems via increasing drug concentration and/or activity [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study

et al. 2015

View full text Add to dashboard Cite

Miltefosine (MFS) is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD). This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs) as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%), good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs, allowing targeting via the oral route. From a clinical point of view, data suggest MFS-LNCs as a potential single dose oral nanomedicine for enhanced therapy of schistosomiasis mansoni and possibly other diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study

et al. 2015

View full text Add to dashboard Cite

show abstract

“…[4] Different strategies have been proposed for improvement of PZQ delivery in human bodies, including solid dispersion of PZQ in polyvinylpyrrolidone (PVP) [6,9] and other excipients, such as cyclodextrins [10,11] and solid lipid nanoparticles (SLN). [12,13] Encapsulation of PZQ in polymer nanoparticles and microparticles also constitutes a promising alternative for enhancement of PZQ dissolution rates in body fluids and masking of the inherent bitter taste. [2,8,[14][15][16] Particularly, nanotechnologies have helped the development of more efficient drug delivery systems, expanding the range of pharmaceutical formulation products.…”

mentioning

confidence: 99%

In situ encapsulation of praziquantel through methyl methacrylate/diethylaminoethyl methacrylate and MMA/DMAEMA miniemulsion copolymerizations in presence of distinct ionic surfactants

et al. 2021

View full text Add to dashboard Cite

Schistosomiasis is a neglected tropical disease that affects primarily the poorest and most vulnerable populations. Although praziquantel (PZQ) is the drug used most frequently for treatment of schistosomiasis, PZQ presents unpleasant bitter taste and low solubility in water, which prejudice the implementation of pediatric treatments. For this reason, the main purpose of the present work was the production of stable nanoparticles loaded with PZQ through in situ miniemulsion copolymerizations of methyl methacrylate (MMA) with diethylaminoethyl methacrylate (DEAEMA) or dimethylaminoethyl methacrylate (DMAEMA). Due to the cationic nature of the comonomers, the use of different ionic surfactants was also investigated. Nanoparticles with narrow particle size distributions, characteristic average diameters ranging from 50 nm to 110 nm, and loaded with 20 wt% of PZQ were manufactured successfully PZQ encapsulation efficiencies were higher than 97 wt% and PZQ was homogeneously dispersed in the final polymer matrix. Finally, the use of a cationic surfactant with DEAEMA cationic comonomer led to more stable latexes because of the high absolute value of the zeta potential.

show abstract

“…Several studies revealed an enhanced safety profile for lipid-carrier nanoformulations [23]. Moreover, PZQ showed an enhanced safety profile when incorporated in nanostructured lipid carriers [67], but liposomes and lipid emulsions as drug delivery systems revealed major drawbacks of drug leakage, hydrolysis, possible particle growth and instability during storage [22]. PZQ in nanoclay revealed significantly higher bioavailability and efficacy were recorded; nonetheless, there have been significant changes in haematological analysis and alterations in the cellular electrolyte balance in normal rats following the administration of large doses of montmorillonite clay [68–70].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

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 K a , AUC 0–24 , C max , and t 1/2e with a decrease in k el were demonstrated. The AUC 0–24 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 ED 95 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.

show abstract

Nanostructured Lipid Carriers as a Strategy to Improve the <I>In Vitro</I> Schistosomiasis Activity of Praziquantel

Cited by 34 publications

References 33 publications

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study

In situ encapsulation of praziquantel through methyl methacrylate/diethylaminoethyl methacrylate and MMA/DMAEMA miniemulsion copolymerizations in presence of distinct ionic surfactants

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

Contact Info

Product

Resources

About