Intestinal Lymphatic Delivery of Praziquantel by Solid Lipid Nanoparticles: Formulation Design,In VitroandIn VivoStudies

Abstract

The aim of the present work was to design and develop Praziquantal (PZQ) loaded solid lipid nanoparticles (PZQ-SLN) to improve the oral bioavailability by targeting intestinal lymphatic system. PZQ is practically insoluble in water and exhibits extensive hepatic first-pass metabolism. PZQ SLN were composed of triglycerides, lecithin and various aqueous surfactants; were optimized using hot homogenization followed by ultrasonication method. The optimized SLN had particle size of123±3.41 nm, EE of86.6±5.72%. The drug release of PZQ-SLN showed initial burst release followed by the sustained release. Inspite of zeta potential being around −10 mV, the optimized SLN were stable at storage conditions (5±3°C and25±2°C/60±5% RH) for six months. TEM study confirmed the almost spherical shape similar to the control formulations. Solid state characterization using differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) analysis confirmed the homogeneous distribution of PZQ within the lipid matrix. The 5.81-fold increase inAUC0→∞, after intraduodenal administration of PZQ-SLN in rats treated with saline in comparison to rats treated with cycloheximide (a blocker of intestinal lymphatic pathway), confirmed its intestinal lymphatic delivery. The experimental results indicate that SLN may offer a promising strategy for improving the therapeutic efficacy and reducing the dose.

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

“…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 ].…”

Enhanced and Extended Anti-Hypertensive Effect of VP5 Nanoparticles

“…The short W1/O sonication time was suggested to cause VP5 incompletely being entrapped in the primary emulsion and lower down the EE%. Longer sonication time was speculated to break the coarse emulsion drops into nanodroplets, which could cause the observed particle size of VP5-NPs and the improved EE% [34]. However, when the formation of primary emulsion was good, longer sonication time would lead to the leakage of VP5 from the internal phase to the external phase, causing a decrease in EE%.…”

Nanomedicine Approaches Against Parasitic Worm Infections

“…One alternative strategy to improve bioavailability of PZQ is loading the drug in solid lipid nanoparticles (SLNs) . In one example, PZQ was entrapped in SLNs through ultrasonication that produced nanoparticles with sizes of ≈100 nm .…”

“…Oral administration of PZQ‐loaded SLNs in rats was found to improve bioavailability compared to the free drug: the total amount of drug absorbed by the body was estimated to be ≈4 times higher, and the mean‐residence‐time also showed a twofold increase . Interestingly, PZQ loaded in SLNs appeared to reach the systemic circulation through the intestinal lymphatic system . When the nanoparticles were administered intraduodenally to rats that are pretreated with cycloheximide (a reagent commonly used to block the transport through intestinal lymphatic pathway), the peak plasma concentration of PZQ was reduced by over 60%, and the total amount of drug absorbed by the body was over five times lower …”