Praziquantel-Solid Lipid Nanoparticles Produced by Supercritical Carbon Dioxide Extraction: Physicochemical Characterization, Release Profile, and Cytotoxicity.

Andrade Andrade,Sanchez-Lopez Sanchez-Lopez,Souto Souto,Oliveira Oliveira,Nery Nery,Alves Alves,Nunes Nunes,Amaral Amaral,Da Silva Da Silva,Severino Severino,Corrêa Corrêa,Chaud Chaud,Gonsalves Gonsalves

doi:10.3390/molecules24213881

Abstract

Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work was to produce cetyl palmitate SLNs using SCF to be loaded with praziquantel (PZQ) as an insoluble model drug. The mean particle size (nm), polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE) were determined on the freshly prepared samples, which were also subject of Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), drug release profile, and in vitro cytotoxicity analyses. PZQ-SLN exhibited a mean size of ~25 nm, PdI ~ 0.5, zeta potential ~−28 mV, and EE 88.37%. The DSC analysis demonstrated that SCF reduced the crystallinity of cetyl palmitate and favored the loading of PZQ into the lipid matrices. No chemical interaction between the PZQ and cetyl palmitate was revealed by FTIR analysis, while the release or PZQ from SLN followed the Weibull model. PZQ-SLN showed low cytotoxicity against fibroblasts cell lines. This study demonstrates that SCF may be a suitable scale-up procedure for the production of SLN, which have shown to be an appropriate carrier for PZQ.

Highlights

Research in pharmaceutical nanotechnology has focused on the development of modified release nanoparticles for the administration of drugs already used in clinical settings, for which several types of drug delivery systems have been proposed in the literature
We describe the development of a new solid lipid nanoparticles (SLNs) formulation produced by Supercritical fluid (SCF) to load praziquantel (PZQ) for oral administration
Conventional encapsulation techniques use a substantial volume of organic solvents and operate at extremely high or low temperatures, resulting in formulations with high polydispersity and high scale-up limitations

Summary

Introduction

Research in pharmaceutical nanotechnology has focused on the development of modified release nanoparticles for the administration of drugs already used in clinical settings, for which several types of drug delivery systems have been proposed in the literature. These systems might promote the higher concentration of the active substance at the target sites, reducing the toxicity on non-specific tissues. The final material is reported to be a dried powder that facilitates the production of improved liquid or solid drug formulations, while the technique is described as environmentally friendly and with the potential to be scaled-up [13]

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