A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers

Tetracaine (TTC) is a local anesthetic broadly used for topical and spinal blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid carriers (NLC) may prolong TTC delivery at the site of injection, reducing such toxicity. This work reports the development of NLC loading 4% TTC. Structural properties and encapsulation efficiency (%EE > 63%) guided the selection of three pre-formulations of different lipid composition, through a 23 factorial design of experiments (DOE). DLS and TEM analyses revealed average sizes (193–220 nm), polydispersity (< 0.2), zeta potential |− 21.8 to − 30.1 mV| and spherical shape of the nanoparticles, while FTIR-ATR, NTA, DSC, XRD and SANS provided details on their structure and physicochemical stability over time. Interestingly, one optimized pre-formulation (CP-TRANS/TTC) showed phase-separation after 4 months, as predicted by Raman imaging that detected lack of miscibility between its solid (cetyl palmitate) and liquid (Transcutol) lipids. SANS analyses identified lamellar arrangements inside such nanoparticles, the thickness of the lamellae been decreased by TTC. As a result of this combined approach (DOE and biophysical techniques) two optimized pre-formulations were rationally selected, both with great potential as drug delivery systems, extending the release of the anesthetic (> 48 h) and reducing TTC cytotoxicity against Balb/c 3T3 cells.

Croton argyrophyllus Kunth Essential Oil-Loaded Solid Lipid Nanoparticles: Evaluation of Release Profile, Antioxidant Activity and Cytotoxicity in a Neuroblastoma Cell Line

The essential oil from Croton argyrophyllus Kunth is known for its antiproliferative, anti-inflammatory, antinociceptive, and anticancer activities, and is recognized as a source of phytochemicals for potential use in pharmaceutic and food sectors. Solid lipid nanoparticles (SLN) have been produced to load Croton argyrophyllus (CA) Kunth essential oil (CAEO) and its antioxidant properties evaluated in vitro as a new approach for the treatment of neurodegenerative diseases. Cetyl palmitate SLN loading CAEO (CAEO-SLN) with a mean particle size of 201.4 ± 2.3 nm (polydispersity index 0.211) have been produced by hot high-pressure homogenisation. The release of the oil followed the Korsmeyers-Peppas model. The risk of lipid peroxidation has been determined by applying the production of thiobarbituric acid-reactive substances (TBARS) standard assay. The antioxidant activity was determined by the capacity of the antioxidants existing in CAEO to scavenge the stable radical DPPH•. The cytotoxicity of CA Kunth essential oil-loaded SLN (CAEO-SLN) was evaluated in a human cell line SH-SY5Y (derived from human neuroblastoma) by determining the reduction of the yellow dye 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). Both free essential oil (fEO) and loaded essential oil (CAEO-SLN) were demonstrated to inhibit the Fenton reaction. CAEO-SLN showed DPPH• radical scavenging capacity. The loading of the oil into cetyl palmitate SLN reduced the risk of cytotoxicity.

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

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.