Overcoming clofazimine intrinsic toxicity: statistical modelling and characterization of solid lipid nanoparticles

Abstract

The aim of this work was to develop solid lipid nanoparticles (SLNs) loaded with clofazimine (CLZ) (SLNs-CLZ) to overcome its intrinsic toxicity and low water solubility, for oral drug delivery. A Box-Behnken design was constructed to unravel the relations between the independent variables in the selected responses. The optimized SLNs-CLZ exhibited the following properties: particle size 230 nm, zeta potential of -34.28 mV, association efficiency of 72% and drug loading of 2.4%, which are suitable for oral delivery. Further characterization included Fourier transformed infrared spectroscopy that confirmed the presence of the drug and the absence of chemical interactions. By differential scanning calorimetry was verified the amorphous state of CLZ. The storage stability studies ensured the stability of the systems over a period of 12 weeks at 4°C. cytotoxicity studies evidenced no effect of both drug-loaded and unloaded SLNs on MKN-28 gastric cells and on intestinal cells, namely Caco-2 and HT29-MTX cells up to 25 µg ml in CLZ. Free CLZ solutions exhibited IC values of 16 and 20 µg ml for Caco-2 and HT29-MTX cells, respectively. It can be concluded that the optimized system, designed considering important variables for the formulation of poorly soluble drugs, represents a promising platform for oral CLZ delivery.

Optimization of Rifapentine-Loaded Lipid Nanoparticles Using a Quality-by-Design Strategy

“…The 3-level, 3-factor design evaluates three independent factors with a fewer number of experiments based on a collection of mathematical and statistical techniques, which leads to reagent savings and to less time-consuming laboratory work [24,25]. In the last decades, the Box-Behnken design has been applied to optimize the process of several drug-loaded nanoparticle formulations [13][14][15][16][17][18].…”

“…Nanoparticles, namely lipid nanoparticles, are considered biodegradable, safe, and constitute a promising strategy for easier and shorter treatment regimens. In the last recent years, quality-by-design studies using response surface methodologies have been used to optimize several drug-loaded nanoformulations [13][14][15][16][17][18]. Accordingly, the present work proposes the optimization and development of nanostructured lipid carriers (NLCs) loaded with RPT as a new delivery system for TB treatment.…”

An investigation on parameters affecting the optimization of testosterone enanthate loaded solid nanoparticles for enhanced transdermal delivery

“…However, the average of the results from 3 different experiments was achieved, and the t-test and Spearman's correlation coefficient were used to do statistical analyses. Finally, a p-value of <0.05 was regarded as statistically significant [32]. (with a weigh of 120-150g) was shaved.…”

Drug Delivery Systems on Leprosy Therapy: Moving Towards Eradication?

“…Polymeric solid dispersions obtained with polyvinylpyrrolidone and DAP using the lyophilization technique, evidenced the presence of the drug in its amorphous state with consequent solubility increase [ 53 ]. Cyclodextrins are cyclic oligosaccharides with a hydrophilic exterior and hydrophobic interior [ 83 ]. This structural feature allows the application of cyclodextrin as solubilizing agents causing hydrophobic drugs to be encapsulated through the formation of a drug-cyclodextrin inclusion complex [ 83 ].…”

“…Cyclodextrins are cyclic oligosaccharides with a hydrophilic exterior and hydrophobic interior [ 83 ]. This structural feature allows the application of cyclodextrin as solubilizing agents causing hydrophobic drugs to be encapsulated through the formation of a drug-cyclodextrin inclusion complex [ 83 ]. Grebogi and co-workers investigated the interactions between DAP and hydroxypropyl-b-cyclodextrin (HPβCD) and β-cyclodextrins (βCD) in the presence and absence of soluble polymers, aiming to increase drug solubility and consequent bioavailability.…”