Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against <em>Mycobacterium tuberculosis</em>

Abstract

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Cessation of treatment before the recommended conclusion may lead to the emergence of multidrug-resistant strains. The aim of this study was to develop nanostructured lipid carriers (NLCs) for use in the treatment of M. tuberculosis. The NLCs comprised the following lipid phase: 2.07% polyoxyethylene 40 stearate, 2.05% caprylic/capric triglyceride, and 0.88% polyoxyl 40 hydrogenated castor oil; the following aqueous phase: 3.50% poloxamer 407 (F1–F6), and 0.50% cetyltrimethylammonium bromide (F7–F12); and incorporated the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2), and [Cu(NCO)2(INH)2]·4H2O (3) to form compounds F11.1, F11.2, and F11.3, respectively. The mean diameter of F11, F11.1, F11.2, and F11.3 ranged from 111.27±21.86 to 134.25±22.72 nm, 90.27±12.97 to 116.46±9.17 nm, 112.4±10.22 to 149.3±15.82 nm, and 78.65±6.00 to 122.00±8.70 nm, respectively. The polydispersity index values for the NLCs ranged from 0.13±0.01 to 0.30±0.09. The NLCs showed significant changes in zeta potential, except for F11.2, with F11, F11.1, F11.2, and F11.3 ranging from 18.87±4.04 to 23.25±1.13 mV, 17.03±1.77 to 21.42±1.87 mV, 20.51±1.88 to 22.60±3.44 mV, and 17.80±1.96 to 25.25±7.78 mV, respectively. Atomic force microscopy confirmed the formation of nanoscale spherical particle dispersions by the NLCs. Differential scanning calorimetry determined the melting points of the constituents of the NLCs. The in vitro activity of copper(II) complex-loaded NLCs against M. tuberculosis H37Rv showed an improvement in the anti-TB activity of 55.4, 27.1, and 41.1 times the activity for complexes 1, 2, and 3, respectively. An in vivo acute toxicity study of complex-loaded NLCs demonstrated their reduced toxicity. The results suggest that NLCs may be a powerful tool to optimize the activity of copper(II) complexes against M. tuberculosis.

Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations

“…The authors believe that these results may be a consequence of the composition of the microemulsion, since the presence of surfactants and the oil phase may promote a better diffusion of the compound or drug, enhancing its permeation. The same was stated by El-Hadidy et al (2012) and Sato et al (2017) by incorporating the drug voriconazole and the antifungal complexes of the microemulsions and copper nanostructured lipid carriers, respectively, showed that the antimicrobial activity increased significantly. The assays on keratinocyte monolayers proved the ability to reduce toxicity when nonyl was incorporated into the NLS.…”

Nanotechnological strategies for systemic microbial infections treatment: A review

“…Important studies in the scientific literature suggest that nanostructured lipid carriers can increase the dissolution of drugs and decrease toxicity, thus improving bioavailability and, therefore, these systems show to be very promising ( Elmowafy et al, 2018 , Jansook et al, 2019 , Ling et al, 2019 , Nordin et al, 2018 , Souto et al, 2011 , Yang et al, 2014 ). According to these advantages of NLC, in recent decades they have obtained excellent results and several applications, such as oral, topical, parenteral and ocular administration ( Müller et al, 2002 , Sato et al, 2017 ). This system can lead to some disadvantages such as irritative action by sensitivity to some surfactants, application and efficiency in the case of proteins and peptides ( Jaiswal et al, 2016 , Schäfer-Korting et al, 2007 ).…”

Comparative Study of Glyceryl Behenate or Polyoxyethylene 40 Stearate-Based Lipid Carriers for Trans-Resveratrol Delivery: Development, Characterization and Evaluation of the In Vitro Tyrosinase Inhibition

“…NLCs were prepared by the high shear homogenization technique [24]. First, components of the lipid phase (PEG-40 stearate or glyceryl behenate, CCTG, and castor oil) and components of the aqueous phase (poloxamer 407, methylparaben, propylparaben, and Milli-Q water) were heated separately at 70°C.…”