Diethyldithiocarbamate loaded in beeswax-copaiba oil nanoparticles obtained by solventless double emulsion technique promote promastigote death in vitro

Abstract

Leishmaniasis is considered a neglected tropical disease that represents a Public Health problem due to its high incidence. In the search of new alternatives for Leishmaniasis treatment diethyldithiocarbamate (DETC) has shown an excellent leishmanicidal activity and the incorporation into drug carrier systems, such as solid lipid nanoparticles (SLNs), is very promising. In the present work DETC loaded in beeswax nanoparticles containing copaiba oil were obtained by the double emulsion/melt technique. The nanoparticles were characterized and leishmanicidal activity against L. amazonensis promastigotes forms and cytotoxicity in murine macrophages were evaluated. SLNs presented size below 200 nm, spherical morphology, negative charge surface, high encapsulation efficiency, above 80%, and excellent stability. Moreover, Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses were performed to evaluate the chemical structure and possible interactions between DETC and SLNs. SLNs provided a protection for DETC, decreasing its cytotoxic effects in macrophages, which led to an improvement in the selectivity against the parasites, which almost doubled from free DETC (11.4) to DETC incorporated in SLNs (18.2). These results demonstrated that SLNs had a direct effect on L. amazonensis promastigotes without affect the viability of macrophage cell, can be a promising alternative therapy for the cutaneous treatment of L. amazonensis

Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery and the Effects of Preparation Parameters of Solvent Injection Method

“…Particularly, it has been widely used to incorporate insulin into the matrices of SLNs and NLCs for oral delivery [ 102 , 103 , 104 ]. According to this method, a drug and a stabilizer are dissolved in an aqueous solution and then emulsified in a water-immiscible organic phase containing lipids [ 105 ] or in solvent-free molten lipids [ 106 , 107 ]. These primary emulsions are dispersed in an aqueous phase containing a hydrophilic emulsifier to form water/oil/water (w/o/w) emulsion.…”

“…After w/o/w emulsion was formed, the emulsion was poured into cold water (2–5 °C) to solidify NLCs [ 107 ]. A similar strategy was used to prepare diethyldithiocarbamate-loaded SLNs with PSs of <200 nm and EEs of >80% [ 106 ]. The advantage of the double emulsion method is that it does not require molten lipid.…”

“…EEs of SLNs and NLCs produced using this technique may range from 5.2–40.3% for insulin [ 108 ] or relatively higher (63%) for sulforhodamine 101 [ 107 ]. In some cases, EEs can also reach 80% for diethyldithiocarbamate [ 106 ] and 90% for polymyxin B sulfate [ 109 ]. In addition, the SLNs and NLCs prepared using this method have relatively large PSs (up to micro sizes) [ 55 , 75 ].…”

Nanoparticles/nanoplatform to carry and deliver the drug molecules to the target site

“…The double emulsion can fix the problem of low encapsulation efficiency of hydrophilic drugs in o/w emulsion since hydrophilic molecules are often encapsulated using w/o/w emulsion method. Several studies have reported the interest of using a double emulsionevaporation process in drug delivery [9], [21]. Recently, w/o/w emulsion was produced to encapsulate Memantine, an approved anti-Alzheimer agent, into PLGA nanoparticles.…”

Trypanosomatid-Caused Conditions: State of the Art of Therapeutics and Potential Applications of Lipid-Based Nanocarriers

“…It demonstrated potent in vitro efficacy, and it almost completely suppressed parasite replication in the spleen, whereas it also inhibited the parasite replication in the liver. Mazur et al (2019) devised beeswax nanoparticles containing copaiba oil to encapsulate diethyldithiocarbamate, which has previously shown excellent leishmanicidal effect. The nanoformulation decreased the cytotoxic effects of the drug against macrophages, which led to an almost 2-fold increase in the selectivity index.…”