Fucoidan coated liposomes loaded with novel antituberculosis agent: preparation, evaluation, and cytotoxicity study.

In this article, we described a novel antituberculosis imidazotetrazine derivative designed in fucoidan-coated liposomes to reduce its cytotoxicity and investigate its mucoadhesive properties. Firstly, fucoidan extracted from Ascophyllum nodosum was used for additional stabilization of liposomal suspensions and to give it mucoadhesive properties. PEG-600 and/or Tween-80 were used to increase the shelf life of liposomal suspension. The ratio of the fucoidan: lipids 1:2 was found to be the optimum that produces stable fucoidan-coated liposomes. The particle size of the optimum formulation was 336.3 ± 5.4, the PDI was 0.33, and the zeta potential was -39.6. This size and the practical spherical shape of the particles were confirmed by atomic force microscopy. In addition, the in vitro release profiles from uncoated and fucoidan-coated liposomes revealed significant and faster release compared to free antituberculosis agent. Using the MTT assay test, the fucoidan-coated liposomes exhibited fourteen times lower cytotoxicity (IC50 7.14 ± 0.91 µg/ml) than the free drug (IC50 0.49 ± 0.06). Moreover, the mucoadhesive capabilities of these liposomal formulations were also confirmed using snail mucin, which highlighting their potential use as an effective delivery system for antituberculosis therapy, with notable improvements in dissolution rate and reduced cytotoxicity.

Effective pickering emulsifiers based on submicron carboxymethyl cellulose/chitosan polymer particles.

In this study, cross-linked carboxymethyl cellulose/chitosan submicron particles were employed to facilitate the stabilization of Pickering emulsion. The polymer particles were prepared using the polyelectrolyte self-assembly method in conjunction with isocyanide based multicomponent reactions and the characteristics were obtained using: nuclear magnetic resonance, Fourier-transform infrared spectroscopy and dynamic light scattering. Atomic force microscopy revealed the heterogeneous structure of the resulting submicron particles with domains of 20-30 nm in size. The average diameter was found to be in the range of 229-378 nm and they were found to be suitable for the fabrication of oil/water Pickering emulsion when proceeded via the homogenization method followed by sonication. The results obtained revealed that carboxymethyl cellulose/chitosan particles significantly stabilized the droplets at the oil/water interface. Even at low particle concentrations of 0.3 g/L (which is close to that of low molecular weight surfactants) stable Pickering emulsions have been obtained. Additionally, the resulting emulsions showed a high level of stability with regard to changes in pH, temperature and ionic strength. The natural alkaloid piperine was used as a model compound to load the resulting particles, which possessed encapsulation efficiency of 90.6±0.4%. Furthermore, the in vitro release profile of piperine from the Pickering emulsion revealed a much-controlled release in both acidic and neutral media as compared to the unformulated piperine. Additional findings in this work revealed important information on the application of carboxymethyl cellulose/chitosan submicron particles as Pickering stabilizers for creation of new delivery systems.

Optimization, characterization, and cytotoxicity studies of novel anti-tubercular agent-loaded liposomal vesicles.

The treatment of tuberculosis is still a challenging process due to the widespread of pathogen strains resistant to antibacterial drugs, as well as the undesirable effects of anti-tuberculosis therapy. Hence, the development of safe and effective new anti-antitubercular agents, in addition to suitable nanocarrier systems, has become of utmost importance and necessity. Our research aims to develop liposomal vesicles that contain newly synthesized compounds with antimycobacterial action. The compound being studied is a derivative of imidazo-tetrazine named 3-(3,5-dimethylpyrazole-1-yl)-6-(isopropylthio) imidazo [1,2-b] [1,2,4,5] tetrazine compound. Several factors that affect liposomal characteristics were studied. The maximum encapsulation efficiency was 53.62 ± 0.09. The selected liposomal formulation T8* possessed a mean particle size of about 205.3 ± 3.94 nm with PDI 0.282, and zeta potential was + 36.37 ± 0.49 mv. The results of the in vitro release study indicated that the solubility of compound I was increased by its incorporation in liposomes. The free compound and liposomal preparation showed antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) at MIC value 0.94-1.88 µg/ml. We predict that the liposomes may be a good candidate for delivering new antitubercular drugs.

Application of the Ugi reaction for preparation of submicron capsules based on sugar beet pectin.

The Ugi four-component condensation in diluted liposomal suspensions was used to prepare pectin-based submicron capsules. A set of isocyanides and aldehydes was used to optimize the synthesis of capsule shells. Modified sugar beet pectin was selected as a natural polymer with pronounced surface activity to create a capsule shell. At first, liposomal composition was optimized in order to select suitable conditions for capsule formation. Then, the wide set of capsules constructed on modified sugar beet pectin scaffold has been synthesized. The choice was determined by level of substitution degree and possible chemical diversity of the modified surface. Detailed characterization of products has been performed for polysaccharide particles with liposomal core prepared with various processing parameters (concentration, cross-linking components, the density of linkage). The chemical structure, average size, polydispersity index, morphology, stability, and cytotoxicity of obtained particles have been investigated in dependence on the shell content. The obtained submicrometer cross-linked capsules (220-240 nm) with controlled colloidal properties showed high stability and low toxicity. Thus, the proposed carriers have a great potential as sustained drug delivery systems for different administration routes.

Preparation of chitosan-coated liposomes as a novel carrier system for the antiviral drug Triazavirin.

Novel method for the coating of positively charged liposomes with modified chitosan was elaborated. Liposomes were prepared by stepwise extrusion through inorganic membranes (Anotop) of 0.2 and 0.1 µm pore sizes. Chitosan derivatives were synthesized via the Ugi multicomponent reaction. Several series of liposomal compositions were produced and their properties were compared in terms of particle size, polydispersity index (PDI), zeta potential and stability. The effect of various additives was investigated and the optimal composition of the lipid film was determined. The addition of the uncharged fatty esters allowed the diameter of the liposomes obtained by extrusion to be reduced to 145-150 nm with a PDI of 0.13-0.15. The prepared liposomes were loaded with the novel antiviral drug Triazavirin and used to determine the release profile. Triazavirin was included into liposome layer as a salt with biocompatible choline derivatives of limiting fatty acids. The appropriate lipid composition was used for the preparation of a larger quantity of liposomes coated by modified chitosan. It was shown that an appropriate combination of liposomes and polysaccharide layer potentially extended colloidal stability by up to 3 months and exhibited broad functional capabilities for surface modification.

Reaction of isocyanides with thiophenols and gem-diactivated olefins: a one-pot synthesis of substituted 2-aminopyrroles.

A novel multicomponent reaction of isocyanides with thiophenols and gem-diactivated olefins has been discovered. Depending on the choice of isocyanides, substituted 2-aminopyrroles or thioimidates have been prepared. The obtained scaffolds bearing four points of diversity can directly be used in combinatorial syntheses.

A novel three-component reaction designed by the combinatorial method: heteroarenes, isothiocyanates and isocyanides.

The novel three-component reaction of isoquinoline with isothiocyanates and isocyanides leads to a variety of new imidazoisoquinolines. The zwitterionic ground state of these new ring systems is established by means of NMR and X-ray analysis. Use of phthalazine instead of isoquinoline gives access to imidazole annulated phthalazines.

Ugi reaction in aqueous solutions: a simple protocol for libraries production.

A reaction between levulinic acid, isocyanides and primary amines has been examined in distilled water and in surfactants solutions. It is demonstrated that the reaction gives good results at the different concentrations including one well above the solubility limit. A simple and eco-friendly protocol for libraries production is described.