Cataleptogenic effect of haloperidol formulated in water-soluble calixarene-based nanoparticles

In this study, a water-soluble form of haloperidol was obtained by coaggregation with calix[4]resorcinol bearing viologen groups on the upper rim and decyl chains on the lower rim to form vesicular nanoparticles. The formation of nanoparticles is achieved by the spontaneous loading of haloperidol into the hydrophobic domains of aggregates based on this macrocycle. The mucoadhesive and thermosensitive properties of calix[4]resorcinol–haloperidol nanoparticles were established by UV-, fluorescence and CD spectroscopy data. Pharmacological studies have revealed low in vivo toxicity of pure calix[4]resorcinol (LD50 is 540 ± 75 mg/kg for mice and 510 ± 63 mg/kg for rats) and the absence of its effect on the motor activity and psycho-emotional state of mice, which opens up a possibility for its use in the design of effective drug delivery systems. Haloperidol formulated with calix[4]resorcinol exhibits a cataleptogenic effect in rats both when administered intranasally and intraperitoneally. The effect of the intranasal administration of haloperidol with macrocycle in the first 120 min is comparable to the effect of commercial haloperidol, but the duration of catalepsy was shorter by 2.9 and 2.3 times (p < 0.05) at 180 and 240 min, respectively, than that of the control. There was a statistically significant reduction in the cataleptogenic activity at 10 and 30 min after the intraperitoneal injection of haloperidol with calix[4]resorcinol, then there was an increase in the activity by 1.8 times (p < 0.05) at 60 min, and after 120, 180 and 240 min the effect of this haloperidol formulation was at the level of the control sample

Novel Schiff Bases of C-Methylresorcinarene Derivatives

The article presents the synthesis and properties of two new Schiff bases of resorcinarene derivatives. The Schiff bases were obtained by the reaction of formylresorcinarene with aromatic (o-aminophenol) and aliphatic (N,N-dimethyldiaminoethane) amines in chloroform. The synthesized Schiff bases exist in equilibrium of several tautomers, as evident from the IR, UV, NMR spectra and cyclic voltammetry data analysis. In DMF, methanol, and acetonitrile, the tautomeric equilibrium is shifted toward the enol-imine tautomers

Interaction of mucin with viologen and acetate derivatives of calix[4]resorcinols

The mucus layer acts as a selective diffusion barrier that has an important effect on the efficiency of drug delivery systems in the human body. In this regard, currently the drug nanocarriers of various sizes and compositions are being widely developed to study their mucoadhesive properties i.e., the ability to interact with mucin. However, the effective interaction of drug composition with mucin does not guarantee the success due to the fact that there is a further barrier in the form of epithelial cells retained by calcium ions under the mucus layer. In this work, the interaction of mucin (porcine gastric mucin) with calixarenes is considered for the first time. The study of interaction between calixarenes, mucin and calcium ions by a complex of physicochemical methods showed that effective interaction with mucin requires cationic fragments, and binding with calcium is realized due to anionic fragments in the calixarene structure. Therefore, the combination of different chemical groups in the structure of drug nanocarrier plays an important role in successful mucosal drug delivery. Taking into account the wide possibilities of synthetic modification of the macrocyclic platform, calixarenes can find the application in the drug delivery across mucous barriers

Synthesis of 6-Methyluracilpentylviologen Resorcinarene Cavitand

Resorcinarenes, as macrocyclic compounds, are widely used to recognize substrates and create supramolecular assemblies. Their bowl-like form organizes functional groups at the upper and lower rims, which has a substantial impact on the molecular recognition of various substrates. As a result, resorcinarenes make good drug nanocarrier candidates. This paper presents the synthesis of a new resorcinarene cavitand functionalized along the upper rim with methyluracil and viologen fragments for its potential use in drug delivery. Methyluracils and viologens are well-known receptor-targeted compounds capable of facilitating the vector transfer of drugs and increasing the effectiveness of their action on cells. The paper describes the synthesis of resorcinarene modified with methyluracil and viologen groups along with its structure determined by 1H-, 13C-NMR and IR spectroscopy

Closed polymer containers based on phenylboronic esters of resorcinarenes

Novel polymer nanospheres (p(SRA-B)) were prepared by cross-linking a sulfonated resorcinarene (SRA) with phenylboronic acid. p(SRA-B) shows good stability in water and can be used as a nanocontainer for the pH- and glucose-controlled substrate release. Fluorescent dyes (fluorescein, pyrene and 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt) were successfully loaded into p(SRA-B). The release of dye is achieved by lowering the pH value to 3 or by adding glucose

Thymine-Modified Nanocarrier for Doxorubicin Delivery in Glioblastoma Cells

Brain tumor glioblastoma is one of the worst types of cancer. The blood–brain barrier prevents drugs from reaching brain cells and shields glioblastoma from treatment. The creation of nanocarriers to improve drug delivery and internalization effectiveness may be the solution to this issue. In this paper, we report on a new nanocarrier that was developed to deliver the anticancer drug doxorubicin to glioblastoma cells. The nanocarrier was obtained by nanoemulsion polymerization of diallyl disulfide with 1-allylthymine. Diallyl disulfide is a redox-sensitive molecule involved in redox cell activities, and thymine is a uracil derivative and one of the well-known bioactive compounds that can enhance the pharmacological activity of doxorubicin. Doxorubicin was successfully introduced into the nanocarrier with a load capacity of about 4.6%. Biological studies showed that the doxorubicin nanocarrier composition is far more cytotoxic to glioblastoma cells (T98G) than it is to cancer cells (M-HeLa) and healthy cells (Chang liver). The nanocarrier improves the penetration of doxorubicin into T98G cells and accelerates the cells’ demise, as is evident from flow cytometry and fluorescence microscopy data. The obtained nanocarrier, in our opinion, is a promising candidate for further research in glioblastoma therapy