Pharmaceutical Chemistry Journal最新文献

The transdermal route is considered one of the most favourable routes of drug delivery over other conventional routes. The stratum corneum (SC) is the main barrier to the delivery of drugs by the transdermal route. Many strategies are employed to overcome SC barrier properties like lipid vesicles, permeation enhancers, physical methods, etc. The main objective of this research article was to explore and compare a few chemical penetration enhancers in combination with physical means like tape stripping and microneedle to enhance the transdermal permeation of caffeine. The transdermal gel of caffeine was prepared by dissolving the drug in distilled water containing various concentrations of chemical penetration enhancers, including Arlasolve DMI, ethanol, transcutol P and DMSO. Ex-vivo skin permeation and skin deposition studies were conducted on the transdermal gel alone and in combination with the microneedle or tape-stripping methods. The HPLC method analyzed the total amount of caffeine that permeated through the skin sample. The formulations containing Arlasolve DMI as a penetration enhancer showed the maximum drug penetration among all the penetration enhancers. A combination of microneedles with Arlasolve DMI showed the best skin permeation among all the methods tested. It was clear from the results that Arlasolve DMI would be a better option to use as a penetration enhancer in the dermatological formulations of caffeine in combination with a microneedle-based permeation enhancement method.

The new conjugate compound pyrrolylcarnosine was synthesized from the natural antioxidant carnosine and the aromatic five-membered nitrogen heterocycle pyrrole. The synthesis of pyrrolylcarnosine was described. Its physicochemical properties and biological activity in various oxidative stress models were evaluated. The results showed that pyrrolylcarnosine was characterized by resistance to hydrolysis by serum carnosinase and exhibited high antioxidant activity in model experiments. It had a neuroprotective effect under oxidative stress induced by the neurotoxin AAPH, increasing the viability of a differentiated culture of human neuroblastoma SH-SY5Y and protecting it from death. In general, the results indicated creation of a new drug based on pyrrolylcarnosine was promising.

In the area of drug development the solubility of an active ingredient plays a very crucial and vital part and is of the highest significance. Increasing importance is being placed on the research into active ingredient solubilization. The designing of a host guest complex with a compound that has a higher dissolubility profile can work with the solubilization of lipophilic drugs. In this research work optimized nano-carriers were effectively synthesized utilizing thin-film hydration strategies. The drug sulfonated calix[4]resorcinarene blend (1:10) containing ethanol was dispersed and sonicated with an estimated three cycles, at an amplitude 70 with a 20-s interval for an optimized time. The synthesized nanovesicles have an average diameter of 477.7 nm, a higher mono dispersity (PDI-0.282), and a greater loading capacity of the drugs is 95%. Atomic force microscopy in accordance with dynamic light-scattering spectra confirmed the spherical shape of paclitaxel-loaded sulfonated calix[4]resorcinarene nanovesicles. In vitro release of medication from nanovesicles affirmed the extended discharge pattern of drugs with r² of 0.9902 compared with the commercial formulation available on the market. MTT assay is performed to access the toxicity of the sufonated calix[4]resorcinarene in vitro. IC₅₀ values indicate that synthesized sufonated calix[4]resorcinarene shows better IC₅₀ values than paclitaxel and taxol. The formulated nanovesicles from sulfonated calix[4]resorcinarene showed an ideal size with higher capacity for binding drug and provide better patient compliance, which are positive for their expected application as a modular drug delivery platform for anti-cancer drugs.

The purpose of the present research was to study peculiarities in the accumulation of natural and artificial radioisotopes in medicinal plant raw material using nettle (Urtica dioica L.) leaves as an example. The specific activities of the main long-lived artificial radioisotopes (cesium-137 and strontium-90) and naturally occurring radionuclides (thorium-232, potassium-40, and radium-226) in experimental samples of upper soil layers and nettle leaves were determined on a RADEK MKGB-01 spectrometer-radiometer. All studied samples of nettle leaves collected in natural and artificial phytocenoses of Voronezh Region met existing radiation safety requirements (first group). A correlation analysis of the specific activities of artificial and natural radionuclides in the soil and nettle leaves showed a close relationship between these numerical indicators that confirmed their contamination primarily through soil. The specific activities of strontium-90, cesium-137, thorium-232, potassium-40, and radium-226 in the medicinal plant raw material increased as their specific activities in the soil increased. High accumulations of cesium-137 and potassium-40 from the upper soil layers were noted for nettle leaves growing in Voronezh Region. A detailed analysis of the dependence of the calculated accumulation coefficients of natural and artificial radioisotopes in nettle leaves revealed trends toward their decrease with increases in the specific activities of the radionuclides in the soil, which indicated physical mechanisms for regulating their uptake into the plant were present.

A simple and promising methodology was employed for the synthesis of (Z)-1-(benzo[d]thiazol-2-yl)-2-(3-substituted thiazolidine-4-one) hydrazine as antitubercular agents. In vitro activity was tested against Mycobacterium tuberculosis. Two derivatives among all the synthesized compounds were found to be highly effective. Furthermore, to rationalize the observed biological activity data, a molecular docking study has also been carried out against a potential target DprE1 enzyme. The interaction was shown between the oxygen of thiazolidinediones and Ser228. The bond distance (O—H) is 2.35 Å. The π-π-stacking was seen between His137 and thiazole ring electrons. The binding score of compound 15 is –7 kcal/mol, which suggests an excellent binding affinity toward the Dpre1 receptor.

The article focused on a study of the release of melanin from its gel dosage form and the toxicological properties of the gel. The recorded release of melanin from the gel was fastest during the first 3 h (50.8%). The remaining amount of melanin was subsequently released gradually as the system equilibrium shifted. The photoprotective action of the drug was prolonged because of the slowed melanin release. Symptoms of acute toxicosis and lethal outcomes were not recorded in all experimental animals during studies of the acute toxicity parameters of the developed gel based on melanin isolated from horse chestnut seed episperm with subcutaneous administration and cutaneous application at doses of 1500, 2000, 2500, and 3000 mg/kg. The developed photoprotective gel belonged to class Vof practically harmless substances. The LD₅₀ value for cutaneous application to rats was >2500 mg/kg.

Gout arthritis is an inflammatory arthritis characterized by increased serum uric acid and accumulation of monosodium urate (MSU) crystals in soft tissues. The treatment for gout arthritis is centered on reducing uric acid agents with long-term and anti-inflammatory agents during attack times. In recent studies, it is noteworthy that Indomethacin and Dexamethasone have positive effects in the treatment of gout. Dimethyl sulfoxide (DMSO) is a lipophilic solvent and has an anti-inflammatory effect at appropriate doses. Based on this information, for this study, the effects of these three agents were investigated in rats using a gut model to compare their efficacy. In the study, a total of 48 female 3–4-month rats were divided equally into 8 groups: Control, Indomethacin, DMSO, Dexamethasone, Gout, Gout+Indomethacin, Gout+DMSO, Gout +Dexamethasone. During the eight-week study, a gout arthritis model was used that included 10 mg MSU given intra-articularly in the right foot. Indomethacin 12.5 mg/kg intragastric, DMSO 0.1 ml intraperitoneally and dexamethasone 0.2 mg/kg were administered subcutaneously to the related groups once a day for seven days. At the end of the study, collected articular tissues were stained with haematoxylin and eosin after the fixation and decalcification processes were done. The findings obtained showed that inflammation was reduced in treatment groups compared to the Control groups (all p values 0.002). Also, synovial proliferation was remarkably decreased in the Gout+Dexamethasone group compared to the Gout group (p = 0.019). As a result of these findings, although the three agents all reduced inflammation in gout arthritis, DMSO was shown to be more advantageous due to its having fewer side-effects.

The availability of piperidine, which is widely used for deblocking α-amine groups in solid-phase peptide synthesis using Fmoc methodology, is now significantly limited because this reagent is classified as a controlled substance. Therefore, a search for other available reagents capable of removing Fmoc-protection seems relevant. The suitability of three deblocking reagents based on secondary amines (4-methylpiperidine, pyrrolidine, and piperazine) for the solid-phase synthesis of peptides of various structures, i.e., atosiban (an analog of the neurohypophysial hormone oxytocin), metilin [an agonist of the apelin receptor (APJ)], and a fragment of the 11-19 amino-acid segment of the regulatory myosin light chain was comparatively assessed. These reagents were shown to be suitable alternatives to piperidine for the preparation of the physiologically active peptides being studied.

A method for microextraction recovery and concentration of tilmicosin phosphate in washings from surfaces of pharmaceutical equipment for its determination by high-performance liquid chromatography with spectrophotometric detection was proposed. The developed method involved dispersion of the extractant (1-dodecanol) in an aqueous solution of a sample while rotating a cotton disk equipped with an inserted magnetic stirrer followed by crystallization of the extract upon cooling the extraction system. The extractant was applied beforehand to the cotton disk. Effective dispersion of the extractant in the aqueous phase during rotation of the cotton disk ensured a high degree of analyte recovery (94%). The detection limit of tilmicosin phosphate (3σ) reached 0.7 mg/L. The determined concentrations ranged from 2 to 250 mg/L. The analytical capabilities of the developed method were demonstrated using quantitative determination of tilmicosin phosphate in washings from surfaces of pharmaceutical equipment after completion of its cleaning as examples.

The composition and technology for obtaining a solid dosed stable dosage form of a promising representative of the class of nitrogen monoxide (NO) donors, an anionic tetranitrosyl iron complex with thiosulfate ligands Na₂[Fe₂(S₂O₃)₂(NO)₄]·4H₂O, were developed. The rate of NO generation by the complex could be modulated by using different types of excipients or by varying their concentrations. Albumin was found to be the optimal prolonging agent in the manufacture of this dosage form. The developed dosage form expanded the arsenal of long-acting NO-donor medicines used to treat socially significant diseases.