Skin burns and ulcers are considered hard-to-heal wounds due to their high infection risk. For this reason, designing new options for wound dressings is a growing need. The objective of this work is to investigate the properties of poly (ε-caprolactone)/poly (vinyl-pyrrolidone) (PCL/PVP) microfibers produced via electrospinning along with sorbents loaded with Argovit™ silver nanoparticles (Ag-Si/Al₂O₃) as constituent components for composite wound dressings. The physicochemical properties of the fibers and sorbents were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and inductively coupled plasma optical emission spectroscopy (ICP-OES). The mechanical properties of the fibers were also evaluated. The results of this work showed that the tested fibrous scaffolds have melting temperatures suitable for wound dressings design (58–60 °C). In addition, they demonstrated to be stable even after seven days in physiological solution, showing no macroscopic damage due to PVP release at the microscopic scale. Pelletized sorbents with the higher particle size demonstrated to have the best water uptake capabilities. Both, fibers and sorbents showed antimicrobial activity against Gram-negative bacteria Pseudomona aeruginosa and Escherichia coli, Gram-positive Staphylococcus aureus and the fungus Candida albicans. The best physicochemical properties were obtained with a scaffold produced with a PCL/PVP ratio of 85:15, this polymeric scaffold demonstrated the most antimicrobial activity without affecting the cell viability of human fibroblast. Pelletized Ag/Si-Al₂O₃-3 sorbent possessed the best water uptake capability and the higher antimicrobial activity, over time between all the sorbents tested. The combination of PCL/PVP 85:15 microfibers with the chosen Ag/Si-Al₂O₃-3 sorbent will be used in the following work for creation of wound dressings possessing exudate retention, biocompatibility and antimicrobial activity.

BT44 is a novel, second-generation glial cell line-derived neurotropic factor mimetic with improved biological activity and is a lead compound for the treatment of neurodegenerative disorders. Like many other small molecules, it suffers from intrinsic poor aqueous solubility, posing significant hurdles at various levels for its preclinical development and clinical translation. Herein, we report a poly(2-oxazoline)s (POx)-based BT44 micellar nanoformulation with an ultrahigh drug-loading capacity of 47 wt %. The BT44 nanoformulation was comprehensively characterized by ¹H NMR spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), dynamic light scattering (DLS), and cryo-transmission/scanning electron microscopy (cryo-TEM/SEM). The DSC, XRD, and redispersion studies collectively confirmed that the BT44 formulation can be stored as a lyophilized powder and can be redispersed upon need. The DLS suggested that the redispersed formulation is suitable for parenteral administration (D_h ≈ 70 nm). The cryo-TEM measurements showed the presence of wormlike structures in both the plain polymer and the BT44 formulation. The BT44 formulation retained biological activity in immortalized cells and in cultured dopamine neurons. The micellar nanoformulation of BT44 exhibited improved absorption (after subcutaneous injection) and blood-brain barrier (BBB) penetration, and no acute toxic effects in mice were observed. In conclusion, herein, we have developed an ultrahigh BT44-loaded aqueous injectable nanoformulation, which can be used to pave the way for its preclinical and clinical development for the management of neurodegenerative disorders.

Parkinson’s disease (PD) is the most common age-related movement disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons. To date, PD treatment strategies are mostly based on dopamine replacement medicines, which can alleviate motor symptoms but do not slow down the progression of neurodegeneration. Thus, there is a need for disease-modifying PD therapies. The aim of this work was to evaluate the neuroprotective effects of the novel compound PA96 on dopamine neurons in vivo and in vitro, assess its ability to alleviate motor deficits in MPTP- and haloperidol-based PD models, as well as PK profile and BBB penetration. PA96 was synthesized from (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl) cyclohex-3-ene-1,2-diol (Prottremin) using the original three-step stereoselective procedure. We found that PA96: (1) supported the survival of cultured näive dopamine neurons; (2) supported the survival of MPP⁺-challenged dopamine neurons in vitro and in vivo; (3) had chemically appropriate properties (synthesis, solubility, etc.); (4) alleviated motor deficits in MPTP- and haloperidol-based models of PD; (5) penetrated the blood–brain barrier in vivo; and (6) was eliminated from the bloodstream relative rapidly. In conclusion, the present article demonstrates the identification of PA96 as a lead compound for the future development of this compound into a clinically used drug.

Recombinant human interferon alpha-2b (rIFN) is widely used in antiviral and anticancer immunotherapy. However, the high efficiency of interferon therapy is accompanied by a number of side effects; this problem requires the design of a new class of interferon molecules with reduced cytotoxicity. In this work, IFN was modified via genetic engineering methods by merging it with the blood plasma protein apolipoprotein A-I in order to reduce acute toxicity and improve the pharmacokinetics of IFN. The chimeric protein was obtained via biosynthesis in the yeast P. pastoris. The yield of ryIFN-ApoA-I protein when cultivated on a shaker in flasks was 30 mg/L; protein purification was carried out using reverse-phase chromatography to a purity of 95–97%. The chimeric protein demonstrated complete preservation of the biological activity of IFN in the model of vesicular stomatitis virus and SARS-CoV-2. In addition, the chimeric form had reduced cytotoxicity towards Vero cells and increased cell viability under viral load conditions compared with commercial IFN-a2b preparations. Analysis of the pharmacokinetic profile of ryIFN-ApoA-I after a single subcutaneous injection in mice showed a 1.8-fold increased half-life of the chimeric protein compared with ryIFN.

Современные технологии и уровень фундаментальных исследований позволяют создавать медицинские сорбенты с заранее определенными структурными, прочностными и адсорбционными свойствами. Сорбционные материалы интересны не только в роли детоксикантов, используемых для удаления токсических агентов из жидких сред, но и в качестве носителей для доставки в зоны терапевтического воздействия биологически активных веществ. Целью работы является обоснование состава полифункционального препарата с антибактериальным и детоксикационным эффектами за счет комплекса серебра и сорбционной составляющей – алюмо-кремний содержащего сорбента. Материалы и методы. В работе использовали физико-химические (сорбционная активность красителя метиленового синего, удельная поверхность, водородный показатель при контакте с водой, атомноэмиссионная спектрометрия с индуктивно-связанной плазмой) и фармацевтические методы (насыпная плотность, растворение для твердых дозированных лекарственных форм исследования). Результаты и обсуждение. Обоснован двухстадийный способ иммобилизации комплекса серебра и гидрофобизатора на поверхность сорбционной матрицы. Выделен образец оптимального состава серебросодержащего препарата: оксид – гидроксид алюминия – 99,2%, кластерное серебро (Арговит – С 2%) – 0,3% в расчете на серебро и вспомогательное вещество (гидрофобизатор – ПМС марка П – 841) – 0,5%. Выход серебра в раствор из образца указанного состава за 8 часов не превышал 1,6 ± 0,3%, величина удельной поверхности – 90 м2/г, величина водородного показателя – 8,1 ± 0,02, насыпная плотность – 1,12 ± 0,11 г/см3. Заключение. В работе экспериментально обоснован состав серебросодержащего препарата AlSi/Ag, получены комплексные научные данные о его физико-химических, технологических особенностях.

The aim of this work is to study the effect of agents combining fragments of monoterpenoids and 3,7diazabicyclo[3.3.1]nonane (bispidine) on the performance of mice. Physical endurance was studied using two tests: exhaustive swimming with a load of 7% of body weight (after single dosing) and exhaustive treadmill running (after single dosing and a 7-day administration). It has been shown for the first time that derivatives of monoterpenoids with 3,7-diazabicyclo[3.3.1]nonane moiety containing methyl substituents at positions 1 and 5 have a stimulatory effect on the performance of mice, which exceeds the effect of the reference drug bromantane after single dosing. Compound K1-458, which contains (-)-myrtenal residues linked to a bispidine fragment via amino groups, is the most effective in increasing the duration of running and swimming at a dose of 100 mg/kg after single intragastric administration. It has been also established that the LD50 for these compounds exceeds 1,000 mg/kg.