Polimery w medycynie最新文献

Background: Dapsone (DAP) is an anti-inflammatory and antimicrobial active pharmaceutical ingredient used to treat, e.g., AIDS-related diseases. However, low solubility is a feature hampering its efficient use.

Objectives: First, deep eutectic solvents (DES) were used as solubilizing agents for DAP as an alternative to traditional solvents. Second, intermolecular interactions in the systems were described and quantified. Finally, the solubility prediction model, previously created using the machine learning protocol, was extended and improved using new data obtained for eutectic systems.

Material and methods: New DES were created by blending choline chloride (ChCl) with 6 selected polyols. The solubility of DAP in these solvents was measured spectrophotometrically. The impact of water dilution on the solubility curve was investigated. Experimental research was enriched with theoretical interpretations of intermolecular interactions, identifying the most probable pairs in the systems. Dapsone self-association and its ability to interact with components of the analyzed systems were considered. Thermodynamic characteristics of pairs were utilized as molecular descriptors in the machine learning process, predicting solubility in both traditional organic solvents and the newly designed DES.

Results: The newly formulated solvents demonstrated significantly higher efficiency compared to traditional organic solvents, and a small addition of water increased solubility, indicating its role as a co-solvent. The interpretation of the mechanism of DAP solubility highlighted the competitive nature of self-association and pair formation. Thermodynamic parameters characterizing affinity were instrumental in developing an efficient model for theoretical screening across diverse solvent classes. The study emphasized the necessity of retraining models when introducing new experimental data, as exemplified by enriching the model with data from DES.

Conclusions: The research showcased the efficacy of developing new DES for enhancing solubility and creating environmentally and pharmaceutically viable systems, using DAP as an example. Molecular interactions proved valuable in understanding solubility mechanisms and formulating predictive models through machine learning processes.

Background: One of the important formalisms of non-equilibrium thermodynamics is Peusner network thermodynamics. The description of the energy conversion in membrane processes, i.e., the conversion of the internal energy of the system into the dissipated energy and the free energy used for the work associated with the transport of solution components, allows us to describe the relationship between these energies and the thermodynamic forces acting in the membrane system.

Objectives: The aim of this study was to develop a procedure to transform the Kedem-Katchalsky equations for the transport of binary electrolytic solutions across a membrane into the Kedem-Katchalsky-Peusner equations based on Peusner network thermodynamics. The conversion of electrochemical energy to free energy in the membrane system was also determined.

Material and methods: The nanobiocellulose biomembranes (Biofill) were the subject of the study with experimentally determined transport parameters for aqueous NaCl solutions. The research method is the Kedem-Katchalsky-Peusner formalism for binary electrolyte solutions with introduced Peusner coefficients.

Results: The coefficients of the L version of the membrane transport equations and the Peusner coupling coefficients were derived as functions of NaCl concentration in the membrane. Based on these coefficients, the fluxes of internal energy of the system, energy dissipated to the surroundings and free energy related to the transport of electrolyte across the membrane were calculated and presented as functions of the osmotic and electric forces on the membrane.

Conclusions: The Peusner coefficients obtained from the transformations of the coefficients of the Kedem-Katchalsky formalism for the transport of electrolyte solutions through the Biofill membrane were used to calculate the coupling coefficients of the membrane processes and the dissipative energy flux. The dissipative energy flux takes the form of a quadratic form due to the thermodynamic forces on the membrane - second degree curves are obtained. Moreover, the dissipative energy flux as a function of thermodynamic forces allowed us to examine the energy conversion in transport processes in the membrane system.

Background: Today's growing demand for advanced and sustainable polyester materials is driven by an increasing awareness of the environmental impact of traditional materials, emphasizing the need for eco-friendly alternatives. Sustainability has become central in materials development, including the biomedical area, where biobased and environmentally friendly solutions are a rapidly growing field.

Objectives: This research aims to comprehensively evaluate a new enzymatically catalyzed furan-based copolymer, poly(decamethylene furanoate)-co-(dilinoleic furanoate) (PDF-DLF), with a 70-30 wt% hard-to-soft segment ratio. Then, its performance across medical applications is explored, with a particular focus on its potential as a nanofibrous scaffolding material.

Material and methods: PDF-DLF was synthesized from biobased monomers using Candida antarctica lipase B (CAL-B) as the biocatalyst. Material characterization included dynamic mechan‑ical thermal analysis (DMTA) to assess the mechanical behavior and thermal properties. Enzymatic degradation studies determined biodegradability, while cytotoxicity tests established in vitro biocompatibility. The copolymer was electrospun into nanofibers, with scanning electron microscopy (SEM) employed to analyze their morphology.

Results: PDF-DLF displays mechanical and thermal properties indicating high storage modulus and 2 main temperature transitions. Enzymatic degradation studies and cytotoxicity assessments confirm biodegradability and in vitro biocompatibility. Electrospinning successfully transformed the copolymer into nanofibers with diameters ranging from 500 nm to 700 nm.

Conclusions: This study significantly advances our understanding of sustainable polyesters with versatile processing capabilities. The successful electrospinning highlights its potential as a biodegradable scaffold for medical engineering, supported by biocompatibility and sufficient mechanical properties. It opens new opportunities for sustainable materials in critical biomedical industries, including tissue engineering.

Background: There is a lack of studies evaluating the toxicity of nitric oxide (NO) precursors in chitosan/L-arginine hydrogels and their topical administration. However, clarifying the characteristics of these elements is essential for their possible use in non-surgical techniques of tooth movement acceleration. Such characteristics include interaction with different cell types, metabolism and drug safety.

Objectives: This in vitro study aimed to assess the cytotoxicity of chitosan hydrogels on human HeLa cells using different concentrations of L-arginine.

Material and methods: The hydrogels were synthesized in a materials engineering laboratory, with a controlled environment, using 4 different L-arginine concentrations of 0%, 10%, 15%, and 20%. Once the hydrogels were prepared, their physical and chemical properties were characterized, and viability analysis was performed using 2 different methods, including a 48-h assay with Artemia salina nauplii and a 24-h cell culture with human HeLa cells followed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay. Data analysis was performed using a Mann-Whitney U test to evaluate positive and negative controls in the cell culture, with a significance level of 0.01. A Wilcoxon paired test contrasted the 24-h compared to 48-h Artemia salina assays, with a Kruskal-Wallis and post hoc Dunn test used to compare groups using a significance level of 0.05.

Results: In the more viscous hydrogels, Artemia salina nauplii decreased drastically in 24 h, while the 15% and 20% hydrogels had no statistical differences from the negative control. The 10% and 20% hydrogels were statistically different from the negative control when comparing cell culture data.

Conclusions: Our findings suggest that chitosan/L-arginine hydrogels could be used in humans without toxic effects. However, more trials and tests are needed to evaluate tooth movement rate during orthodontic treatment.

Background: Solubility is a fundamental physicochemical property of active pharmaceutical ingredients. The optimization of a dissolution medium aims not only to increase solubility and other aspects are to be included such as environmental impact, toxicity degree, availability, and costs. Obtaining comprehensive solubility characteristics of chemical compounds is a non-trivial and demanding process. Therefore, support from theoretical approaches is of practical importance.

Objectives: This study aims to examine the accuracy of the reference solubility approach in the case of sulfanilamide dissolution in a variety of binary solvents. This pharmaceutically active substance has been extensively studied, and a substantial amount of solubility data is available. Unfortunately, using this set of data directly for theoretical modeling is impeded by noticeable inconsistencies in the published solubility data. Hence, this aspect is addressed by data curation using theoretical and experimental confirmations.

Material and methods: In the experimental part of our study, the popular shake-flask method combined with ultraviolet (UV) spectrophotometric measurements was applied for solubility determination. The computational phase utilized the conductor-like screening model for real solvents (COSMO-RS) approach.

Results: The analysis of the results of solubility calculations for sulfonamide in binary solvents revealed abnormally high error values for acetone-ethyl acetate mixtures, which were further confirmed with experimental measurements. Additional confirmation was obtained by extending the solubility measurements to a series of homologous acetate esters.

Conclusions: Our study addresses the crucial issue of coherence of solubility data used for many theoretical inquiries, including parameter fitting of semi-empirical models, in-depth thermodynamic interpretations and application of machine learning protocols. The effectiveness of the proposed methodology for dataset curation was demonstrated for sulfanilamide solubility in binary mixtures. This approach enabled not only the formulation of a consistent dataset of sulfanilamide solubility binary solvent mixtures, but also its implementation as a qualitative tool guiding rationale solvent selection for experimental solubility screening.

The eye is the most accessible site for topical drug delivery. Drug's ocular bioavailability is quite low when administered topically as eye drops. Viscosity enhancers are used to increase ocular bioavailability by extending the precorneal residence time of the drug at the ocular site. Cellulose, polyalcohol and polyacrylic acid are examples of hydrophilic viscosity enhancers. The addition of viscosity modifiers increases the amount of time the drug is in contact with the ocular surface. Several polysaccharides have been studied as excipients and viscosity boosters for ocular formulations, including cellulose derivatives such as chitosan (CS), xyloglucan and arabinogalactan (methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose). Viscosity-increasing substances reduce the surface tension, extend the corneal contact time, slow the drainage, and improve the bioavailability. Chitosan is a viscosity enhancer that was originally thought to open tight junction barrier cells in the epithelium. Chitosan thickens the medication solution and allows it to penetrate deeper. Alginate is an anionic polymer with carboxyl end groups that has the highest mucoadhesive strength and is used to improve penetration. Carboxymethylcellulose (CMC), a polysaccharide with a high molecular weight, is one of the most common viscous polymers used in artificial tears to achieve their longer ocular surface residence period. Hyaluronic acid (HA) is biocompatible and biodegradable in nature, and it is available in ocular sustained-release dose forms. A polymer known as xanthan gum is used to increase viscosity. At 0.2% concentration, carbomer forms a highly viscous gel.

Background: Microand nanoplastics pollution can cause substantial damage to ecosystems. Since scientists have focused mainly on their impact on aquatic environments, less attention has been paid to the accumulation of polymer particles in terrestrial organisms.

Objectives: We checked if submicron (<5 mm) polystyrene (PS) particles, which can accumulate in living organisms, lead to changes in the physicochemical properties of mammalian cell membranes.

Material and methods: The influence of submicron PS particles on the properties of rat-derived L6 myocytes and H9c2 cardiomyocytes was analyzed. Non-functionalized and amine-functionalized PS particles of 100 nm and 200 nm in diameter were used. The MTT assay was performed to evaluate the viability of the polymers-treated cells. The effect of short (6 h) and prolonged (48 h) incubation with different concentrations of PS particles on the cell's zeta (ζ) potential was examined with the electrophoretic light scattering technique (ELS). Polystyrene particles' physicochemical characteristics (size and stability) were performed using dynamic light scattering (DLS) and electrophoretic light scattering methods.

Results: The results show that submicron PS particles affect cell viability and cause changes in the physiochemical parameters of rat cell membranes. Differences were observed depending on the origin of the cells. We observed doseand time-dependent alterations in the studied parameters after submicron PS particle incubation in L6 myotubes and H9c2 cardiomyocytes.

Conclusions: The size and modification of PS particle surfaces determine the extent to which they affect the analyzed properties of rat cardiomyocytes and myocytes membranes.

In dentistry, fluoride compounds play a very important role in the development of teeth hard tissue. They have been modifying the development of the carious process for many years in accordance with the principles of minimally invasive therapy. Studies have confirmed their effectiveness in the prevention and treatment of carious lesions and erosion of deciduous and permanent teeth, as well as in the dentin hypersensitivity treatment. Typically, each varnish consists of 3 basic components, i.e., a resin usually in the form of mastic, shellac and/or rosin, an alcohol-based organic solvent (usually ethanol) and active agents. In the first-generation varnishes, the active agent is fluorine compounds, most often in the form of 5% NaF, while in second-generation varnishes, the composition is further enriched with calcium and phosphorus compounds in the form of CPP-ACP/CPP-ACPF, ACP, TCP, fTCP, CSPS, TMP, CXP, or CaGP. This influences the bioavailability of fluoride in the oral environment by increasing both its release from the product and its subsequent accumulation in enamel and plaque, promotes more efficient closure of dentinal tubules, and facilitates pH buffering in the oral cavity.

Over the years, exopolysaccharides (EPSs) have been utilized in various areas of research, including health, industry, environment, and agriculture, due to their flexible physical, chemical and structural properties that can be readily modified to suit desired purposes. Current research trends have shown that EPS production is dependent on numerous factors which can be combined to varying extent to optimize production yields. Although the majority of research is directed towards their industrial and medicinal uses, these chemical substances possess peculiar characteristics which are also exploited for biomedical research, where they are being used as drug delivery systems, some of which include their abundance in nature, biocompatibility, biodegradability, non-toxicity, and ability to efficiently encapsulate sensitive bioactive agents. However, despite the numerous beneficial prospects of microbial EPSs in drug delivery, there are limitations to the commercial production and industrial applications of these biopolymers. These limitations have inspired revolutionary research into the cost-effective production of safe EPSs polymers. In this review, we classify EPSs and discuss their methods of extraction and characterization. We also summarized current drug delivery applications and discussed limitations to extensive industrial commercialization of EPSs, while highlighting prospects for the utilization of microbial EPSs and implications for research.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with largely unknown pathogenesis and no effective cure. It is believed that several, not mutually exclusive mechanisms contribute to the pathogenesis and progression of this disease, including, among others, elevated oxidative stress, excitotoxicity, increased neuroinflammation, and protein aggregation. Receptor for advanced glycation end products (RAGE) is a part of immunoglobulin superfamily; it is believed to participate in ALS pathogenesis.

Objectives: Our previous studies on ALS demonstrated that RAGE is likely one of the key players in ALS, acting on its own and in tandem with its oxidative stress and pro-inflammatory ligands, such as advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs). In this study, based on our previous results, we aimed to establish blood levels of soluble RAGE, AGE and AOPP in ALS patients.

Material and methods: Forty-six coded and anonymized surplus plasma samples from ALS patients and non-neurological control were used in the study. The plasma levels of RAGE, AGE and AOPP were measured using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Statistical evaluation of data was performed using one-way non-parametric analysis of variance (ANOVA) with Kruskal-Wallis post hoc test.

Results: Our results revealed a decline in soluble RAGE level, concurrent with an increase in the levels of AGEs and AOPPs in blood samples from ALS patients, signifying a loss of neuroprotective form of RAGE and a simultaneous increase in AGE and AOPP production and uptake at the early stage of the disease.

Conclusions: The results obtained from our study indicate that further longitudinal study of RAGE, AGE and AOPP levels would be beneficial, outlining the dynamics between RAGE and its ligand levels as the disease progresses, and making them valuable diagnostic tools and potential therapeutic targets.