Polimery w medycynie最新文献

Background: Oral dissolving films are portable dosage forms that consist of active pharmaceutical ingredients incorporated into film-forming polymers such as starch. Starches obtain optimum filmogenic properties by gelatinization and blending with other polymers. The high starch content of bitter yam (Dioscorea dumetorum Pax) gives it yet unexplored potential for orodispersible films.

Objectives: This study aimed to investigate the effect of pregelatinization on the physicochemical properties of bitter yam starch. Additionally, our objective was to evaluate the potential of both native starch (NS) and pregelatinized starch (PS), incorporated into polymer blends, as biopolymeric materials for use in orally dissolving films (ODFs).

Material and methods: Native and pregelatinized wild Dioscorea dumetorum Pax (bitter yam) starch were prepared and characterized using physicochemical, microscopic and rheological methods, Fourier-transform infrared spectroscopy, X-ray diffractometry (XRD), and differential scanning calorimetry (DSC). Oral dissolving films with varying hydroxylpropylmethyl cellulose (HPMC)-to-starch ratios (1:1, 1:2 and 2:1) were formulated and evaluated based on organoleptic properties, surface morphology, folding endurance, weight and thickness, pH, and disintegration time.

Results: Pregelatinization improved the swelling, solubility and hydration capacity of the starch. Although no changes were observed in the crystalline nature upon gelatinization, DSC analysis revealed remarkable changes in the thermal behavior of the NS after pregelatinization. Both NS and PS did not produce continuous films without HPMC. Flexibility of the starch increased with increasing HPMC concentration films, and PS-based films had higher folding endurance compared to NS films. Native starch-based films had smoother surfaces and higher thicknesses than PS films. All the starch films demonstrated disintegration times longer than 15 min, and slightly acidic pH values.

Conclusions: Pregelatinization of bitter yam starch, followed by blending with HPMC at a 2:1 ratio, resulted in the most effective oral film formulation. Further studies focusing on optimizing disintegration rates and pH would help confirm the suitability of this starch for use in ODF formulations.

Background: Hepatitis C virus (HCV) causes long-term liver disease. Its capacity to influence the host immune system makes its pathogenesis more complicated. Targeting the IFITM3 gene presents a promising therapeutic strategy for treating HCV infections, as it blocks the virus from entering host cells.

Objectives: This study examines how HCV viral loads affect IFITM3 gene expression.

Material and methods: This study included 100 patient samples diagnosed with HCV through serological methods and confirmed as positive. Then, viral and human RNA were extracted using commercial kits. The viral RNA was then quantified using one-step real-time polymerase chain reaction (qPCR), enabling an accurate assessment of viral load in the blood. Following this, human RNA was converted to cDNA and quantified using qPCR to investigate IFITM3 gene expression.

Results: The distribution of blood groups among HCV-positive and HCV-negative samples showed that samples with the Oblood group had a significantly higher frequency of HCV positivity (18.4%) compared to the HCV-negative group (2.0%). Age analysis indicated a significant difference between HCV-positive and HCV-negative individuals with mean age of 37.8 ±1.48 years and 44.1 ±1.56 years, respectively. The expression levels of the IFITM3 gene were significantly higher in the HCV-positive group (4.21 ±1.17 fold) compared to the HCV-negative group (1.36 ±0.157 fold), with a p-value of 0.016. A correlation analysis between IFITM3 gene expression levels and HCV viral loads showed r-value of 0.343, indicating a moderate positive correlation, with p-value of 0.016.

Conclusions: Strong correlations observed in this study show the need for a comprehensive understanding and management approach to HCV disease. These relationships should be studied longitudinally to verify causality and assess potential interventions. IFITM3 gene expression as a biomarker for HCV infection and disease progression warrants further investigation.

Background: The results of numerous research studies published in recent years suggest that celecoxib (CEL) may be effective in the treatment of various skin disorders. However, to date, no semisolid product containing CEL has been launched.

Objectives: With a focus on the future development of topical products, we aimed to investigate the impact of different semisolid matrices on the in vitro performance of CEL.

Material and methods: For this purpose, 1% (w/w) of the drug was suspended in 4 compounding vehicles available in Polish community pharmacies: Lekobaza (amphiphilic cream), Lekobaza Lux (hydrophobic cream), Celugel (hydrogel), and Oleogel (lipogel). Given their very different physicochemical properties, our goal was to analyze, for the first time, their influence on spreadability, viscoelastic properties and the release rate of CEL.

Results: It was found that all of the semisolid matrices were suitable as vehicles for the drug in terms of spreadability and rheological stability. The viscous properties predominated when Celugel was used as a vehicle, but when Lekobaza, Lekobaza Lux and Oleogel were tested, the elastic properties prevailed. The drug release rate was the highest when hydrophilic matrices, i.e., Celugel or Lekobaza were used, but when hydrophobic matrices such as Lekobaza Lux or Oleogel were examined, CEL was released slowly. These findings might be related not only to the properties of these matrices, but also to the design of the release study that was more suitable for evaluating the hydrophilic matrices.

Conclusions: Celugel could be particularly useful as a vehicle for CEL for the therapy of large lesions with heavy exudation, but if there is a risk of skin drying out after using the hydrogel, the use of Lekobaza can be recommended.

Background: Polyhydroxybutyrate nanoparticles (PHB-NPs) represent a promising strategy for addressing the growing threat of bacterial resistance to antibiotics - a major concern in global public health. Despite their potential, there is a noticeable gap in the current literature regarding their ability to enhance the efficacy of existing antibiotic therapies.

Objectives: This study investigates the synergistic effect of PHB-NPs in enhancing the antibacterial activity of ceftriaxone (CRO) against Pseudomonas aeruginosa, with a particular focus on mitigating key virulence factors such as biofilm formation and adhesion.

Material and methods: Polyhydroxybutyrate nanoparticles were synthesized using the pH gradient and sonication method. The antibacterial activity of PHB-NPs, CRO and the combined formulation (PHB-NP-CRO) was assessed using minimum inhibitory concentration (MIC) testing and the well diffusion method. Additionally, the effects of these formulations on P. aeruginosa biofilm formation on an abiotic surface (polystyrene) and bacterial adhesion to human oral mucosal epithelial cells (OMECs) were evaluated.

Results: The diameters of the prepared PHB-NPs ranged from 15 nm to 34 nm, with an average size of 28.2 ±6.3 nm. All P. aeruginosa isolates were capable of biofilm production. A negative correlation was observed between the diameter of the CRO inhibition zones and the extent of biofilm formation among the 20 isolates. The MICs for PHB, PHB-NPs, CRO, and the combined formulation (PHB-NP-CRO) were 2,000, 1,000, 250, and 62.5 μg/mL, respectively. Sub-MIC concentrations (as low as 1/32 MIC) of both CRO and PHB-NP-CRO exhibited significant inhibitory effects on biofilm formation and bacterial adhesion to human OMECs (p < 0.050).

Conclusions: The combination of PHB-NPs with CRO significantly enhances the antibacterial activity of CRO against P. aeruginosa. Moreover, sub-inhibitory concentrations (sub-MICs) of both PHB-NP-CRO and CRO alone effectively reduce the bacterium's ability to form biofilms and adhere to biotic surfaces.

Background: "Smart'" polymers with reversible responsiveness to temperature stimuli are among the most promising carriers for controlled drug delivery, as temperature is a critical physiological factor within the human body. The majority of studies on the coupling of polymers with active substances have employed the method of attaching the drug to the polymer after its synthesis. The direct addition of the drug during the polymerization process has not been attempted, primarily due to concerns about the potential degradation of the active substance under harsh reaction conditions, such as elevated temperature and the presence of free radicals.

Objectives: This study aimed to evaluate the stability of a selected model drug - naproxen sodium (NAP), under extreme synthesis conditions, thereby providing insights into its resilience in such an environment.

Material and methods: The Thermo Scientific Dionex UltiMate 3000 system was utilized for the chromatographic analyses. The separations were carried out on a Phenomenex Kinetex 2.6 µm, C18 100A, 150 × 2.1 mm column at 30°C. A high-performance liquid chromatography (HPLC) assay was carried out using gradient elution with a flow rate 0.4 mL/min and mobile phase of water 0.1% formic acid (A) and acetonitrile 0.1% formic acid (B) with the detector set at the wavelength of 254 nm.

Results: Chromatographic analysis showed new peaks indicating decomposition on NAP in ambient temperature in the presence of 2.2'-azobis(2-methylpropionamidine) dihydrochloride (AIBA).

Conclusion: Our findings indicate that NAP cannot be combined with the polymer during the polymerization process in extreme conditions of synthesis, specifically at temperatures of 70°C and in the presence of radicals, without undergoing decomposition. Nevertheless, further trials and tests are necessary to substantiate this hypothesis. One potential avenue for further investigation would be trials with alternative radical initiators, such as potassium persulfate (KPS).

Background: Polyethylene glycols (PEGs) are widely applied in technology of pharmaceutical products, as well as in other branches of industry. Owing to their physicochemical properties, they are particularly effective in enhancing the solubility of a wide range of drug formulations.

Objectives: The aim of the study was to evaluate the effect of PEGs on the physicochemical parameters of model systems containing different concentrations of sodium chloride (NaCl), with particular emphasis on the specific conductivity of these solutions.

Material and methods: A series of aqueous solutions containing 0.9% and 9.0% NaCl, with increasing mass concentrations (2.0-25.0% w/w) of PEG 200 and PEG 4000, were prepared and analyzed. Their specific conductivity was tested using a CC-505 conductivity meter with an EC-70 conductivity sensor; also, densities and viscosities of the tested solutions were evaluated.

Results: The increased concentration of polymers in the system resulted in decrease of the specific conductivity and molar conductivity in each of the series of evaluated solutions. An inverse relationship occurred in viscosity measurements, which increased with increasing PEG content in the system.

Conclusions: The addition of PEG 200 and PEG 4000 to aqueous NaCl solutions affected both the specific conductivity and viscosity of these systems. Both types of polymers had similar effects on conductivity changes in 0.9% and 9.0% NaCl solutions.

Several factors, including characteristic polymer composition of the cell wall, based on peptidoglycans cross-linked with arabinogalactans, together with the lipid layer contribute to the high resistance of Mycobacterium tuberculosis to antibiotics and other anti-tuberculosis drugs, leading to the development of new treatment methods. Implementation of therapeutic drug monitoring for anti-mycobacterial drugs in routine clinical practice requires understanding of the limited stability of these drugs. Rifampicin and isoniazid are the main anti-tuberculosis drugs that generate degradation products during sample handling and storage. Therefore, analytical methods used for analysis of clinical samples collected from tuberculosis patients treated with a combination of different drugs should enable the separation of the studied analytes from their metabolites and degradation products. Moreover, the samples require strictly regulated collection and storage conditions to prevent degradation processes. The purpose of this review was to present recent data on the stability studies of anti-mycobacterial drugs, specifically used as first-line treatment in patients with tuberculosis. Detailed degradation pathway of rifampicin was described, including conditions influencing the formation of specific rifampicin related substances. Moreover, the results of the stability studies of anti-mycobacterial drugs were presented in various matrices in conditions determined by international guidance such as U.S. Food and Drug Administration (FDA) or International Council for Harmonisation (ICH) guidelines. Particular attention was given to analytical methods designed for analysis of anti-mycobacterial drugs in the presence of their degradation products. Finally, recommendations proposed by different authors for collection, processing and storage of clinical samples to increase stability of anti-mycobacterial drugs were summarized.

Background: Poly(glycerol sebacate) is a polymeric material with potential biomedical application in the field of tissue engineering. In order to act as a biodegradable scaffold, its incubation study is vital to simulate its behavior.

Objectives: This study explores the degradation of porous poly(glycerol sebacate)/hydroxyapatite scaffolds subjected to incubation in various physiological solutions.

Material and methods: The research involved monitoring pH and conductivity values over a 14-day period, as well as analyzing the swelling capacity and mass alterations of the scaffolds.

Results: In simulated body fluid (SBF) and phosphate-buffered saline (PBS), the pH levels remained relatively stable, whereas Ringer's solution caused a pH decrease. Conversely, artificial saliva demonstrated an increase in pH, and distilled water caused a slight decrease. The conductivity values remained stable in SBF and Ringer's solution, slightly decreased in PBS, increased in artificial saliva, and significantly increased in distilled water. The swelling capacity of the scaffolds varied depending on the solution used, with the lowest equilibrium swelling observed in SBF and PBS. The effect of the presence of ceramics on this parameter was also observed. The mass changes of the scaffolds indicated deposition of particles or salts from the incubation solutions, and subsequent rinsing in distilled water led to a decrease in mass. Scanning electron microscopy (SEM) imaging and elemental analysis confirmed the presence of crystallized salts on the scaffold surfaces after incubation in SBF. Surface roughness measurements revealed changes in roughness depending on the solution, with deposition of additional layers in SBF and degradation in artificial saliva.

Conclusions: In summary, the scaffolds exhibited biodegradation in physiological solutions, with variations in pH, conductivity, swelling capacity, mass changes, and surface morphology depending on the specific solution and scaffold composition.

The spinal cord is one of the most important part of the human nervous system and great importance is placed on developing the best treatment for its damage. 3D bio-printing technology, and the fabrication of special scaffolds using it, is a potential solution for regenerating damage in spinal cord injuries (SCIs). Bio-printing can be divided into indirect and direct bio-printing, while among the bio-printing methods, inkjet bio-printing, fused deposition modeling (FDM), extrusion bio-printing, or light-assisted bio-printing can be distinguished. The last group can be in turn divided into several separate techniques such as digital light processing (DLP), stereolithography (SLA) and laser-assisted bio-printing (LAB). While bio-printing technology for the treatment of SCI is in the early stages of research, several successful trials have already been performed, where the use of such scaffolds has resulted in at least partial restoration of autonomic nervous system function in patients with chronic and acute SCI.

Background: The drug interactions with the lipid membranes are crucial in many biochemical processes. Phospholipid model membranes are often used to assess such interactions. Our team has been researching new compounds with anti-inflammatory and analgesic effects for many years. Such compounds are derivatives of the well-known non-steroidal anti-inflammatory drug (NSAID) - meloxicam (MLX). Their biological target is cyclooxygenase (COX) - a membrane protein. The NSAIDs are mainly taken orally; therefore, drug-membrane interaction is a preliminary stage in the body.

Objectives: The purpose of the present work was to investigate the ability of 2 new MLX derivatives (compound PR51 and PR52) to interact with model membranes, in comparison to known NSAIDs medicine - MLX. The differential scanning calorimetry (DSC) method was used to study those interactions. As a model membrane, bilayers obtained from a phospholipid (1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC)) were used.

Material and methods: Calorimetric measurements were performed using a differential scanning calorimeter DSC 214 Polyma equipped with an intracooler IC70.

Results: All examined compounds decreased the main transition temperature of DPPC in a concentration-dependent manner. The addition of studied compounds to DPPC also resulted in broadening of the transition peaks. Moreover, all examined compounds decreased the enthalpy of the DPPC main phase transition. For all DPPC gel-liquid crystalline phase transition parameters, the most pronounced effects were found for PR51 compound.

Conclusion: We have shown that the above interactions depend on the chemical structure of individual compound. All studied compounds alter biophysical properties of phospholipid bilayer.