Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.

• MeSH
• akrylové pryskyřice * chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• difrakce rentgenového záření MeSH
• hydrogely * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• králíci MeSH
• lékové transportní systémy MeSH
• léky s prodlouženým účinkem chemie   farmakokinetika   MeSH
• mikroskopie elektronová rastrovací MeSH
• nosiče léků chemie   MeSH
• poloxamer * chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• termogravimetrie MeSH
• timolol * aplikace a dávkování   farmakokinetika   chemie   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.

• MeSH
• akrylamidy chemie   farmakologie   aplikace a dávkování   MeSH
• antiflogistika farmakologie   aplikace a dávkování   chemie   MeSH
• Aspirin * aplikace a dávkování   farmakologie   chemie   MeSH
• cyklooxygenasy metabolismus   MeSH
• inhibitory cyklooxygenasy farmakologie   aplikace a dávkování   chemie   MeSH
• léky s prodlouženým účinkem * MeSH
• mediátory zánětu metabolismus   MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• polymery * chemie   aplikace a dávkování   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Dental hypersensitivity remains widespread, underscoring the need for materials that can effectively seal dental tubules. This study evaluated the potential of bioactive-glass-infused hydroxyethyl cellulose gels in this context. METHODS: Five gels were synthesized, each containing 20% bioactive glass (specifically, 45S5, S53P4, Biomin F, and Biomin C), with an additional blank gel serving as a control. Subjected to two months of accelerated aging at 37 ± 2 °C, these gels were assessed for key properties: viscosity, water disintegration time, pH level, consistency, adhesion to glass, and element release capability. RESULTS: Across the board, the gels facilitated the release of calcium, phosphate, and silicon ions, raising the pH from 9.00 ± 0.10 to 9.7 ± 0.0-a range conducive to remineralization. Dissolution in water occurred within 30-50 min post-application. Viscosity readings showed variability, with 45S5 reaching 6337 ± 24 mPa/s and Biomin F at 3269 ± 18 mPa/s after two months. Initial adhesion for the blank gel was measured at 0.27 ± 0.04 Pa, increasing to 0.73 ± 0.06 Pa for the others over time. Gels can release elements upon contact with water (Ca- Biomin C 104.8 ± 15.7 mg/L; Na- Biomin F 76.30 ± 11.44 mg/L; P- Biomin C 2.623 ± 0.393 mg/L; Si- 45S5-45.15 ± 6.77mg/L, F- Biomin F- 3.256 ± 0.651mg/L; Cl- Biomin C 135.5 ± 20.3 mg/L after 45 min). CONCLUSIONS: These findings highlight the gels' capacity to kickstart the remineralization process by delivering critical ions needed for enamel layer reconstruction. Further exploration in more dynamic, real-world conditions is recommended to fully ascertain their practical utility.

• Publikační typ
• časopisecké články MeSH

A film-forming system (FFS) represents a convenient topical dosage form for drug delivery. In this study, a non-commercial poly(lactic-co-glycolic acid) (PLGA) was chosen to formulate an FFS containing salicylic acid (SA) and methyl salicylate (MS). This unique combination is advantageous from a therapeutic point of view, as it enabled modified salicylate release. It is beneficial from a technological perspective too, because it improved thermal, rheological, and adhesive properties of the in situ film. DSC revealed complete dissolution of SA and good miscibility of MS with the polymer. MS also ensures optimal viscoelastic and adhesive properties of the film, leading to prolonged and sustained drug release. The hydrolysis of MS to active SA was very slow at skin pH 5.5, but it apparently occurred at physiological pH 7.4. The film structure is homogeneous without cracks, unlike some commercial preparations. The dissolution study of salicylates revealed different courses in their release and the influence of MS concentration in the film. The formulated PLGA-based FFS containing 5 % SA and 10 % MS is promising for sustained and prolonged local delivery of salicylates, used mainly for keratolytic and anti-inflammatory actions and pain relief.

• MeSH
• aplikace kožní MeSH
• aplikace lokální MeSH
• farmaceutická chemie metody   MeSH
• koncentrace vodíkových iontů MeSH
• kopolymer kyseliny glykolové a mléčné * chemie   MeSH
• kůže metabolismus   MeSH
• kyselina mléčná * chemie   MeSH
• kyselina polyglykolová * chemie   MeSH
• kyselina salicylová * aplikace a dávkování   chemie   farmakokinetika   MeSH
• lékové transportní systémy * metody   MeSH
• léky s prodlouženým účinkem MeSH
• rozpustnost MeSH
• salicylany * aplikace a dávkování   chemie   farmakokinetika   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH

The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself.

• MeSH
• antiflogistika terapeutické užití   MeSH
• dexamethason MeSH
• doxorubicin chemie   MeSH
• leukocyty mononukleární * MeSH
• lidé MeSH
• myši MeSH
• nanomedicína MeSH
• nosiče léků chemie   MeSH
• polymery chemie   MeSH
• revmatické nemoci * MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Background and Objectives: The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Materials and Methods: Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. Results: The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for Cmax, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC0-t, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC0-∞. Conclusions: Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed.

• MeSH
• klinické křížové studie MeSH
• lidé MeSH
• omeprazol * chemie   MeSH
• terapeutická ekvivalence MeSH
• tobolky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

The colonisation of the surface of removable acrylic dentures by various types of microorganisms can lead to the development of various diseases. Therefore, the creation of a bioactive material is highly desirable. This study aimed to develop a denture base material designed to release bioactive ions into the oral environment during use. Four types of bioactive glasses (BAG)-S53P4, Biomin F, 45S5, and Biomin C-were incorporated into the PMMA acrylic resin, with each type constituting 20 wt.% (10 wt.% non-silanised and 10% silanised) of the mixture, while PMMA acrylic resin served as the control group. The specimens were subsequently immersed in distilled water, and pH measurements of the aqueous solutions were taken every seven days for a total of 38 days. Additionally, surface roughness and translucency measurements were recorded both after preparation and following seven days of immersion in distilled water. The cytotoxicity of these materials on human fibroblast cells was evaluated after 24 and 48 h using Direct Contact and MTT assays. Ultimately, the elemental composition of the specimens was determined through energy-dispersive X-ray (EDX) spectroscopy. In general, the pH levels of water solutions containing BAG-containing acrylics gradually increased over the storage period, reaching peak values after 10 days. Notably, S53P4 glass exhibited the most significant increase, with pH levels rising from 5.5 to 7.54. Surface roughness exhibited minimal changes upon immersion in distilled water, while a slight decrease in material translucency was observed, except for Biomin C. However, significant differences in surface roughness and translucency were observed among some of the BAG-embedded specimens under both dry and wet conditions. The composition of elements declared by the glass manufacturer was confirmed by EDX analysis. Importantly, cytotoxicity analysis revealed that specimens containing BAGs, when released into the environment, did not adversely affect the growth of human gingival fibroblast cells after 48 h of exposure. This suggests that PMMA acrylics fabricated with BAGs have the potential to release ions into the environment and can be considered biocompatible materials. Further clinical trials are warranted to explore the practical applications of these materials as denture base materials.

• Publikační typ
• časopisecké články MeSH

Predložená práca sa zaoberá vývojom matricovej tablety s predĺženým uvoľňovaním ľahko rozpustného liečiva pramipexolu. Ako polymér riadiaci uvoľňovanie liečiva z vybraných prototypov bol použitý nový excipient Kollidon SR (zmes 80 % polyvinylacetátu a 20 % polyvinylpyrolidónu) a hypromelóza K15M. Testovali sa rôzne koncentrácie polymérov s cieľom dosiahnúť stabilné a pH nezávislé uvoľňovanie pramipexolu 0,26 mg po dobu 24 hodín, vzorky boli pripravené vlhkou granuláciou a lisovaním matricových tabliet. Uvoľňovanie liečiva bolo sledované v disolučných médiách s hodnotami pH od 1,2 až po 6,8 a porovnávané s referenčným prípravkom na báze hydrofilnej matrice s kombináciu troch rôznych polymérov. Požadovaný liberačný profil nízkodávkového liečiva bol dosiahnutý použitím 60,0 hm.% Kollidonu SR vo všetkých médiách a vybraná formulácia F2 vykazovala dostatočnú odolnosť aj voči pôsobeniu etanolu až do koncentrácie 40 obj.%.

The present work deals with the development of a prolonged release matrix tablet of the readily soluble drug pramipexole. The new excipient Kollidon SR (a mix-ture of 80% polyvinyl acetate and 20% polyvinylpyrroli-done) and hypromellose K15M were used as polymers to control drug release from selected prototypes. Various polymer concentrations were tested to achieve a stable and pH independent release of pramipexole of 0.26 mg over 24 hours; samples were prepared by wet granulation and compression of matrix tablets. Drug release was moni-tored in dissolution media with pH values from 1.2 to 6.8 and compared with a reference product based on a hydro-philic matrix with a combination of three different poly-mers. The required release profile of the low-dose drug formulation was achieved using 60.0% (w/w) of Kollidon SR in all dissolution media and the selected formulation F2 demonstrated a sufficient alcohol resistance up to the ethanol concentration of 40% (v/v).

• MeSH
• aplikace orální MeSH
• léky s prodlouženým účinkem aplikace a dávkování   farmakokinetika   MeSH
• lidé MeSH
• Parkinsonova nemoc farmakoterapie   MeSH
• polymery MeSH
• pramipexol * aplikace a dávkování   farmakokinetika   MeSH
• tablety MeSH
• uvolňování léčiv MeSH
• vyvíjení léků * MeSH
• Check Tag
• lidé MeSH

Chemotherapy is the most prominent route in cancer therapy for prolonging the lifespan of cancer patients. However, its non-target specificity and the resulting off-target cytotoxicities have been reported. Recent in vitro and in vivo studies using magnetic nanocomposites (MNCs) for magnetothermal chemotherapy may potentially improve the therapeutic outcome by increasing the target selectivity. In this review, magnetic hyperthermia therapy and magnetic targeting using drug-loaded MNCs are revisited, focusing on magnetism, the fabrication and structures of magnetic nanoparticles, surface modifications, biocompatible coating, shape, size, and other important physicochemical properties of MNCs, along with the parameters of the hyperthermia therapy and external magnetic field. Due to the limited drug-loading capacity and low biocompatibility, the use of magnetic nanoparticles (MNPs) as drug delivery system has lost traction. In contrast, MNCs show higher biocompatibility, multifunctional physicochemical properties, high drug encapsulation, and multi-stages of controlled release for localized synergistic chemo-thermotherapy. Further, combining various forms of magnetic cores and pH-sensitive coating agents can generate a more robust pH, magneto, and thermo-responsive drug delivery system. Thus, MNCs are ideal candidate as smart and remotely guided drug delivery system due to a) their magneto effects and guide-ability by the external magnetic fields, b) on-demand drug release performance, and c) thermo-chemosensitization under an applied alternating magnetic field where the tumor is selectively incinerated without harming surrounding non-tumor tissues. Given the important effects of synthesis methods, surface modifications, and coating of MNCs on their anticancer properties, we reviewed the most recent studies on magnetic hyperthermia, targeted drug delivery systems in cancer therapy, and magnetothermal chemotherapy to provide insights on the current development of MNC-based anticancer nanocarrier.

• MeSH
• indukovaná hypertermie * metody   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• magnetické pole MeSH
• magnetismus MeSH
• nádory * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Nano-sized carriers are widely studied as suitable candidates for the advanced delivery of various bioactive molecules such as drugs and diagnostics. Herein, the development of long-circulating stimuli-responsive polymer nanoprobes tailored for the fluorescently-guided surgery of solid tumors is reported. Nanoprobes are designed as long-circulating nanosystems preferably accumulated in solid tumors due to the Enhanced permeability and retention effect, so they act as a tumor microenvironment-sensitive activatable diagnostic. This study designs polymer probes differing in the structure of the spacer between the polymer carrier and Cy7 by employing pH-sensitive spacers, oligopeptide spacers susceptible to cathepsin B-catalyzed enzymatic hydrolysis, and non-degradable control spacer. Increased accumulation of the nanoprobes in the tumor tissue coupled with stimuli-sensitive release behavior and subsequent activation of the fluorescent signal upon dye release facilitated favorable tumor-to-background ratio, a key feature for fluorescence-guided surgery. The probes show excellent diagnostic potential for the surgical removal of intraperitoneal metastasis and orthotopic head and neck tumors with very high efficacy and accuracy. In addition, the combination of macroscopic resection followed by fluorescence-guided surgery using developed probes enable the identification and resection of most of the CAL33 intraperitoneal metastases with total tumor burden reduced to 97.2%.

• MeSH
• chytré polymery * MeSH
• fluorescence MeSH
• fluorescenční barviva chemie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí MeSH
• nádory hlavy a krku * diagnostické zobrazování   chirurgie   MeSH
• polymery MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH