Sublingual drug delivery allows systemic delivery of drug without difficulties connected with the gastrointestinal pathway. We developed a new simple protocol for easy-to-use processing and storage of porcine sublingual mucosal membrane for in vitro studies using "flash freezing" in liquid nitrogen. All the dextrans used as mucosal membrane integrity and permeability markers permeated only slowly through sublingual mucosa illustrating usability both the "fresh" and "flash frozen" sublingual membranes whereas conventional cold storage "frozen" membranes have shown significantly higher permeabilities for macromolecules due to the sustained damage. The permeability values were too low to expect dextrans to be potential carriers at this context. To test albumin as a drug carrier we compared FITC-albumin permeation from solutions vs. nanofiber mats donors. To increase the amounts and prolong the transport, we manufactured nanofiber mats loaded with fluorescently marked albumin using well-scalable electrospinning technology. Nanofiber mats have allowed albumin passage through the sublingual membrane in similar amounts as from the pure artificial saliva solution. Since salivary washout strictly limits the duration of liquid dosages, nanofiber mats may thus permit prolonged sublingual administration.
- MeSH
- albuminy aplikace a dávkování MeSH
- aplikace sublinguální MeSH
- dextrany aplikace a dávkování MeSH
- fluorescein-5-isothiokyanát aplikace a dávkování analogy a deriváty MeSH
- kofein aplikace a dávkování MeSH
- nanovlákna aplikace a dávkování MeSH
- permeabilita MeSH
- prasata MeSH
- roztoky MeSH
- sliznice anatomie a histologie metabolismus MeSH
- systémy cílené aplikace léků * MeSH
- zmrazování MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Currently, chemotherapy is the most common treatment for oncological diseases. Systemic administration of chemotherapeutics provides an easy and effective distribution of the active agents throughout the patient's body, however organs may be severely impaired by serious life-threatening side effects. In many oncological diseases, particularly solid tumors, the local application of chemotherapeutics would be advantageous. Recently, nanofibrous materials as local drug delivery systems have attracted much attention. They have considerable potential in the treatment of various cancers as they can provide a high concentration of the drug at the target site for a prolonged time, thereby lowering total exposure and adverse effects. The present review describes the specifics of drug delivery to the tumor microenvironment, basic characteristics of nanofibrous materials and their preparation, and comprehensively summarizes recent scientific reports concerning in vivo experiments with drug-loaded electrospun nanofibrous systems designed for local anticancer therapy.
A nanofibrous membrane carrier for nearly water insoluble drug diosmin was formulated. The aim of this study was to evaluate the drug release and dissolution properties in an aqueous buffer of pH 7.8, and to compare the suitability of the drug carrier with the available drug forms and screen diosmin absorption extent. The membranes were produced from HPC/PVA/PEO-drug water solutions and then evaluated by SEM and DSC measurements. The results showed that diosmin was incorporated within the nanofibers in an amorphous state, and/or as a solid dispersion. The results of in vitro release experiments excerpt a very fast release of the drug, followed by the formation of an over saturated solution and partial precipitation of the drug (a "spring" effect). The enormous increases in dissolution of the drug from a nanofibrous carrier, compared to a micronized and crystalline form, was achieved. The in vivo bioavailability study carried out on rats showed higher initial drug plasma levels and higher AUC values after administration of the nanofibrous drug formulation, compared to the micronized form. The results of the study demonstrated that the improvement of the diosmin in vitro dissolution also brought the enhanced in vivo absorption extent of the drug.
- MeSH
- aplikace orální MeSH
- diosmin aplikace a dávkování krev chemie farmakokinetika MeSH
- intestinální absorpce MeSH
- nanovlákna aplikace a dávkování chemie MeSH
- nosiče léků aplikace a dávkování chemie farmakokinetika MeSH
- potkani Wistar MeSH
- příprava léků metody MeSH
- rozpustnost MeSH
- roztoky MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of the study was to evaluate the effect of a cell-free hyaluronate/type I collagen/fibrin composite scaffold containing polyvinyl alcohol (PVA) nanofibers enriched with liposomes, basic fibroblast growth factor (bFGF) and insulin on the regeneration of osteochondral defects. A novel drug delivery system was developed on the basis of the intake effect of liposomes encapsulated in PVA nanofibers. Time-controlled release of insulin and bFGF improved MSC viability in vitro. Nanofibers functionalized with liposomes also improved the mechanical characteristics of the composite gel scaffold. In addition, time-controlled release of insulin and bFGF stimulated MSC recruitment from bone marrow in vivo. Cell-free composite scaffolds containing PVA nanofibers enriched with liposomes, bFGF, and insulin were implanted into seven osteochondral defects of miniature pigs. Control defects were left untreated. After 12 weeks, the composite scaffold had enhanced osteochondral regeneration towards hyaline cartilage and/or fibrocartilage compared with untreated defects that were filled predominantly with fibrous tissue. The cell-free composite scaffold containing PVA nanofibers, liposomes and growth factors enhanced migration of the cells into the defect, and their differentiation into chondrocytes; the scaffold was able to enhance the regeneration of osteochondral defects in minipigs.
- MeSH
- buněčná diferenciace MeSH
- buňky kostní dřeně cytologie MeSH
- chondrocyty cytologie MeSH
- fibrin chemie MeSH
- fibroblastový růstový faktor 2 aplikace a dávkování MeSH
- inzulin aplikace a dávkování MeSH
- kolagen typu I chemie MeSH
- kyselina hyaluronová chemie MeSH
- liposomy MeSH
- mezenchymální kmenové buňky cytologie MeSH
- miniaturní prasata MeSH
- modul pružnosti MeSH
- nanovlákna aplikace a dávkování chemie MeSH
- polyvinylalkohol chemie MeSH
- prasata MeSH
- regenerace kostí * MeSH
- tkáňové podpůrné struktury MeSH
- viabilita buněk MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Titanium dioxide nanofibres (TiO2) were intratracheally instilled in dose of 4 mg/0.2 mL saline solution per animal (Wistar rats). After 48 hours and 14 days the animals were exsanguinated (under i.p. thiopental narcosis), bronchoalveolar lavage (BAL) was perfomed and cells from BAL fluid were isolated. Following inflammatory, cytotoxic and oxidative stress BAL parameters were examined: differential cell count (% of alveolar macrophages (AM), polymorphonuclears and lymphocytes); the viability and phagocytic activity of AM; the proportion of immature cells; the proportion of multinucleated cells; count of AM/mL lavage; count of BAL cells/mL lavage; the level of ascorbic acid and activity of superoxide dismutase, both in tissue homogenate and in bronchoalveolar lavage fluid. The majority of examined BAL parameters in the acute and subacute phase in our study suggest serious inflammatory and cytotoxic processes in lung after exposure to TiO2.
- MeSH
- alveolární makrofágy imunologie MeSH
- bronchoalveolární lavážní tekutina cytologie MeSH
- krysa rodu rattus MeSH
- leukocyty imunologie MeSH
- mediátory zánětu imunologie MeSH
- nanovlákna aplikace a dávkování škodlivé účinky MeSH
- oxidační stres imunologie MeSH
- potkani Wistar MeSH
- titan aplikace a dávkování škodlivé účinky imunologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Micro-dispersed oxidized cellulose, already used for hemostasis, might be helpful for introduction of an antimicrobial drug. AIM: To examine the effect of topically applied gentamicin attached to a new biodegradable carrier formed by micro-dispersed oxidized cellulose in microfiber and nanofiber form for treatment of acute wound infection and to assess the influence of this carrier on healing. MATERIALS AND METHODS: A model of a full-thickness infected dermal wound was created in 12 female domestic pigs. The effectiveness of topical gentamicin delivered with micro-dispersed oxidized cellulose carrier was tested in acute wound infections caused by Staphylococcus aureus, Pseudomonas aeruginosa, or Escherichia coli. RESULTS: The effectiveness of nanofiber micro-dispersed oxidized cellulose with gentamicin was proved according to culture findings. When assessed macroscopically, 100% of wounds treated by the nanofiber product had no signs of local infection. When microfiber micro-dispersed oxidized cellulose was used, cultures demonstrated residual bacteria in 94.4% of treated incisions despite the absence of clinically recognized infection. CONCLUSIONS: Micro-dispersed oxidized cellulose carrier with a sufficient concentration of an attached antibiotic appears to be effective for the treatment of full-thickness skin infections. The positive influence of the product on the healing of a dermal incision was shown, and a good hemostatic effect was confirmed.
- MeSH
- antiinfekční látky lokální terapeutické užití MeSH
- aplikace lokální MeSH
- bakteriální infekce farmakoterapie MeSH
- celulosa oxidovaná aplikace a dávkování MeSH
- Escherichia coli účinky léků izolace a purifikace MeSH
- gentamiciny terapeutické užití MeSH
- hojení ran MeSH
- infekce v ráně farmakoterapie MeSH
- modely nemocí na zvířatech MeSH
- nanovlákna aplikace a dávkování MeSH
- nosiče léků aplikace a dávkování MeSH
- prasata MeSH
- Pseudomonas aeruginosa účinky léků izolace a purifikace MeSH
- Staphylococcus aureus účinky léků izolace a purifikace MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
