Although progress is evident in the effective treatment of joint replacement-related infections, it still remains a serious issue in orthopedics. As an example, the local application of antibiotics-impregnated bone grafts supplies the high drug levels without systemic side effects. However, antibiotics in the powder or solution form could be a risk for local toxicity and do not allow sustained drug release. The present study evaluated the use of an antibiotic gel, a water-in-oil emulsion, and a PLGA microparticulate solid dispersion as depot delivery systems impregnating bone grafts for the treatment of joint replacement-related infections. The results of rheological and bioadhesive tests revealed the suitability of these formulations for the impregnation of bone grafts. Moreover, no negative effect on proliferation and viability of bone marrow mesenchymal stem cells was detected. An ex vivo dissolution test of vancomycin hydrochloride and gentamicin sulphate from the impregnated bone grafts showed a reduced burst and prolonged drug release. The PLGA-based formulation proved to be particularly promising, as one-day burst release drugs was only 15% followed with sustained antibiotics release with zero-order kinetics. The results of this study will be the basis for the development of a new product in the Tissue Section of the University Hospital for the treatment of bone defects and infections of joint replacements.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• artroplastiky kloubů * MeSH
• emulze MeSH
• gentamiciny MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• prášky, zásypy, pudry MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• vankomycin MeSH
• voda MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

As proven in clinical trials, superficial fungal infections can be effectively treated by single topical application of terbinafine hydrochloride (Ter-HCl) in a film forming system (FFS). Poly(lactic-co-glycolic acid) (PLGA) derivatives, originally synthesized with intention to get carriers with optimized properties for drug delivery, and multifunctional plasticizers - ethyl pyruvate, methyl salicylate, or triacetin - were used for formulation of Ter-HCl loaded FFSs. After spraying, a biodegradable, transparent, adhesive, and occlusive thin layer is formed on the skin, representing drug depot. In situ formed films were characterized by thermal, structural, viscoelastic, and antifungal properties as well as drug release and skin penetration. DSC and SEM showed fully amorphous films with Ter-HCl dissolved in PLGA in high concentration (up to 15%). FFSs are viscoelastic fluids with viscosity which can be easily adjusted by the type of plasticizer used and its concentration. The formulations showed excellent bioadhesion properties, thus ensuring persistence on the skin. In situ film based on branched PLGA/A plasticized with 10% of ethyl pyruvate allowed prolonged release of Ter-HCl by linear kinetics for the first 6 days with a total time of almost 14 days. During ex vivo human skin penetration experiment, Ter-HCl was found to be located only in its target layer, the epidermis. According to our results, plasticized branched PLGA derivatives loaded by Ter-HCl are suitable for the development of FFSs for superficial fungal infections treatment.

• MeSH
• antifungální látky MeSH
• lidé MeSH
• mykózy * MeSH
• nosiče léků * MeSH
• terbinafin MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Infectious stomatitis represents the most common oral cavity ailments. Current therapy is insufficiently effective because of the short residence time of topical liquid or semisolid medical formulations. An innovative application form based on bioadhesive polymers featuring prolonged residence time on the oral mucosa may be a solution to this challenge. This formulation consists of a mucoadhesive oral film with incorporated nanocomposite biomaterial that is able to release the drug directly at the target area. This study describes the unique approach of preparing mucoadhesive oral films from carmellose with incorporating a nanotechnologically modified clay mineral intercalated with chlorhexidine. The multivariate data analysis was employed to evaluate the influence of the formulation and process variables on the properties of the medical preparation. This evaluation was complemented by testing the antimicrobial and antimycotic activity of prepared films with the aim of finding the most suitable composition for clinical application. Generally, the best results were obtained with sample containing 20 mg of chlorhexidine diacetate carried by vermiculite, with carmellose in the form of nonwoven textile in its structure. In addition to its promising physicomechanical, chemical, and mucoadhesive properties, the formulation inhibited the growth of Staphylococcus and Candida; the effect was prolonged for tens of hours.

• MeSH
• antiinfekční látky aplikace a dávkování   chemie   MeSH
• biokompatibilní materiály aplikace a dávkování   chemie   MeSH
• chitosan chemie   MeSH
• chlorhexidin aplikace a dávkování   chemie   MeSH
• farmaceutická chemie MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• nanokompozity aplikace a dávkování   chemie   MeSH
• polymery aplikace a dávkování   chemie   MeSH
• sodná sůl karboxymethylcelulosy aplikace a dávkování   chemie   MeSH
• stomatitida farmakoterapie   mikrobiologie   MeSH
• ústa účinky léků   mikrobiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Topical delivery of 5-aminosalicylic acid (5-ASA) to the colonic mucosa is important in order to achieve effective drug concentration in the site of inflammation and to minimize its systemic availability. 5-ASA loaded pellets were prepared by an extrusion/spheronization method. Mucoadhesive biopolymer chitosan was incorporated into the pellets, and drug delivery to the colon was controlled by the pH-sensitive polymer Eudragit® FS. Dissolution profiles of coated pellets revealed no drug release at pH 1.2 within 2h and release as intended in the simulated distal ileum and colon. In vivo, chitosan-core drug loaded pellets (AMCh) showed 2.5-fold higher drug metabolite concentration than after chitosan free pellets (AM) administration in the inflamed colonic tissue. Additionally, AMCh demonstrated decreased in AUC in colitis group (1507 ± 400 ng h/ml) compared with AM (1907 ± 122 ng h/ml). In terms of therapeutic efficiency, administration of pellets markedly decreased the colon/body weight ratio (colitis: 0.0355 ± 0.0028; AM 0.0092 ± 0.0033; AMCh 0.0086 ± 0.0022) and myeloperoxidase activity (colitis: 3212 ± 294 U/g tissue; AM 796 ± 211 U/g; AMCh 552 ± 319 U/g). Bioadhesive chitosan pellets showed additional beneficial properties for colonic 5-ASA delivery in the treatment of inflammatory bowel disease by increasing the drug concentration locally.

• MeSH
• antiflogistika aplikace a dávkování   chemie   MeSH
• biopolymery aplikace a dávkování   chemie   farmakokinetika   MeSH
• chitosan aplikace a dávkování   chemie   farmakokinetika   MeSH
• implantované léky aplikace a dávkování   chemie   farmakokinetika   MeSH
• kolitida farmakoterapie   metabolismus   MeSH
• kolon účinky léků   metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• krysa rodu rattus MeSH
• lékové transportní systémy metody   MeSH
• mesalamin aplikace a dávkování   chemie   farmakokinetika   MeSH
• peroxidasa metabolismus   MeSH
• potkani Wistar MeSH
• rozpustnost MeSH
• velikost částic MeSH
• zánět farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• fyzikální chemie MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Fyzikální chemie
• NLK Obory
• chemie, klinická chemie

Modifications of poly(2-hydroxyethyl methacrylate) (PHEMA) with cholesterol and the introduction of large pores have been developed to create highly superporous hydrogels that promote cell-surface interactions and that can serve as a permissive scaffold for spinal cord injury (SCI) treatment. Highly superporous cholesterol-modified PHEMA scaffolds have been prepared by the bulk radical copolymerization of 2-hydroxyethyl methacrylate (HEMA), cholesterol methacrylate (CHLMA), and ethylene dimethacrylate (EDMA) cross-linking agent in the presence of ammonium oxalate crystals to establish interconnected pores in the scaffold. Moreover, 2-[(methoxycarbonyl)methoxy]ethyl methacrylate (MCMEMA) was incorporated in the polymerization recipe and hydrolyzed, thus introducing carboxyl groups in the hydrogel to control its swelling and softness. The hydrogels supported the in vitro adhesion and proliferation of rat mesenchymal stem cells. In an in vivo study of acute rat SCI, hydrogels were implanted to bridge a hemisection cavity. Histological evaluation was done 4 weeks after implantation and revealed the good incorporation of the implanted hydrogels into the surrounding tissue, the progressive infiltration of connective tissue and the ingrowth of neurofilaments, Schwann cells, and blood vessels into the hydrogel pores. The results show that highly superporous cholesterol-modified PHEMA hydrogels have bioadhesive properties and are able to bridge a spinal cord lesion.

• MeSH
• biokompatibilní materiály chemie   MeSH
• buněčná adheze MeSH
• cholesterol chemie   MeSH
• experimentální implantáty MeSH
• hydrogely chemie   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• mechanický stres MeSH
• methakryláty chemie   MeSH
• mezenchymální kmenové buňky cytologie   fyziologie   MeSH
• molekulární struktura MeSH
• polyhydroxyethylmethakrylát chemie   MeSH
• poranění míchy patologie   MeSH
• poréznost MeSH
• potkani Wistar MeSH
• proliferace buněk MeSH
• regenerace míchy MeSH
• regenerace nervu MeSH
• testování materiálů MeSH
• tkáňové podpůrné struktury chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

The opportunistic pathogen Burkholderia cenocepacia expresses several soluble lectins, among them BC2L-C. This lectin exhibits two domains: a C-terminal domain with high sequence similarity to the recently described calcium-dependent mannose-binding lectin BC2L-A, and an N-terminal domain of 156 amino acids without similarity to any known protein. The recombinant N-terminal BC2L-C domain is a new lectin with specificity for fucosylated human histo-blood group epitopes H-type 1, Lewis b, and Lewis Y, as determined by glycan array and isothermal titration calorimetry. Methylselenofucoside was used as ligand to solve the crystal structure of the N-terminal BC2L-C domain. Additional molecular modeling studies rationalized the preference for Lewis epitopes. The structure reveals a trimeric jellyroll arrangement with striking similarity to TNF-like proteins, and to BclA, the spore protein from Bacillus anthracis which may play an important role in bioadhesion of anthrax spores in human lungs.

• MeSH
• antigeny krevních skupin chemie   imunologie   metabolismus   MeSH
• bakteriální proteiny chemie   metabolismus   MeSH
• Burkholderia chemie   metabolismus   MeSH
• epitopy chemie   imunologie   metabolismus   MeSH
• fukosa chemie   metabolismus   MeSH
• kvarterní struktura proteinů MeSH
• lektiny chemie   metabolismus   MeSH
• lidé MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Ciele štúdie: Autor analyzuje výsledky štúdie, ktorej cieľom bolo overiť bezpečnosť a účinnosť jednorazovej vaginálnej aplikácie 2 % butokonazolnitrátu (Gynazol 2 % vaginálny krém RG) v špecifickom bioadhezívnom vehikule, v liečbe akútnej formy vulvovaginálnej kandidózy. Hodnotilo sa 311 žien. Vylúčené boli ženy s frekvenciou recidív viac ako 4-krát ročne. Design štúdie: Po diagnóze akútnej formy vulvovaginálnej kandidózy lekárom, si poučené pacientky samé aplikovali liečivo do pošvy. V dotazníku zaznamenávali zmeny subjektívnych ťažkostí v štvorbodovej škále, pred aplikáciou, po 20 minútach, po 4 hodinách, po 12 hodinách, po 24 hodinách, po 72 hodinách, na 5. deň a na 7. - 10. deň po aplikácii. Efekt liečby hodnotili následne aj po 30. dňoch po aplikácii. Zmeny objektívneho nálezu hodnotili pri kontrole v ambulancii lekári po 7.- 10. a po 30. dňoch, tiež v štvorbodovej škále. Výsledky: Štúdia potvrdila rýchly nástup úľavy po aplikácii liečiva. U 50 % žien v podstate vymizli ťažkosti do 24 hodín a u 75 % žien do 48 hodín po aplikácii. Po 7. - 10. dňoch uvádzalo zlepšenie 93,3 % žien a po 30. dňoch 94,5 % žien. Lekári pri hodnotení po 7.-10. dňoch konštatovali zlepšenie príznakov u 98,6 % žien a po 30. dňoch u 98,4 % žien. Nedostatočné zlepšenie bolo na 7. deň konštatované u 1,3 % žien, po 30. dňoch u 1,6 %. Úplne chýbanie efektu liečby nezaznamenali lekári ani v jednom prípade.

Objectives: The author presents the results of the study aimed at verifying safety and efficacy of a single-dose vaginal administration of 2 % butoconazole nitrate (vaginal cream Gynazole 2 % RG) in a specific bioadhesive vehicle for treatment of acute vulvo-vaginal candidiasis. This study evaluated 311 female patients excluding those with the frequency of relapses more than 4 times per year. Study Design: After being diagnosed for acute vulvo-vaginal candidiasis the instructed patients self-applied the cream into the vagina. In the questionnaire they rated changes of subjective distress on a 4-point scale: before administration, after 20 minutes, after 4 hours, after 12 hours, after 24 hours, after 72 hours, on the 5th day and 7th - 10th day post-dosing. Effectiveness of treatment was evaluated also at 30 days post-dosing. Physicians assessed changes in objective findings in the follow-up at 7-10 days and 30 days post-dosing with using a 4-point scale as well. Results: The study confirmed fast initial symptom relief after cream administration. 50 % of patients experienced initial symptom relief within 24 hours and 75 % of patients within 48 hours after administration. 93.3 % of patients reported relief within 7- 10 days and 94.5 % within 30 days. Physicians reported relief of symptoms in 98.6 % of patients within 7-10 days and in 98.4 % within 30 days. Insufficient relief was reported in 1.3 % of patients on 7th day and in 1.6 % within 30 days. The total failure of treatment effectiveness was not recorded with respect to all cases.

Prehľad je venovaný vaginálnym liekovým formám počnúc konvenčnými, cez vaginálne inzerty, prstence až po moderné bioadhezívne vaginálne liekové formy s riadeným uvoľňovaním liečiva. Analyzuje vplyv fyzikálnych a chemických vlastností liečiva a typu liekovej formy a jej súčastí - excipientov na farmaceutickú a biologickú dostupnosť aplikovaného liečiva. Posudzuje vplyv rýchlosti uvoľňovania liečiva z liekovej formy a aplikačného miesta i vplyv bioadhézie na topický účinok v nej obsiahnutého liečiva i na možnosti systémového účinku. Charakterizuje bioadhéziu a mukoadhéziu i vhodné typy polymérov vo vzťahu k vaginálnym liekom. Poukazuje na prednosti a nedostatky konvenčných vaginálnych liekových foriem a analyzuje súčasné možnosti moderných vaginálnych liekových foriem i perspektívy vývoja.

The review deals with vaginal dosage forms from conventional dosage forms through vaginal inserts, vaginal rings to bioadhesive vaginal dosage forms with controlled liberation (dissolution) of drugs. It analyses influence of physical - chemical characteristics of drug and type of dosage form and its excipients on the pharmaceutical availability and bioavailability of applied drug. It evaluates effect of dissolution rate of drug from dosage form and the site of application and influence of bioadhesion on the topical and systemic effect of drug. The bioadhesion and mucoadhesion and the bioadhesive polymers are characterized in connection with vaginal dosage form. The advantages and disadvantages of conventional dosage forms are mentioned and the possibilities of modern vaginal dosage forms (drug delivery systems) and future possibilities of development are analyzed.

Přehled shrnuje základní farmaceutické a medicínské informace o doposud dosažených výsledcíchve vývoji bioadhezivních lékových forem s podrobnějším zaměřením na mukoadhezivní orálnítablety. Místem aplikace těchto tablet je lícní kapsa. Díky specifickým vlastnostem slizové vrstvyna bukální sliznici a mukoadhezivních polymerů, ze kterých jsou tablety vyrobeny, dochází k adhezitablet na sliznici, přičemž adheze může trvat určitou dobu a během celé této doby se léčivo postupněuvolňuje. Absorpce léčiva sliznicí dutiny ústní přináší řadu výhod týkajících se zejména stabilityléčiva. Vyvíjí se různé typy mukoadhezivních tablet, velmi výhodný se jeví systém uvolňující léčivopouze jedním směrem, a to přímo do sliznice. Při hodnocení mukoadhezivních tablet jsou důležitézejména dva parametry, bioadhezivní síla a rychlost uvolňování léčiva. Orální mukoadhezivnítablety se mohou uplatnit v léčbě jak systémových, tak i lokálních onemocnění.

The review paper summarizes the principal pharmaceutical and medical information about thehitherto achieved results in the development of bioadhesive dosage form concentrating on mucoad-hesive oral tablets. The site of administration of the tablets is the facial pocket. Due to specificproperties of the mucous layer on the buccal mucosa and mucoadhesive polymers from which thetablets are manufactured, tablets adhere to the mucosa. The adhesion may take a certain period oftime and during the whole period the active ingredient is gradually released. Absorption of the drugthrough the mucous membrane of the oral cavity has a number of advantages, in particular withrespect to the stability of the drug. Various types of mucoadhesive tablets are being developed. Thesystem releasing the drug only in one direction, i.e. direct to the mucosa, seems to be veryadvantageous. In the evaluation of mucoadhesive tablets, two parameters are of particular impor-tance, the bioadhesive force and the rate of drug release. Oral mucoadhesive tablets can be employedin the treatment of both systemic and local diseases.

• MeSH
• aplikace bukální MeSH
• biokompatibilní materiály MeSH
• polymery MeSH
• tablety MeSH
• tkáňová adheziva farmakologie   MeSH
• ústní sliznice cytologie   fyziologie   MeSH
• Publikační typ
• přehledy MeSH