Nanofibre-based mucoadhesive films were invented for oromucosal administration of nanocarriers used for delivery of drugs and vaccines. The mucoadhesive film consists of an electrospun nanofibrous reservoir layer, a mucoadhesive film layer and a protective backing layer. The mucoadhesive layer is responsible for tight adhesion of the whole system to the oral mucosa after application. The electrospun nanofibrous reservoir layer is intended to act as a reservoir for polymeric and lipid-based nanoparticles, liposomes, virosomes, virus-like particles, dendrimers and the like, plus macromolecular drugs, antigens and/or allergens. The extremely large surface area of nanofibrous reservoir layers allows high levels of nanoparticle loading. Nanoparticles can either be reversibly adsorbed to the surface of nanofibres or they can be deposited in the pores between the nanofibres. After mucosal application, nanofibrous reservoir layers are intended to promote prolonged release of nanoparticles into the submucosal tissue. Reversible adsorption of model nanoparticles as well as sufficient mucoadhesive properties were demonstrated. This novel system appears appropriate for the use in oral mucosa, especially for sublingual and buccal tissues. To prove this concept, trans-/intramucosal and lymph-node delivery of PLGA-PEG nanoparticles was demonstrated in a porcine model. This system can mainly be used for sublingual immunization and the development of "printed vaccine technology".
- MeSH
- adheziva chemie MeSH
- aplikace bukální MeSH
- aplikace sublinguální MeSH
- léčivé přípravky aplikace a dávkování MeSH
- liposomy chemie MeSH
- lymfatické uzliny metabolismus MeSH
- myši MeSH
- nanočástice chemie MeSH
- nanovlákna chemie MeSH
- polyethylenglykoly chemie MeSH
- polyglactin 910 chemie MeSH
- prasata MeSH
- systémy cílené aplikace léků metody MeSH
- ústní sliznice metabolismus MeSH
- vakcinace metody MeSH
- vakcíny aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
CONTEXT: Mucoadhesive oral films, with their prolonged residence time at the site of application, offer a promising approach for protection of the oral lesion surface. The addition of sodium hyaluronate of different molecular weights as a second mucoadhesive polymer into the film matrix could positively influence the physico-mechanical and mucoadhesive properties of films. OBJECTIVE: The aim of this study was to investigate the formulation of a monolayered film matrix containing varying amounts of sodium hyaluronate and to test the properties of such matrices by applying different characterization methods. MATERIALS AND METHODS: Film matrix was composed of two mucoadhesive polymers, carmellose sodium and sodium hyaluronate, plasticized with glycerol. Resulting films were characterized with regard to their viscosity and physico-mechanical properties. RESULTS AND DISCUSSION: Multivariate data analysis was employed to evaluate the influence of varying amounts of mucoadhesive polymers on the main mucoadhesive oral films' properties. The lower content of sodium hyaluronate caused improvements in mechanical properties and residence time on the artificial oral mucosa, both of which are the main characteristics that determine the quality of the final product. CONCLUSIONS: The best results were obtained by samples containing carmellose sodium with a small amount of sodium hyaluronate (about 0.5% in casting dispersion).
- MeSH
- adheziva chemie metabolismus MeSH
- adhezivita MeSH
- glycerol chemie metabolismus MeSH
- kyselina hyaluronová chemie metabolismus MeSH
- lidé MeSH
- multivariační analýza MeSH
- orální absorpce MeSH
- pevnost v tahu MeSH
- polymery MeSH
- sodná sůl karboxymethylcelulosy chemie metabolismus MeSH
- systémy cílené aplikace léků metody MeSH
- ústní sliznice metabolismus MeSH
- uvolňování léčiv MeSH
- viskozita MeSH
- zvláčňovadla chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Mucoadhesive buccal films (MBFs) provide an innovative way to facilitate the efficient site-specific delivery of active compounds while simultaneously separating the lesions from the environment of the oral cavity. The structural diversity of these complex multicomponent and mostly multiphase systems as well as an experimental strategy for their structural characterization at molecular scale with atomic resolution were demonstrated using MBFs of ciclopirox olamine (CPX) in a poly(ethylene oxide) (PEO) matrix as a case study. A detailed description of each component of the CPX/PEO films was followed by an analysis of the relationships between each component and the physicochemical properties of the MBFs. Two distinct MBFs were identified by solid-state NMR spectroscopy: (i) at low API (active pharmaceutical ingredient) loading, a nanoheterogeneous solid solution of CPX molecularly dispersed in an amorphous PEO matrix was created; and (ii) at high API loading, a pseudoco-crystalline system containing CPX-2-aminoethanol nanocrystals incorporated into the interlamellar space of a crystalline PEO matrix was revealed. These structural differences were found to be closely related to the mechanical and physicochemical properties of the prepared MBFs. At low API loading, the polymer chains of PEO provided sufficient quantities of binding sites to stabilize the CPX that was molecularly dispersed in the highly amorphous semiflexible polymer matrix. Consequently, the resulting MBFs were soft, with low tensile strength, plasticity, and swelling index, supporting rapid drug release. At high CPX content, however, the active compounds and the polymer chains simultaneously cocrystallized, leaving the CPX to form nanocrystals grown directly inside the spherulites of PEO. Interfacial polymer-drug interactions were thus responsible not only for the considerably enhanced plasticity of the system but also for the exclusive crystallization of CPX in the thermodynamically most stable polymorphic form, Form I, which exhibited reduced dissolution kinetics. The bioavailability of CPX olamine formulated as PEO-based MBFs can thus be effectively controlled by inducing the complete dispersion and/or microsegregation and nanocrystallization of CPX olamine in the polymer matrix. Solid-state NMR spectroscopy is an efficient tool for exploring structure-property relationships in these complex pharmaceutical solids.
- MeSH
- adheziva chemie metabolismus MeSH
- biologická dostupnost MeSH
- chemie farmaceutická metody MeSH
- ethylenoxid chemie MeSH
- krystalizace metody MeSH
- magnetická rezonanční spektroskopie metody MeSH
- nanočástice chemie MeSH
- orální absorpce fyziologie MeSH
- polyethylenglykoly chemie metabolismus MeSH
- polymery chemie MeSH
- pyridony chemie MeSH
- rozpustnost MeSH
- ústní sliznice metabolismus MeSH
- uvolňování léčiv fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- adheziva * chemie MeSH
- chemie farmaceutická MeSH
- estery kyseliny mravenčí MeSH
- farmaceutická technologie MeSH
- hydrofobní a hydrofilní interakce MeSH
- kyselina mléčná MeSH
- kyselina polyglykolová MeSH
- nosiče léků * chemie MeSH
- polyestery * chemie MeSH
- reologie MeSH
- rozpouštědla MeSH
- rozpustnost MeSH
- sliznice MeSH
- uvolňování léčiv MeSH
- zvláčňovadla chemie MeSH
Mucoadhesive films represent the most developed medical form of buccal application. Despite the intense focus on buccal film-based systems, there are no standardized methods for their evaluation, which limits the possibility of comparison of obtained data and evaluation of the significance of influence of formulation and process variables on properties of resulting films. The used principal component analysis, together with a partial least squares regression provided a unique insight into the effects of in vitro parameters of mucoadhesive buccal films on their in vivo properties and into interdependencies among the studied variables. In the present study eight various mucoadhesive buccal films based on mucoadhesive polymers (carmellose, polyethylene oxide) were prepared using a solvent casting method or a method of impregnation, respectively. An ethylcellulose or hydrophobic blend of white beeswax and white petrolatum were used as a backing layer. The addition of polyethylene oxide prolonged the in vivo film residence time (from 53.24±5.38-74.18±5.13 min to 71.05±3.15-98.12±1.75 min), and even more when combined with an ethylcellulose backing layer (98.12±1.75 min) and also improved the film's appearance. Tested non-woven textile shortened the in vivo film residence time (from 74.18±5.13-98.12±1.75 min to 53.24±5.38-81.00±8.47 min) and generally worsened the film's appearance. Mucoadhesive buccal films with a hydrophobic backing layer were associated with increased frequency of adverse effects.
- MeSH
- adheziva aplikace a dávkování chemie metabolismus MeSH
- adhezivita účinky léků MeSH
- aplikace bukální MeSH
- chemie farmaceutická MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- multivariační analýza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sodná sůl karboxymethylcelulosy aplikace a dávkování chemie metabolismus MeSH
- ústní sliznice účinky léků metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Three oligoesters with different molar mass and degree of branching, intended as drug carriers, were synthesized and their thermal, rheological, adhesive, and drug release properties were studied. Triethyl citrate, ethyl pyruvate, ethyl salicylate, methyl salicylate, triacetin and tributyrin at a concentration of 20% were tested as plasticizers to improve drug incorporation, and application of the polymeric system. All of the tested plasticizers significantly depressed the Tg by at least 25.5°C. Plasticized oligoesters possessed remarkable adhesive properties on mucin in vitro, the adhesion is at least twofold bigger than it is for gels of cellulose derivatives. It was demonstrated that adhesivity increased with decreasing viscosity of oligoester matrices. In vitro dissolution tests of the flat matrices showed the prolongation of fluconazole release up to over 3 days for the oligoester carrier with the highest molar weight and degree of branching. Depending on the matrix hydrophilization, plasticizing led to an acceleration of the fluconazole release, the 3-h burst effect increased three times.
- MeSH
- adheziva chemie terapeutické užití MeSH
- dentin účinky léků MeSH
- lidé MeSH
- složené pryskyřice chemie terapeutické užití MeSH
- zubní sklovina účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- hodnotící studie MeSH
Byla studována adhezivita větvených oligoesterů v podmínkách in vitro měřením maximální síly potřebné k odtržení testovaného vzorku od podkladu (Fmax) za různých testovacích podmínek. Větvené oligoestery byly syntetizovány z kyseliny mléčné a glykolové v molárním poměru 1:1 a mannitolu nebo dipentaerythritolu jako větvící složky v koncentraci 3 %, 5 % nebo 8 %. Pro snížení viskozity, a tím usnadnění zpracovatelnosti a aplikace byl použit triethyl–citrát (TEC) v koncentraci 30 %. Polymerní systémy pro měření adhezivity byly připraveny tavením oligoesterů v mikrovlnné troubě a důkladnou homogenizací s TEC. Adhezivní síla byla měřena na materiálovém zkušebním stroji T1-FR050TH.A1K Zwick/Roell při nastavené rychlosti odtržení 10 mm/min nebo 100 mm/min, kontaktní síle 10 N nebo 20 N a době kontaktu vzorku s podkladem 5 s nebo 10 s. Bylo zjištěno, že adhezivita větvených oligoesterů je významně vyšší než adhezivita gelů želatiny, methylcelulosy, karmelosy sodné soli nebo karbomeru sodné soli. Oligoestery větvené dipentaerythritolem vykazovaly vyšší adhezivní sílu než oligoestery větvené mannitolem. S rostoucí koncentrací větvící složky v oligoesteru se zvyšovala hodnota adhezivní síly. Z testovaných zkušebních parametrů byl zjištěn statisticky významný vliv rychlosti odtržení vzorku od podkladu na velikost Fmax. Vliv různé doby kontaktu se projevil pouze u některých vzorků a vliv různé kontaktní síly na hodnotu Fmax nebyl prokázán u žádného vzorku.
Adhesive force of branched oligoesters under the in vitro conditions was studied by measuring the maximal force necessary to separate the tested sample from the base (Fmax) under different testing conditions. Branched oligoesters were synthesized from lactic and glycolic acids in the molar ratio 1:1, and from mannitol or dipentaery thritol as the branching components in concentrations of 3%, 5% or 8%. To decrease viscosity and thus to facilitate the workability and administration, triethyl citrate (TEC) in a concentration of 30% was employed. Polymeric systems for adhesive force measurements were prepared by melting oligoesters in a micro oven and by homogenization with TEC. Adhesive force was measured on a material testing device T1-FR050TH.A1K Zwick/Roell at the set rate of separation 10 mm/min or 100 mm/min, contact force 10 N or 20 N, and a period of contact of the sample with the base of 5 s or 10 s. The adhesive force of branched oligoesters was found to be significantly higher than the adhesive force of gelatine gels, methylcellulose, carmelose sodium salt or sodium carbomer salt. Dipentaerythritol-branched oligoesters exerted higher adhesive force than mannitol-branched oligoesters. The value of adhesive force was increased with growing concentration of the branching component in the oligoester. Of the experimental parameters tested, a statistically significant influence of the separation rate of the sample from the base on the magnitude of Fmax was observed. The influence of different periods of contacts was manifested only in some samples, and the influence of different contact forces on Fmax value was not demonstrated in any sample.
- MeSH
- adheziva analýza chemie MeSH
- adhezivita účinky léků MeSH
- finanční podpora výzkumu jako téma MeSH
- klinické laboratorní techniky přístrojové vybavení využití MeSH
- kyselina mléčná analýza chemie MeSH
- nosiče léků aplikace a dávkování MeSH
- polymery analýza chemie MeSH
- techniky in vitro MeSH
- Publikační typ
- srovnávací studie MeSH
