Periodontal disease is a widespread chronic condition associated with degradation of periodontal tissues that requires more effective approaches for its treatment. Thus, the aim was to develop a nanodelivery system for local application of antimicrobials, with evaluation in vitro using a newly developed micro flow-through apparatus that simulates local in-vivo conditions in the periodontal pocket: small resting volume, and low gingival crevicular fluid flow rate. We successfully developed a double-layer nanofiber mat composed of a chitosan/ poly(ethylene) oxide nanofiber layer with 30% ciprofloxacin, and a poly(epsilone-caprolactone) nanofiber layer with 5% metronidazole. The precisely designed composition enabled sustained in-vitro release of the antimicrobials according to their specific drug-release mechanisms. The rate-limiting step of ciprofloxacin release was its own low solubility at pH 7.4, when there was excess of solid drug present in the delivery system. In contrast, sustained release of metronidazole was due to slow penetration of dissolution medium through the hydrophobic poly(%-caprolactone) nanofiber layer. The double-layer nanofiber mat developed showed antibacterial activity against Escherichia coli and Aggregatibacter actinomycetemcomitans based on plate antibiogram assays. The antimicrobial concentrations released from the nanofiber mats determined using the developed apparatus were above the MICs against these periodontal pathogens for up to 7 days, which is valuable information for prediction of the efficacy of the nanodelivery system. Although this apparatus was specifically designed for characterization of formulations associated with treatments for periodontal disease, its applicability is much wide, as for development of any delivery system for application at target sites that have similar local conditions.
COBISS.SI-ID: 4838257
Complexation of linear alginate polyanions with different classes of crosslinkers (divalent cations, polycations, positively charged surfactants) was investigated, to unravel their effects on nanoparticle formation. The goal was to define the crosslinker-to-alginate molar ratios at which nanoparticles are formed, and to reveal the underlying thermodynamics and molecular interactions using dynamic and electrophoretic light scattering, isothermal titration calorimetry, and infrared spectroscopy. Alginate nanoparticles were formed across a limited range of molar ratios that was specific for each crosslinker, and had different size and stability. Thermodynamic parameters of alginate complexation with crosslinkers showed that nanoparticle formation was in all cases entropy driven, together with a minor enthalpic contribution. The crosslinking mechanism was based on ionic interactions, with accompanying weaker interactions specific for each crosslinker, and involved characteristic macroscopic association constants (Ka1) for complexation of alginate (range, 104%109 M%1). Additionally, the ionic strengths of the media influenced the characteristics and stabilities of the polyelectrolyte nanoparticles.
COBISS.SI-ID: 4413297
The paper presents the effect of polymer solution composition on the morphology, mechanical properties and drug permeability of the asymmetric polyamide 6 (PA6) membranes prepared by immersion precipitation. The effect of polymer solution composition on morphology, mechanical properties and permeability of the produced membrane is considered, since these properties are of relevance for drug delivery applications. PA6-formic acid-deionized water solutions were used to prepare membranes for further characterization with differential scanning calorimetry and scanning electron microscopy for morphology analysis, tensile testing and drug permeability tests. The results show that the amount of PA6 does not significantly affect morphology of the membrane, while having pronounced effect on tensile elastic modulus (50% increase). On the other hand, the concentration of formic acid in solution (dissolution intensity) influences crystallization dynamics and significantly changes the morphology of membrane (in the range of approximately 75-100 wt% of formic acid concentrations), consequently having effect on drug permeability.
COBISS.SI-ID: 16094747
The air-liquid RPMI 2650 cell model was found to be a promising pharmacological model for the nasal epithelial barrier and much more suitable than the liquid-liquid model for nasal drug permeability prediction. Their suitability was investigated according to the regulatory guidelines for in vitro permeability methods for drug permeability classification. The permeability of 23 model drugs and several zero permeability markers across the cell models was measured and correlations with the fully differentiated nasal epithelial model (MucilAirâ„¢), the Caco-2 cells and isolated rat jejunum were established.
COBISS.SI-ID: 1518174
Background The number of authorized orphan and non-orphan medicines for rare diseases has increased in Europe. Patient access to these medicines is affected by high costs, weak efficacy/safety evidence, and societal value. European health care systems must determine whether paying for expensive treatments for only a few patients is sustainable. Objectives This study aimed to evaluate patient access to orphan and non-orphan medicines for rare diseases in 22 European countries during 2005 to 2014. Methods Medicines for rare diseases from the Orphanet list, authorized during 2005 to 2014, were searched for in the IMS MIDAS Quarterly Sales Data, January 2005 - December 2014 (IQVIA, Danbury, CT). The following three measures were determined for each country: number of available medicines, median time to continuous use, and medicine expenditure. A medicine was considered available if uninterrupted sales within a 1-year period were detected. Results From 2005 to 2014, 125 medicines were authorized and 112 were found in the search. Of those, between 70 (63%) and 102 (91%) were available in Germany, the United Kingdom, Italy, France, and the Scandinavian countries. These countries were also the fastest to enable continuous use (3%9 mo). Only 27% to 38% of authorized medicines were available in Greece, Ireland, Bulgaria, Romania, and Croatia, which took 1 to 2.6 years to begin continuous use. A country%s expenditure on medicines for rare diseases in 2014 ranged between %0.2 and...
COBISS.SI-ID: 4490097