Orally dispersible films (ODFs) prepared by an electrospinning are a novel type of pharmaceutical formulation. This dosage form has the potential to be beneficial for small children and the elderly, who can have problems with administration of classical tablets due to the increased risk of choking and difficulty with swallowing. Due to the highly porous nanofiber morphology, the ODFs examined in this study achieve rapid disintegration into drug microparticles when in contact with saliva. The suspension is then easier to swallow. In this study, we focus on the impact of film composition (polymer matrix composition) on the properties of electrospun membranes. In particular, we prepared ODFs composed of a mixture of PEG 100 000 with HPMC E5 and PVP k90 with HPMC E5. We found significant differences in the structure of electrospinned membranes, where samples containing PEG 100 000 and HPMC E5 exhibited much narrower distribution of fibers. Furthermore, nanofibers containing PVP k90 exhibit a faster disintegration rate, while dissolution of the drug was faster in the case of PEG 100 000 containing ODFs. The improvement was caused by both the structure and composition of the membranes.
- MeSH
- dítě MeSH
- lidé MeSH
- polymery * chemie MeSH
- příprava léků MeSH
- rozpustnost MeSH
- senioři MeSH
- systémy cílené aplikace léků * MeSH
- tablety MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
The development of an ideal vascular prosthesis represents an important challenge in terms of the treatment of cardiovascular diseases with respect to which new materials are being considered that have produced promising results following testing in animal models. This study focuses on nanofibrous polycaprolactone-based grafts assessed by means of histological techniques 10 days and 6 months following suturing as a replacement for the rat aorta. A novel stereological approach for the assessment of cellular distribution within the graft thickness was developed. The cellularization of the thickness of the graft was found to be homogeneous after 10 days and to have changed after 6 months, at which time the majority of cells was discovered in the inner layer where the regeneration of the vessel wall was found to have occurred. Six months following implantation, the endothelialization of the graft lumen was complete, and no vasa vasorum were found to be present. Newly formed tissue resembling native elastic arteries with concentric layers composed of smooth muscle cells, collagen, and elastin was found in the implanted polycaprolactone-based grafts. Moreover, the inner layer of the graft was seen to have developed structural similarities to the regular aortic wall. The grafts appeared to be well tolerated, and no severe adverse reaction was recorded with the exception of one case of cartilaginous metaplasia close to the junctional suture.
- Publikační typ
- časopisecké články MeSH
The purpose of this work is to explore the preparation of nanofibrous orally dispersible films (ODFs) by needleless electrospinning from the active pharmaceutical ingredient (API) Tadalafil using particles suspended in a solution of polymers and other excipients. The prepared films were characterized by a combination of scanning electron microscopy, mechanical tests, measurements of the disintegration time and dissolution characteristic, X-ray diffraction, and differential scanning calorimetry. Furthermore, we investigated the impact of lamination pressures in the range of 0 to 5 bars combined with films at various relative humidity values on the mechanical properties of the ODF. An increase in lamination pressure resulted in higher Young's modulus values, with the maximum value observed for a sample laminated at a pressure of 5 bar and the maximum stress and strain of the prepared ODF at a lamination pressure of 1.2 bar. Moreover, there was a significant increase in the disintegration time with increase in lamination pressure. The disintegration time ranged from 0.35 s for non-laminated samples to 12 s for samples laminated at a pressure of 5 bar. On the contrary, the lamination pressure did not reveal to have any impact on the dissolution kinetics. These results confirmed that the lamination pressure can improve the processability of ODFs without affecting the API dissolution kinetics.
We have prepared a candidate biocompatible construct for skin wound healing based on electrospun polycaprolactone (PCL) nanofibrous membranes. The membrane material was loaded either with L-arginine or with alaptide, or with a mixture of both bioactive components. Alaptide is a spirocyclic synthetic dipeptide, an analogue of melanocyte-stimulating hormone release-inhibiting factor. L-arginine is an amino acid with a basic guanidine side chain. It is a direct precursor of nitric oxide, which plays a pivotal role in skin repair. The presence and the distribution of the additives were proved with high-performance liquid chromatography, Fourier-transform infrared spectroscopy and Raman spectroscopy. The influence of L-arginine and alaptide on the morphology of the membrane was characterized using scanning electron microscopy. No statistically significant correlation between fiber diameter and drug concentration was observed. The membranes were then tested in vitro for their cytotoxicity, using primary human dermal fibroblasts, in order to obtain the optimal concentrations of the additives for in vivo tests in a rat model. The membranes with the highest concentration of L-arginine (10 wt. %) proved to be cytotoxic. The membranes with alaptide in concentrations from 0.1 to 2.5 wt.%, and with the other L-arginine concentrations (1 and 5 wt.%), did not show high toxicity. In addition, there was no observed improvement in cell proliferation on the membranes. The in vivo experiments revealed that membranes with 1.5 wt.% of alaptide or with 1.5 wt.% of alaptide in combination with 5 wt.% of L-arginine markedly accelerated the healing of skin incisions, and particularly the healing of skin burns, i.e. wounds of relatively large extent. These results indicate that our newly-developed nanofibrous membranes are promising for treating wounds with large damaged areas, where a supporting material is needed.
- MeSH
- arginin chemie MeSH
- biokompatibilní materiály chemie MeSH
- cyklické peptidy chemie MeSH
- elektrochemie MeSH
- elektrody MeSH
- fibroblasty účinky léků MeSH
- fluorescenční mikroskopie MeSH
- hojení ran účinky léků MeSH
- krysa rodu rattus MeSH
- kůže patologie MeSH
- lidé MeSH
- nanovlákna chemie MeSH
- neuropeptidy chemie MeSH
- peptidy chemie MeSH
- potkani Wistar MeSH
- proliferace buněk MeSH
- Ramanova spektroskopie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- systémy cílené aplikace léků MeSH
- techniky in vitro MeSH
- testování materiálů MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury chemie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Polycaprolactone (PCL) was electrospun with the addition of arginine (Arg), an α-amino acid that accelerates the healing process. The efficient needleless electrospinning technique was used for the fabrication of the nanofibrous layers. The materials produced consisted mainly of fibers with diameters of between 200 and 400 nm. Moreover, both microfibers and beads were present within the layers. Higher bead sizes were observed with the increased addition of arginine. The arginine content within the layers as well as the weight of the resultant electrospun materials were enhanced with the increased addition of arginine to the electrospinning solution (1, 5 and 10 wt%). The PCL + 1% Arg nanofibrous layer contained 5.67 ± 0.04% of arginine, the PCL + 5% Arg layer 22.66 ± 0.24% of arginine and the PCL + 10% Arg layer 37.33 ± 0.39% of arginine according to the results of the elemental analysis. A high burst release within 5 h of soaking was recorded for the PCL + 5% and PCL + 10% nanofibrous layers. However, the release rate of arginine from the PCL + 1% Arg was significantly slower, reaching a maximum level after 72 h of soaking. The resulting materials were hydrophobic. Hemocompatibility testing under static conditions revealed no effect on hemolysis following the addition of arginine and the prolongation of the prothrombin time with the increased addition of arginine, thus exerting an influence on the extrinsic and common pathway of coagulation activation. The results of the dynamic hemocompatibility assessment revealed that the numbers of blood cells and platelets were not affected significantly by the various electrospun samples during incubation. The TAT, β-thromboglobulin and SC5-b9 concentrations were characterized by a moderate increase in the PCL group compared to those of the control group. The presence of arginine resulted in a decrease in the investigated hemocompatibility markers. The PMN elastase levels were comparable with respect to all the groups.
- MeSH
- arginin chemie MeSH
- biokompatibilní materiály chemie MeSH
- elektřina MeSH
- hemolýza * MeSH
- hojení ran * MeSH
- lidé MeSH
- nanovlákna chemie MeSH
- polyestery chemie MeSH
- protrombinový čas MeSH
- testování materiálů metody MeSH
- tkáňové inženýrství MeSH
- tkáňové podpůrné struktury chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The study involved the electrospinning of the copolymer poly(L-lactide-co-ε-caprolactone) (PLCL) into tubular grafts. The subsequent material characterization, including micro-computed tomography analysis, revealed a level of porosity of around 70%, with pore sizes of 9.34 ± 0.19 μm and fiber diameters of 5.58 ± 0.10 μm. Unlike fibrous polycaprolactone, the electrospun PLCL copolymer promoted fibroblast and endothelial cell adhesion and proliferation in vitro. Moreover, the regeneration of the vessel wall was detected following implantation and, after six months, the endothelialization of the lumen and the infiltration of arranged smooth muscle cells producing collagen was observed. However, the degradation rate was found to be accelerated in the rabbit animal model. The study was conducted under conditions that reflected the clinical requirements-the prostheses were sutured in the end-to-side fashion and the long-term end point of prosthesis healing was assessed. The regeneration of the vessel wall in terms of endothelialization, smooth cell infiltration and the presence of collagen fibers was observed after six months in vivo. A part of the grafts failed due to the rapid degradation rate of the PLCL copolymer.
- MeSH
- aorta patologie MeSH
- arteriae carotides patologie MeSH
- buněčná adheze MeSH
- buňky 3T3 MeSH
- cévní protézy * MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- endoteliální buňky MeSH
- fibroblasty cytologie MeSH
- kolagen metabolismus MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myocyty hladké svaloviny cytologie MeSH
- myši MeSH
- polyestery chemie MeSH
- polymery chemie MeSH
- poréznost MeSH
- prasata MeSH
- psi MeSH
- regenerace MeSH
- rentgenová mikrotomografie MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury MeSH
- transplantace cév * MeSH
- zobrazování trojrozměrné MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Biodegradable polyesters, namely polycaprolactone (PCL) and copolymer of polylactide and polycaprolactone (PLCL) were electrospun into various fibrous structures and their hemocompatibility was evaluated in vitro. Firstly, hemolytic effect was evaluated upon incubation with diluted whole blood. The results showed that the degree of hemolysis depended on chemical composition and fibrous morphology. Electrospun polycaprolactone induced slight degree of hemolysis depending on its molecular weight and fibrous morphology; copolymer PLCL did not cause detectable hemolysis. The influence of coagulation pathways was examined by measurement of coagulation times. It was showed that intrinsic coagulation pathway assessed by activated partial thromboplastin time (APTT) was moderately accelerated after incubation with PCL and prolonged after incubation with copolymer PLCL. Extrinsic activation of coagulation tested by prothrombin time (PT) was slightly accelerated after incubation with all tested electrospun samples. Thrombogenicity assessment of fibrous samples revealed high thrombogenic properties of fibrous materials that was comparable to high degree of collagen thrombogenicity. The level of platelet activation was dependent on chemical composition and surface morphology of tested materials.
- MeSH
- biokompatibilní materiály chemická syntéza chemie farmakologie MeSH
- hemolýza účinky léků MeSH
- kolagen chemie MeSH
- krevní buňky cytologie účinky léků metabolismus MeSH
- lidé MeSH
- mikroskopie elektronová rastrovací MeSH
- parciální tromboplastinový čas MeSH
- polyestery chemie MeSH
- polymery chemická syntéza chemie MeSH
- protrombinový čas MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
