A new solution for local anesthetic and antibiotic delivery after eye surgery is presented. A contact lens-shaped collagen drug carrier was created and loaded by Levofloxacin and Tetracaine with a riboflavin crosslinked surface layer, thus impeding diffusion. The crosslinking was confirmed by Raman spectroscopy, whereas the drug release was investigated using UV-Vis spectrometry. Due to the surface barrier, the drug gradually releases into the corneal tissue. To test the function of the carrier, a 3D printed device and a new test method for a controlled drug release, which mimics the geometry and physiological lacrimation rate of the human eye, were developed. The experimental setup with simple geometry revealed that the prepared drug delivery device can provide the prolonged release profile of the pseudo-first-order for up to 72 h. The efficiency of the drug delivery was further demonstrated using a dead porcine cornea as a drug recipient, without the need to use live animals for testing. Our drug delivery system significantly surpasses the efficiency of antibiotic and anesthetic eyedrops that would have to be applied approximately 30 times per hour to achieve the same dose as that delivered continuously by our device.
- Publikační typ
- časopisecké články MeSH
A little is known about the link between the macromolecular architecture of dialdehyde polysaccharides (DAPs), their crosslinking capabilities, and the properties of resulting hydrogels. Here, DAPs based on cellulose, dextrin, dextran, and hyaluronate were compared as crosslinkers for poly(vinyl alcohol), PVA. The swelling, network parameters, viscoelastic properties, porosity, and cytotoxicity of PVA/DAP hydrogels were investigated concerning the crosslinker structure, molecular weight, aldehyde group density per macromolecule, and the size of spontaneously formed crosslinker nano-assemblies. Generally, crosslinkers based on linear polysaccharides (cellulose, hyaluronate) performed more reliably, while the presence of branching could be both beneficial (dextran) but also detrimental (dextrin) at lower crosslinker concentrations. For example, the hydrogel swelling differed by up to one-third (600 vs. 400%) and storage modulus even by up to one half (~7000 vs. ~3500 Pa) depending on crosslinker structure and properties. These differences were rationalized by variances in crosslinking modes derived based on obtained data.
- MeSH
- buňky NIH 3T3 MeSH
- hydrogely chemie farmakologie MeSH
- myši MeSH
- polysacharidy chemie farmakologie MeSH
- polyvinylalkohol chemie farmakologie MeSH
- reagencia zkříženě vázaná chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Study provides an in-depth analysis of the structure-function relationship of polysaccharide anticancer drug carriers and points out benefits and potential drawbacks of differences in polysaccharide glycosidic bonding, branching and drug binding mode of the carriers. Cellulose, dextrin, dextran and hyaluronic acid have been regioselectively oxidized to respective dicarboxylated derivatives, allowing them to directly conjugate cisplatin, while preserving their major structural features intact. The structure of source polysaccharide has crucial impact on conjugation effectiveness, carrier capacity, drug release rates, in vitro cytotoxicity and cellular uptake. For example, while branched structure of dextrin-based carrier partially counter the undesirable initial burst release, it also attenuates the cellular uptake and the cytotoxicity of carried drug. Linear polysaccharides containing β-(1→4) glycosidic bonds and oxidized at C2 and C3 (cellulose and hyaluronate) have the best overall combination of structural features for improved drug delivery applications including potentiation of the cisplatin efficacy towards malignances.
- MeSH
- antitumorózní látky aplikace a dávkování MeSH
- buňky NIH 3T3 MeSH
- celulosa chemie MeSH
- cisplatina aplikace a dávkování MeSH
- dextrany chemie MeSH
- dextriny chemie MeSH
- glykosidy chemie MeSH
- inhibiční koncentrace 50 MeSH
- kyselina hyaluronová chemie MeSH
- kyslík chemie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- myši MeSH
- nosiče léků * MeSH
- oxidace-redukce MeSH
- platina chemie MeSH
- polysacharidy chemie MeSH
- systémy cílené aplikace léků * MeSH
- techniky in vitro MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Various design and fabrication strategies of carrier-based drug delivery systems have been quickly established and applied for cancer therapy in recent years. These systems contribute greatly to current cancer treatments but further development needs to be made to eliminate obstacles such as low drug loading capacity and severe side effects. To achieve better drug delivery, we propose an innovative strategy for the construction of easy manufactured drug self-delivery systems based on molecular structures, which can be used for the co-delivery of curcuminoids and all the nitrogen-containing derivatives of camptothecin for better targeted cancer therapy with minimized side effects. The formation mechanism investigation demonstrates that the rigid planar structures of camptothecin derivatives and curcuminoids with relevant leaving hydrogens make it possible for them to be assembled into nanoparticles under suitable conditions. These nanoparticles show stabilized particle sizes (100 nm) under various conditions and tunable surface charges which increase from around -10 mV in a normal physiological condition (pH 7.4) to +40 mV under acidic tumor environments. In addition, in vivo mice experiments have demonstrated that, compared to irinotecan (a derivative of camptothecin) itself, the co-delivered irinotecan curcumin nanoparticles exhibited significantly enhanced lung and gallbladder targeting, improved macrophage-clearance escape and ameliorated colorectal cancer treatment with an eradication of life-threatening diarrhea, bringing hope for better targeted chemotherapy and clinical translation. Lastly, the strategy of structure based design of drug self-delivery systems may inspire more research and discoveries of similar self-delivered nano systems for wider pharmaceutical applications.
- MeSH
- antitumorózní látky * terapeutické užití MeSH
- kamptothecin MeSH
- léčivé přípravky * MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory * farmakoterapie MeSH
- nanočástice * MeSH
- systémy cílené aplikace léků * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
2,3-Dialdehyde cellulose (DAC) was used as an efficient and low-toxicity crosslinker to prepare thin PVA/DAC hydrogel films designed for topical applications such as drug-loaded patches, wound dressings or cosmetic products. An optimization of hydrogel properties was achieved by the variation of two factors - the amount of crosslinker and the weight-average molecular weight (Mw) of the source PVA. The role of each factor to network parameters, mechanical, rheological and surface properties, hydrogel porosity and transdermal absorption is discussed. The best results were obtained for hydrogel films prepared using 0.25 wt% of DAC and PVA with Mw = 130 kDa, which had a high porosity and drug-loading capacity (high water content), mechanical properties allowing easy handling, best adherence to the skin from all tested samples and improved transdermal drug-delivery. Hydrogel films are biocompatible, show no cytotoxicity and have no negative impact on cell growth and morphology in their presence. Furthermore, hydrogels do not support cell migration and attachment to their surface, which should ensure easy removal of hydrogel patches even from wounded or damaged skin after use.
- MeSH
- celulosa analogy a deriváty MeSH
- hydrogely MeSH
- obvazy * MeSH
- polyvinylalkohol * MeSH
- Publikační typ
- časopisecké články MeSH
The synthesis of selectively oxidized cellulose, 2,3-dicarboxycellulose (DCC), is optimized for preparation of highly oxidized material for biological applications, which includes control over the molecular weight of the product during its synthesis. Conjugates of DCC and cisplatin simultaneously offer a very high drug binding efficiency (>90%) and drug loading capacity (up to 50 wt %), while retaining good aqueous solubility. The adjustable molecular weight of the DCC together with variances in drug feeding ratio allows to optimize cisplatin release profiles from delayed (<2% of cisplatin released during 6 h) to classical burst release with more than 60% of cisplatin released after 24 h. The release rates are also pH-dependent (up to 2 times faster release at pH 5.5 than at pH 7.4), which allows to exploit the acidic nature of tumor microenvironment. Extensive in vitro studies were performed on eight different cell lines for two cisplatin-DCC conjugates with different release profiles. In comparison with free cisplatin, both cisplatin-DCC conjugates demonstrated considerably lower cytotoxicity toward healthy cells. Conjugates with burst release profiles were found more effective against prostate cell lines, while DCC conjugates with slower release were more cytotoxic against ovarian and lung carcinoma cell lines. In vivo studies indicated a significantly longer survival rate, a reduction in tumor volume, and a higher accumulation of platinum in tumors of mice treated with the cisplatin-DCC conjugate in comparison to those treated by free cisplatin.
- MeSH
- antitumorózní látky * chemie farmakokinetika farmakologie MeSH
- buňky NIH 3T3 MeSH
- buňky PC-3 MeSH
- celulosa * chemie farmakokinetika farmakologie MeSH
- cisplatina * chemie farmakokinetika farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- léky s prodlouženým účinkem chemie farmakokinetika farmakologie MeSH
- lidé MeSH
- myši MeSH
- nádorové mikroprostředí účinky léků MeSH
- nádory * farmakoterapie metabolismus patologie MeSH
- oxidace-redukce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hybrid inorganic-organic fillers based on nanostructured silver/zinc oxide decorations on micro-cellulose carrier particles were prepared by stepwise microwave assisted hydrothermal synthesis using soluble salts as precursors of silver and zinc oxide. Hexamethylenetetramine was used as precipitating agent for zinc oxide and reducing agent for silver. The inorganics covered all available surfaces of the cellulose particles with a morphology resembling a coral reef. Prepared particulate fillers were compounded to medical grade poly(vinyl chloride) matrix. Scanning electron microscopy and powder X-ray diffractometry were used to investigate the morphology and crystalline phase structure of fillers. The scanning electron microscopy was used for morphological study of composites. With respect to prospective application, the composites were tested on electrical and antibacterial properties. A small effect of water absorption in polymer composites on their dielectric properties was observed but no adverse effect of water exposure on prepared materials was manifested. Electrical conductivity of fillers and composites was measured and no influence of water soaking of composites was found at all. The surface antibacterial activity of prepared composites was evaluated according to the standard ISO 22196. Excellent performance against Escherichia coli and very high against Staphylococcus aureus was achieved.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- biokompatibilní materiály chemická syntéza MeSH
- celulosa chemie MeSH
- fyziologie bakterií účinky léků MeSH
- kovové nanočástice chemie ultrastruktura MeSH
- nanokompozity chemie ultrastruktura MeSH
- oxid zinečnatý chemie MeSH
- polyvinylchlorid chemie MeSH
- povrchové vlastnosti MeSH
- prášky, zásypy, pudry MeSH
- stříbro chemie farmakologie MeSH
- testování materiálů MeSH
- velikost částic MeSH
- viabilita buněk fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Three different ZnO-based antibacterial fillers having different morphologies in microscale region were prepared by the use of the microwave assisted synthesis protocol created in our laboratory with additional annealing in one case. Further, PVC composites containing 0.5-5 wt.% of ZnO based antibacterial fillers were prepared by melt mixing and characterized by scanning electron microscopy (SEM) and X-ray diffractometry (XRD). Mechanical testing showed no adverse effect on the working of polymer composites due to either of the fillers used or the applied processing conditions in comparison with the neat medical grade PVC. The surface antibacterial activity of the compounded PVC composites was assessed against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 6538P according to ISO 22196: 2007 (E). All materials at almost all filler loading levels were efficient against both species of bacteria. The material with the most expanding morphology assuring the largest contact between filler and matrix achieved an excellent level of more than 99.9999% reduction of viable cells of E. coli in comparison to untreated PVC and performed very well against S. aureus, too. A correlation between the morphology and efficacy of the filler was observed and, as a result, a general rule was formulated which links the proneness of the microparticles to perform well against bacteria to their shape and morphology.
This paper reports the substitution of polyolefin backbone binder components with low melting temperature carnauba wax for powder injection moulding applications. The effect of various binder compositions of Al₂O₃ feedstock on thermal degradation parameters is investigated by thermogravimetric analysis. Within the experimental framework 29 original feedstock compositions were prepared and the superiority of carnauba wax over the polyethylene binder backbone was demonstrated in compositions containing polyethylene glycol as the initial opening agent and governing the proper mechanism of the degradation process. Moreover, the replacement of synthetic polymer by the natural wax contributes to an increase of environmental sustainability of modern industrial technologies.
- MeSH
- finanční podpora výzkumu jako téma MeSH
- Publikační typ
- abstrakty MeSH
