The widespread of bacterial infections including biofilms drives the never-ending quest for new antimicrobial agents. Among the great variety of nanomaterials, carbon dots (CDs) are the most promising antibacterial material, but still require the adjustment of their surface properties for enhanced activity. In this contribution, we report a facile functionalization method of carbon dots (CDs) by tetraalkylammonium moieties using diazonium chemistry to improve their antibacterial activity against Gram-positive and Gram-negative bacteria. CDs were modified by novel diazonium salts bearing tetraalkylammonium moieties (TAA) with different alkyl chains (C2, C4, C9, C12) for the optimization of antibacterial activity. Variation of the alkyl chain allows to reach the significant antibacterial effect for CDs-C9 towards Gram-positive Staphylococcus aureus (S. aureus) (MIC = 3.09 ± 1.10 μg mL-1) and Gram-negative Escherichia coli (E. coli) (MIC = 7.93 ± 0.17 μg mL-1) bacteria. The antibacterial mechanism of CDs-C9 is ascribed to the balance between the positive charge and hydrophobicity of the alkyl chains. TAA moieties are responsible for enhanced adherence on the bacterial cell membrane, its penetration and disturbance of physiological metabolism. CDs-C9 were not effective in the generation of reactive oxygen species excluding the oxidative damage mechanism. In addition, CDs-C9 effectively promoted the antibiofilm treatment of S. aureus and E. coli biofilms outperforming previously-reported CDs in terms of treatment duration and minimal inhibitory concentration. The good biocompatibility of CDs-C9 was demonstrated on mouse fibroblast (NIH/3T3), HeLa and U-87 MG cell lines for concentrations up to 256 μg mL-1. Collectively, our work highlights the correlation between the surface chemistry of CDs and their antimicrobial performance.
- MeSH
- antibakteriální látky * farmakologie MeSH
- Escherichia coli MeSH
- gramnegativní bakterie MeSH
- grampozitivní bakterie metabolismus MeSH
- myši MeSH
- stafylokokové infekce * MeSH
- Staphylococcus aureus MeSH
- uhlík chemie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The present research was undertaken to develop a chitosan-collagen film for controlled delivery of combinations of local anesthetics. The film has been prepared by casting which is a versatile, rapid and low-cost approach distinguished by high reproducibility. The mechanical, morphological, and physicochemical properties of the films and the impact of the drug loading were evaluated. We showed that the formulations have a good combination of strength and flexibility with high water permeability. Surface morphology investigation indicates a variation in roughness depending on the loaded compound. Release studies were performed in controlled environments and the data processed by the Higuchi model to assess the dynamics of the release. The local anesthetics, lidocaine, tetracaine, and benzocaine, were uniformly distributed within the matrix and released in a rate and magnitude specific for the drug concentration and combination tunable in a range time from 6 h to 24 h. The films dissolve completely in the physiological environment within 24 h without leaving any toxic metabolites as both of the components are recognized as safe. In vitro cytotoxicity and cell proliferation tests performed on human dermal fibroblast demonstrate the biocompatibility and lack of cytotoxicity of the prepared formulations.
- MeSH
- anestetika lokální aplikace a dávkování MeSH
- benzokain aplikace a dávkování MeSH
- buněčná smrt účinky léků MeSH
- chitosan chemie MeSH
- difuze MeSH
- fibroblasty cytologie účinky léků MeSH
- kinetika MeSH
- kolagen chemie MeSH
- koncentrace vodíkových iontů MeSH
- léky s prodlouženým účinkem aplikace a dávkování MeSH
- lidé MeSH
- lidokain aplikace a dávkování MeSH
- molekulová hmotnost MeSH
- pára MeSH
- permeabilita MeSH
- povrchové vlastnosti MeSH
- proliferace buněk účinky léků MeSH
- skot MeSH
- systémy cílené aplikace léků * MeSH
- tetrakain aplikace a dávkování MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The work is focused on the development of microspheres based on the combination of two polysaccharides; chitosan and alginic acid with the aim to allocate, hold, release and protect environmentally sensible molecules. The microspheres were prepared using a solvent-free, low cost and scalable approach and two enzymes; trypsin and protease from Aspergillus Oryzae have been used as a model to evaluate the microspheres peculiarities. The proteins were encapsulated during the microspheres preparation. The relationship between the polysaccharides weight ratio and the morphology, stability and ability of the carrier to allocate the enzymes has been evaluated. The enzymatic activity and the release kinetics were assessed in different conditions to assess the impact of the external environment. Obtained results demonstrate the efficacy of the prepared microspheres to preserve the activity of relevant bioactive compounds which are highly relevant in food, cosmetic and pharmaceutic, but the application is limited due to their high sensibility.
- MeSH
- Aspergillus oryzae enzymologie MeSH
- buňky NIH 3T3 MeSH
- chitosan chemie toxicita MeSH
- enzymy imobilizované chemie metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- kyselina alginová chemie toxicita MeSH
- lidé MeSH
- mikrosféry * MeSH
- myši MeSH
- testování materiálů MeSH
- tobolky MeSH
- trypsin chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
β-carotene is a natural compound with significant antioxidant activity. However, its poor solubility in water and low stability reduce its potential application. Innovative polyplexes based on the combination of amphiphilic chitosan assembled with DNA have been developed using a solvent-free, simple and low-cost method with the aim to load, retain and enhance the antioxidant capability of β-carotene. The polyplexes, with dimension about 100 nm, and excellent stability, were able to hold up to 400 μg of β-carotene per mg of the carrier, with minimal loss till two weeks. The antioxidant activity was significantly enhanced after loading, as demonstrated using two well known methods. Cytotoxicity assay confirmed the not toxicity of the system. The results suggest the polyplexes as an excellent candidate to develop formulation able to preserve and enhance the peculiarities of compounds which are used mainly in food, cosmetic and pharmaceutic but with still some limitations.
- MeSH
- antioxidancia chemie farmakologie toxicita MeSH
- beta-karoten chemie farmakologie toxicita MeSH
- bifenylové sloučeniny chemie MeSH
- buňky NIH 3T3 MeSH
- chitosan chemie MeSH
- DNA chemie MeSH
- hydrofobní a hydrofilní interakce * MeSH
- myši MeSH
- pikráty chemie MeSH
- rozpustnost MeSH
- stabilita léku MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
An innovative microcarrier based on a carboxy-enriched and branched polylactic acid derivative was developed to enhance the in vitro phototoxicity of the photosensitizer and prodrug 5-aminolevulinic. Microparticles, prepared by double emulsion technique and loaded with the prodrug were carefully characterized and the effect of the polymer structure on the chemical, physical and biological properties of the final product was evaluated. Results showed that microparticles have a spherical shape and ability to allocate up to 30 μg of the photosensitizer per mg of carrier despite their difference in solubility. Release studies performed in various simulated physiological conditions demonstrate the influence of the branched structure and the presence of the additional carboxylic groups on the release rate and the possibility to modulate it. In vitro assays conducted on human epithelial adenocarcinoma cells proved the not cytotoxicity of the carriers in a wide range of concentrations. The hemocompatibility and surface proteins adsorption were evaluated at different microparticles concentrations to evaluate the safety and estimate the possible microparticles residential time in the bloodstream. The advantages, of loading 5-aminolevulinic acid in the prepared carrier has been deeply described in terms of enhanced phototoxicity, compared to the free 5-aminolevulinic acid formulation after irradiation with light at 635 nm. The obtained results demonstrate the advantages of the prepared derivative compared to the linear polylactide for future application in photodynamic therapy based on the photosensitizer 5-aminolevulinic acid.
- MeSH
- erytrocyty cytologie účinky léků metabolismus MeSH
- fotosenzibilizující látky chemie toxicita MeSH
- HeLa buňky MeSH
- hemolýza účinky léků MeSH
- koncentrace vodíkových iontů MeSH
- kyselina aminolevulová chemie metabolismus toxicita MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemie MeSH
- polyestery chemie MeSH
- rozpustnost MeSH
- světlo MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Polysaccharides based nanocomplexes have been developed for encapsulation, controlled delivery and to enhance the phototoxicity of the photosensitizer 5-aminolevulinic acid for application in photodynamic therapy. The nanocomplexes were prepared by coacervation in a solvent free environment using chitosan as polycation while alginic and polygalacturonic acid as polyanions. The complexes showed average dimension in the range 90-120nm, good stability in simulated physiological media and high drug encapsulation efficiency, up to 800μg per mg of carrier. Release studies demonstrate the possibility to tune the overall release rate and the intensity of the initial burst by changing the external pH. Cytotoxicity and photocytotoxicity tests confirmed the not toxicity of the used polysaccharides. Cell viability results confirmed the improvement of 5-aminolevulinic acid phototoxicity when loaded into the carrier compared to the free form. No effect of the irradiation on the nanocomplexes structure and on the release kinetics of the drug was observed. The results demonstrate that the prepared formulations have suitable properties for future application in photodynamic therapy and to ameliorate the therapeutic efficacy and overcome the side-effects related to the use of the photosensitizer 5-aminolevulinic acid.
- MeSH
- chitosan chemie MeSH
- fotosenzibilizující látky chemie toxicita MeSH
- HeLa buňky MeSH
- koncentrace vodíkových iontů MeSH
- kyselina aminolevulová chemie toxicita MeSH
- lidé MeSH
- nanočástice chemie MeSH
- nosiče léků chemie MeSH
- světlo MeSH
- teplota MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- viabilita buněk účinky léků účinky záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The use of organic-inorganic hybrid nanocarriers for controlled release of anticancer drugs has been gained a great interest, in particular, to improve the selectivity and efficacy of the drugs. In this study, iron oxide nanoparticles were prepared then surface modified via diazonium chemistry and coated with chitosan, and its derivative chitosan-grafted polylactic acid. The purpose was to increase the stability of the nanoparticles in physiological solution, heighten drug-loading capacity, prolong the release, reduce the initial burst effect and improve in vitro cytotoxicity of the model drug doxorubicin. The materials were characterized by DLS, ζ-potential, SEM, TGA, magnetization curves and release kinetics studies. Results confirmed the spherical shape, the presence of the coat and the advantages of using chitosan, particularly its amphiphilic derivative, as a coating agent, thereby surpassing the qualities of simple iron oxide nanoparticles. The coated nanoparticles exhibited great stability and high encapsulation efficiency for doxorubicin, at over 500μg per mg of carrier. Moreover, the intensity of the initial burst was clearly diminished after coating, hence represents an advantage of using the hybrid system over simple iron oxide nanoparticles. Cytotoxicity studies demonstrate the increase in cytotoxicity of doxorubicin when loaded in nanoparticles, indirectly proving the role played by the carrier and its surface properties in cell uptake.
- MeSH
- antitumorózní látky aplikace a dávkování MeSH
- chitosan chemie MeSH
- doxorubicin aplikace a dávkování MeSH
- HeLa buňky MeSH
- lidé MeSH
- nanočástice chemie MeSH
- nosiče léků chemie MeSH
- povrchové vlastnosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method. The structure of the SPLA was characterized by1H NMR, while the product CS-SPLA was analyzed by FTIR-ATR to prove the occurrence of the reaction. Results showed that the diameters and ζ-potential of the nanocomplexes fall in the range 120-200nm and 20-37mV, respectively. SEM and TEM analysis confirmed the spherical shape and dimensions of the nanocomplexes. The presence of hydrophobic side chain SPLA did not influence the encapsulation efficiency of the drugs but strongly reduced the initial burst and prolonged release over time compared to unmodified chitosan. MS analysis showed that no degradation or interactions between the drugs and carrier were exhibited after loading or 24h of release had taken place, confirming the protective role of the nanocomplexes. In vitro tests demonstrated an increase in the cytotoxicity of the drugs when loaded in the prepared carriers.
- MeSH
- buňky NIH 3T3 MeSH
- chitosan chemie toxicita MeSH
- doxorubicin chemie MeSH
- fluorouracil chemie MeSH
- léky s prodlouženým účinkem MeSH
- myši MeSH
- nanostruktury chemie toxicita MeSH
- nosiče léků chemie MeSH
- polyestery chemie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Polysaccharide-based nanocomplexes, intended for simultaneous encapsulation and controlled release of 5-Fluorouracil (5-FU) and Temozolomide (TMZ) were developed via the complexation method using chitosan, alginic and polygalacturonic acid. Investigation focused on the influence of polysaccharides on the properties of the system and amelioration of the stability of the drugs, in particular TMZ. The dimensions of particles and their ζ-potential were found to range between 100 and 200nm and -25 to +40mV, respectively. Encapsulation efficiency varied from 16% to over 70%, depending on the given system. The influence of pH on the release and co-release of TMZ and 5-FU was evaluated under different pH conditions. The stability of the loaded drug, in particular TMZ, after release was evaluated and confirmed by LC-MS analysis. Results suggested that the amount of loaded drug(s) and the release rate is connected with the weight ratio of polysaccharides and the pH of the media. One-way ANOVA analysis on the obtained data revealed no interference between the drugs during the encapsulation and release process, and in particular no hydrolysis of TMZ occurred suggesting that CS-ALG and CS-PGA would represent interesting carriers for multi-drug controlled release and drugs protection.
- MeSH
- algináty chemie MeSH
- antimetabolity antitumorózní chemie MeSH
- antitumorózní látky alkylující chemie MeSH
- chitosan chemie MeSH
- dakarbazin analogy a deriváty chemie MeSH
- fixní kombinace léků MeSH
- fluorouracil chemie MeSH
- kyselina glukuronová chemie MeSH
- kyseliny hexuronové chemie MeSH
- léky s prodlouženým účinkem chemie MeSH
- nanočástice chemie MeSH
- nosiče léků chemie MeSH
- pektiny chemie MeSH
- prekurzory léčiv chemie MeSH
- příprava léků MeSH
- stabilita léku MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
Chitosan and chitosan-grafted polylactic acid as a matrix for BSA encapsulation in a nanoparticle structure were prepared through a polyelectrolyte complexation method with dextran sulfate. Polylactic acid was synthetized via a polycondensation reaction using the non-metal-based initiator methanesulfonic acid and grafted to the chitosan backbone by a coupling reaction, with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as the condensing agent. The effect of concentration of the polymer matrix utilized herein on particle diameter, ζ-potential, encapsulation efficiency, and the release kinetic of the model protein bovine serum albumin at differing pH levels was investigated. The influence of pH and ionic strength on the behavior of the nanoparticles prepared was also researched. Results showed that grafting polylactic acid to chitosan chains reduced the initial burst effect in the kinetics of BSA release from the structure of the nanoparticles. Furthermore, a rise in encapsulation efficiency of the bovine serum albumin and diminishment in nanoparticle diameter were observed due to chitosan modification. The results suggest that both polymers actually show appreciable encapsulation efficiency; and release rate of BSA. CS-g-PLA is more suitable than unmodified CS as a carrier for controlled protein delivery.
- MeSH
- chitosan chemie MeSH
- koncentrace vodíkových iontů MeSH
- kyselina mléčná chemie MeSH
- léky s prodlouženým účinkem MeSH
- molekulová hmotnost MeSH
- nanočástice chemie MeSH
- polymery chemie MeSH
- rozpustnost MeSH
- sérový albumin hovězí chemie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
