Enhancement of temozolomide stability by loading in chitosan-carboxylated polylactide-based nanoparticles

In the presented work, amphiphilic nanoparticles based on chitosan and carboxy-enriched polylactic acid have been prepared to improve the stability of the pro-drug temozolomide in physiological media by encapsulation. The carrier, with a diameter in the range of 150–180 nm, was able to accommodate up to 800 μg of temozolomide per mg of polymer. The obtained formulation showed good stability in physiological condition and preparation media up to 1 month. Temozolomide loaded inside the carrier exhibited greater stability than the free drug, in particular in simulated physiological solution at pH 7.4 where the hydrolysis in the inactive metabolite was clearly delayed. CS-SPLA nanoparticles demonstrated a pH-dependent TMZ release kinetics with the opportunity to increase or decrease the rate. Mass spectroscopy, UV-Vis analysis, and in vitro cell tests confirmed the improvement in temozolomide stability and effectiveness when loaded into the polymeric carrier, in comparison with the free drug. © 2017, The Author(s).15-08287Y, GACR, Grantová Agentura České Republiky; 15-08287Y, GAČR, Grantová Agentura České Republiky; CZ.1.05/2.1.00/19.0409, MŠMT, Ministerstvo Školství, Mládeže a Tělovýchovy; LO1504, MŠMT, Ministerstvo Školství, Mládeže a TělovýchovyCzech Science Foundation [15-08287Y]; Ministry of Education, Youth and Sports of the Czech Republic [LO1504, CZ.1.05/2.1.00/19.0409]; Internal Grant Agency of the Tomas Bata University in Zlin [IGA/CPS/2016/004

Effect of iron-oxide nanoparticles impregnated bacterial cellulose on overall properties of alginate/casein hydrogels: Potential injectable biomaterial for wound healing applications

In this study we report the preparation of novel multicomponent hydrogels as potential biomaterials for injectable hydrogels comprised of alginate, casein and bacterial cellulose impregnated with iron nanoparticles (BCF). These hydrogels demonstrated amide cross-linking of alginate–casein, ionic cross-linking of alginate and supramolecular interaction due to incorporation of BCF. Incorporation of BCF into the hydrogels based on natural biopolymers was done to reinforce the hydrogels and impart magnetic properties critical for targeted drug delivery. This study aimed to improve overall properties of alginate/casein hydrogels by varying the BCF loading. The physico-chemical properties of gels were characterized via FTIR, XRD, DSC, TGA, VSM and mechanical compression. In addition, swelling, drug release, antibacterial activity and cytotoxicity studies were also conducted on these hydrogels. The results indicated that incorporation of BCF in alginate/casein hydrogels led to mechanically stronger gels with magnetic properties, increased porosity and hence increased swelling. A porous structure, which is essential for migration of cells and biomolecule transportation, was confirmed from microscopic analysis. The porous internal structure promoted cell viability, which was confirmed through MTT assay of fibroblasts. Moreover, a hydrogel can be useful for the delivery of essential drugs or biomolecules in a sustained manner for longer durations. These hydrogels are porous, cell viable and possess mechanical properties that match closely to the native tissue. Collectively, these hybrid alginate–casein hydrogels laden with BCF can be fabricated by a facile approach for potential wound healing applications. © MDPI AG. All rights reserved.Technology Agency of the Czech Republic (TACR)-M-ERA.NET [TH71020005]; Ministry of Education, Youth and Sports of the Czech Republic-DKRVO [RP/CPS/2020/005

Exploring the critical factors limiting polyaniline biocompatibility

Today, the application of polyaniline in biomedicine is widely discussed. However, information about impurities released from polyaniline and about the cytotoxicity of its precursors aniline, aniline hydrochloride, and ammonium persulfate are scarce. Therefore, cytotoxicity thresholds for the individual precursors and their combinations were determined (MTT assay) and the type of cell death caused by exposition to the precursors was identified using flow-cytometry. Tests on fibroblasts revealed higher cytotoxicity of ammonium persulfate than aniline hydrochloride. Thanks to the synergic effect, both monomers in combination enhanced their cytotoxicities compared with individual substances. Thereafter, cytotoxicity of polyaniline doped with different acids (sulfuric, nitric, phosphoric, hydrochloric, and methanesulfonic) was determined and correlated with impurities present in respective sample (HPLC). The lowest cytotoxicity showed polyaniline doped with phosphoric acid (followed by sulfuric, methanesulfonic, and nitric acid). Cytotoxicity of polyaniline was mainly attributed to the presence of residual ammonium persulfate and low-molecular-weight polar substances. This is crucial information with respect to the purification of polyaniline and production of its cytocompatible form.Ministry of Education, Youth and Sports of the Czech Republic [LO1504]; Czech Science Foundation [17-05095S]; Tomas Bata University in Zlin [IGA/CPS/2019/004

In-vitro hemocompatibility of polyaniline functionalized by bioactive molecules

Hemocompatibility is an essential prerequisite for the application of materials in the field of biomedicine and biosensing. In addition, mixed ionic and electronic conductivity of conducting polymers is an advantageous property for these applications. Heparin-like materials containing sulfate, sulfamic, and carboxylic groups may have an anticoagulation effect. Therefore, sodium dodecylbenzenesulfonate, 2-aminoethane-1-sulfonic acid andN-(2-acetamido)-2-aminoethanesulfonic acid were used for modification of the representative of conducting polymers, polyaniline, and the resulting products were studied in the context of interactions with human blood. The anticoagulation activity was then correlated to surface energy and conductivity of the materials. Results show that anticoagulation activity is highly affected by the presence of suitable functional groups originating from the used heparin-like substances, and by the properties of polyaniline polymer itself. © 2019 by the authors.Czech Science FoundationGrant Agency of the Czech Republic [19-16861S]; Ministry of Education, Youth and Sports of the Czech Republic (NPU I) [LO1504]; TBU in Zlin [IGA/CPS/2019/004]; Slovenian Research AgencySlovenian Research Agency - Slovenia [P2-0082

Adhesion, proliferation and migration of NIH/3T3 cells on modified polyaniline surfaces

Polyaniline shows great potential and promises wide application in the biomedical field thanks to its intrinsic conductivity and material properties, which closely resemble natural tissues. Surface properties are crucial, as these predetermine any interaction with biological fluids, proteins and cells. An advantage of polyaniline is the simple modification of its surface, e.g., by using various dopant acids. An investigation was made into the adhesion, proliferation and migration of mouse embryonic fibroblasts on pristine polyaniline films and films doped with sulfamic and phosphotungstic acids. In addition, polyaniline films supplemented with poly (2-acrylamido-2-methyl-1-propanesulfonic) acid at various ratios were tested. Results showed that the NIH/3T3 cell line was able to adhere, proliferate and migrate on the pristine polyaniline films as well as those films doped with sulfamic and phosphotungstic acids; thus, utilization of said forms in biomedicine appears promising. Nevertheless, incorporating poly (2-acrylamido-2-methyl-1-propanesulfonic) acid altered the surface properties of the polyaniline films and significantly affected cell behavior. In order to reveal the crucial factor influencing the surface/cell interaction, cell behavior is discussed in the context of the surface energy of individual samples. It was clearly demonstrated that the lesser the difference between the surface energy of the sample and cell, the more cyto-compatible the surface is. © 2016 by the authors; licensee MDPI, Basel, Switzerland.Ministry of Education, Youth and Sports of the Czech Republic, Program NPU I [LO1504

Self-crosslinked chitosan/dialdehyde xanthan gum blended hypromellose hydrogel for the controlled delivery of ampicillin, minocycline and rifampicin

The design of improved biopolymeric based hydrogel materials with high load-capacity to serve as biocompatible drug carriers is a challenging task with vital implications in health sciences. In this work, chitosan crosslinked dialdehyde xanthan gum interpenetrated hydroxypropyl methylcellulose gels were developed for the controlled delivery of different antibiotic drugs including ampicillin, minocycline and rifampicin. The prepared hydrogel scaffolds were characterized by rheology method, FTIR, SEM, TGA and compression analysis. In addition, gelation kinetics, swelling, in vitro degradation and drug release rate were studied under simulated gastrointestinal fluid conditions of pH 2.0 and 7.4 at 37 °C. Results demonstrated the gel composition and structure affected drug release kinetics. The release study showed more than 50% cumulative release within 24 h for all investigated antibiotic drugs. In vitro cell cytocompatibility using mouse embryonic fibroblast cell lines depicted ≥80% cell viability, indicating the gels are non-toxic. Finally, the antibacterial activity of loaded gels was evaluated against Gram-negative and positive bacteria (Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia), which correlated well with swelling and drug release results. Overall, the present study demonstrated that the produced hydrogel scaffolds serves as promising material for controlled antibiotic delivery towards microbial growth inhibition. © 2020 Elsevier B.V.Tomas Bata University in Zlin; Ministry of Education, Youth & Sports of the Czech Republic - DKRVO [RP/CPS/2020/005

Formulation of magneto-responsive hydrogels from dually cross-linked polysaccharides: Synthesis, tuning and evaluation of rheological properties

Smart hydrogels based on natural polymers present an opportunity to fabricate responsive scaffolds that provide an immediate and reversible reaction to a given stimulus. Modulation of mechanical characteristics is especially interesting in myocyte cultivation, and can be achieved by magnetically controlled stiffening. Here, hyaluronan hydrogels with carbonyl iron particles as a magnetic filler are prepared in a low-toxicity process. Desired mechanical behaviour is achieved using a combination of two cross-linking routes-dynamic Schiff base linkages and ionic cross-linking. We found that gelation time is greatly affected by polymer chain conformation. This factor can surpass the influence of the number of reactive sites, shortening gelation from 5 h to 20 min. Ionic cross-linking efficiency increased with the number of carboxyl groups and led to the storage modulus reaching 10(3) Pa compared to 10(1) Pa-10(2) Pa for gels cross-linked with only Schiff bases. Furthermore, the ability of magnetic particles to induce significant stiffening of the hydrogel through the magnetorheological effect is confirmed, as a 10(3)-times higher storage modulus is achieved in an external magnetic field of 842 kA.m(-1). Finally, cytotoxicity testing confirms the ability to produce hydrogels that provide over 75% relative cell viability. Therefore, dual cross-linked hyaluronan-based magneto-responsive hydrogels present a potential material for on-demand mechanically tunable scaffolds usable in myocyte cultivation.project OP RDE Junior Grants of TBU in Zlin [CZ.02.2.69/0.0/0.0/19_073/0016941]; TBU in Zlin [IGA/CPS/2022/001]; Ministry of Education, Youth and Sports of the Czech Republic-DKRVO [RP/CPS/2022/003]; Ministry of Education, Youth and Sports of the Czech Republic project-DKRVO [RP/CPS/2022/001

Plasma mediated chlorhexidine immobilization onto polylactic acid surface via carbodiimide chemistry: Antibacterial and cytocompatibility assessment

The development of antibacterial materials has great importance in avoiding bacterial contamination and the risk of infection for implantable biomaterials. An antibacterial thin film coating on the surface via chemical bonding is a promising technique to keep native bulk material properties unchanged. However, most of the polymeric materials are chemically inert and highly hydrophobic, which makes chemical agent coating challenging Herein, immobilization of chlorhexidine, a broad-spectrum bactericidal cationic compound, onto the polylactic acid surface was performed in a multistep physicochemical method. Direct current plasma was used for surface functionalization, followed by carbodiimide chemistry to link the coupling reagents of N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and N-Hydroxysuccinimide (NHs) to create a free bonding site to anchor the chlorhexidine. Surface characterizations were performed by water contact angle test, X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM). X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM). The antibacterial activity was tested using Staphylococcus aureus and Escherichia coli. Finally, in vitro cytocompatibility of the samples was studied using primary mouse embryonic fibroblast cells. It was found that all samples were cytocompatible and the best antibacterial performance observed was the Chlorhexidine immobilized sample after NHs activation. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Czech Science FoundationGrant Agency of the Czech Republic [19-16861S]; Ministry of Education, Youth and Sports of the Czech Republic-DKRVO [RP/CPS/2020/001]; DKRVO [RP/CPS/2020/005]; Slovenian Research AgencySlovenian Research Agency - Slovenia [L2-2616]RP/CPS/2020/005; Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT: RP/CPS/2020/001; Grantová Agentura České Republiky, GA ČR: 19-16861S; Javna Agencija za Raziskovalno Dejavnost RS, ARRS: L2-261

Behaviour of titanium dioxide particles in artificial body fluids and human blood plasma

The growing application of materials containing TiO2 particles has led to an increased risk of human exposure, while a gap in knowledge about the possible adverse effects of TiO2 still exists. In this work, TiO2 particles of rutile, anatase, and their commercial mixture were exposed to various environments, including simulated gastric fluids and human blood plasma (both representing in vivo conditions), and media used in in vitro experiments. Simulated body fluids of different com-positions, ionic strengths, and pH were used, and the impact of the absence or presence of chosen enzymes was investigated. The physicochemical properties and agglomeration of TiO2 in these media were determined. The time dependent agglomeration of TiO2 related to the type of TiO2, and mainly to the type and composition of the environment that was observed. The presence of enzymes either prevented or promoted TiO2 agglomeration. TiO2 was also observed to exhibit concentration-dependent cytotoxicity. This knowledge about TiO2 behavior in all the abovementioned environments is critical when TiO2 safety is considered, especially with respect to the significant impact of the presence of proteins and size‐related cytotoxicity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Czech Science FoundationGrant Agency of the Czech Republic [20-28732S]; Ministry of Education, Youth and Sports of the Czech Republic-grant DKRVO [RP/CPS/2020/001]; TBU in Zlin [IGA/CPS/2021/001]Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT: IGA/CPS/2021/001, RP/CPS/2020/001; Grantová Agentura České Republiky, GA ČR: 28732

Enhancing cisplatin anticancer effectivity and migrastatic potential by modulation of molecular weight of oxidized dextran carrier

The molecular weight (Mw) of dextran derivatives, such as regioselectively oxidized dicarboxydextran (DXA), is greatly influencing their faith in an organism, which could be possibly used to improve anticancer drug delivery. Here we present a modified method of sulfonation-induced chain scission allowing direct and accurate control over the Mw of DXA without increasing its polydispersity. Prepared DXA derivatives (Mw = 10–185 kDa) have been conjugated to cisplatin and the Mw of the carrier found to have a significant impact on cisplatin release rates, in vitro cytotoxicity, and migrastatic potential. Conjugates with the high-Mw DXA showed particularly increased anticancer efficacy. The best conjugate was four times more effective against malignant prostatic cell lines than free cisplatin and significantly inhibited the ovarian cancer cell migration. This was traced to the characteristics of spontaneously formed cisplatin-crosslinked DXA nanogels influenced by Mw of DXA and amount of loaded cisplatin. © 2021 Elsevier LtdMinistry of Education, Youth, and Sports of the Czech Republic -DKRVO [RP/CPS/2020/006]; Ministry of Education, Youth and Sports of the Czech RepublicMinistry of Education, Youth & Sports - Czech Republic [CZ.02.1.01/0.0/0.0/15_003/0000444, MUNI/A/1698/2020, MUNI/A/1246/2020, LM2018127]; Masaryk University in Brno [InGA/SUP/08/2020]; Czech Science FoundationGrant Agency of the Czech Republic [19-16861S]; Charles University in Prague [Progress Q26/LF1, Q27/LF1]RP/CPS/2020/006; Univerzita Karlova v Praze, UK: Q27/LF1; Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT: CZ.02.1.01/0.0/0.0/15_003/0000444, InGA/SUP/08/2020, MUNI/A/1246/2020, MUNI/A/1698/2020; Grantová Agentura České Republiky, GA ČR: 19-16861S, LM201812