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

Comparison of dialdehyde polysaccharides as crosslinkers for hydrogels: The case of poly(vinyl alcohol)

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. © 2021 Elsevier LtdRP/CPS/2020/006; Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT; Grantová Agentura České Republiky, GA ČR: 19-16861S; Univerzita Tomáše Bati ve Zlíně: IGA/CPS/2021/002Ministry of Education, Youth and Sports of the Czech Republic - DKRVO [RP/CPS/2020/006]; Tomas Bata University in Zlin [IGA/CPS/2021/002]; Czech Science FoundationGrant Agency of the Czech Republic [19-16861S

Design of dialdehyde cellulose crosslinked poly(vinyl alcohol) hydrogels for transdermal drug delivery and wound dressings

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. © 2020 Elsevier B.V.Ministry of Education, Youth and Sports of the Czech Republic Program NPU I [LO1504]; Tomas Bata University in Zlin [IGA/CPS/2020/003

Pycnogenol and DNA Damage and Repair in Elderly How Does Pycnogenol ® Influence Oxidative Damage to DNA and Its Repair Ability in Elderly People? 264)

Abstract: Our purpose in this randomized, double blind, placebo controlled study was to find out the possible effect of a polyphenolic pine bark extract, Pycnogenol ® (Pyc) on the level of 8-oxo-7,8-dihydroguanine (8-oxoG) as representative of oxidative damage to DNA and on the DNA repair ability of elderly people. According to our results, three months of Pyc administration had no effect on the level of oxidative damage to DNA or on repair ability, but we found a relationship between the level of 8-oxoG and repair ability of DNA in this group. To conclude, even if the positive effect of Pyc was not confirmed in the case of elderly people it is important to highlight the necessity of further investigations about the mechanisms of Pyc acting on different age groups

Highly efficient affinity anchoring of gold nanoparticles on chitosan nanofibers via dialdehyde cellulose for reusable catalytic devices

Polysaccharides are often utilized as reducing and stabilizing agents and as support in the synthesis of gold nanoparticles (AuNPs). However, using approaches like spin coating or dip coating, AuNPs are generally bound to the support only by weak interactions, which can lead to decreased stability of the composite. Here, a two-stage approach for the preparation of composites with covalently anchored AuNPs is proposed. First, 5 nm AuNPs with high catalytic activity for the reduction of 4-nitrophenol (TOF = 15.8 min−1) were synthesized and stabilized using fully oxidized and solubilized 2,3-dialdehyde cellulose (DAC). Next, the carbonyl groups in the shell of prepared nanoparticles were used to tether AuNPs to chitosan nanofibers with quantitative efficacy in a process that we termed “affinity anchoring”. Schiff bases formed during this process were subsequently reduced to secondary amines by borohydride, which greatly improved the stability of the composite in the broad pH range from 3 to 9. The catalytic efficacy of the resulting composite is demonstrated using a model catalytic device, showing high stability, fast conversion rates, and direct reusability. © 2023 Elsevier LtdDKRVO, (RP/CPS/2022/007); Tomas Bata University in Zlin, TBU, (IGA/CPS/2023/006); Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT; Grantová Agentura České Republiky, GA ČR, (23-07361S); Masarykova Univerzita, MU, (MUNI/A/1298/2022

Oxidized polysaccharides for anticancer-drug delivery: What is the role of structure?

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. © 2021 Elsevier LtdMinistry of Education, Youth and Sports of the Czech Republic - DKRVO [RP/CPS/2020/006]; project Advanced Functional Nanorobots [CZ.02.1.01/0.0/0.0/15_003/0000444]; internal grant for specific research from TBU in Zlin [IGA/CPS/2020/003]; Faculty of Medicine MU Brno; Ministry of Education, Youth and Sports of the Czech RepublicMinistry of Education, Youth & Sports - Czech Republic [LM2018127]; project "e-Infrastruktura CZ" (e-INFRA) within the program Projects of Large Research, Development and Innovations Infrastructures [LM2018140]CZ.02.1.01/0.0/0.0/15_003/0000444, RP/CPS/2020/006; LM2018127; IGA/CPS/2020/003; Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT: LM201814

Chitosan/dialdehyde cellulose hydrogels with covalently anchored polypyrrole: Novel conductive, antibacterial, antioxidant, immunomodulatory, and anti-inflammatory materials

In this work, conductive composite hydrogels with covalently attached polypyrrole (PPy) nanoparticles are prepared. Hydrogels are based on partially re-acetylated chitosan soluble at physiological pH without any artificial structural modifications or need for an acidic environment, which simplifies synthesis and purification. Low-toxic and sustainable dialdehyde cellulose (DAC) was used for crosslinking chitosan and covalent anchoring of PPy colloidal particles. The condensation reaction between DAC and PPy is reported for the first time and improves not only the anchoring of PPy particles but also control over the properties of the final composite. The soluble chitosan and PPy particles are shown to act in synergy, which improves the biological properties of the materials. Prepared composite hydrogels are non-cytotoxic, non-irritating, antibacterial, can capture reactive oxygen species often related to excessive inflammation, have conductivity similar to human tissues, enhance in vitro cell growth (migration assay), and have immunomodulatory effects related to the stimulation of neutrophils and macrophages. The covalent attachment of PPy also strengthens the hydrogel network. The aldol condensation as a method for PPy covalent anchoring thus presents an interesting possibility for the development of advanced biomaterials in the future.DKRVO, (RP/CPS/2022/001, RP/CPS/2022/007); Tomas Bata University in Zlín, TBU, (IGA/CPS/2023/001); Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT; Grantová Agentura České Republiky, GA ČR, (23-07425S)Ministry of Education, Youth and Sports of the Czech Republic [RP/CPS/2022/001]; DKRVO [RP/CPS/2022/007]; Internal Grants of Tomas Bata University in Zlin [IGA/CPS/2023/001]; Czech Science Foundation [23-07425S

Establishing the background level of base oxidation in human lymphocyte DNA: results of an interlaboratory validation study

SCOPUS: ar.jinfo:eu-repo/semantics/publishe