Thiolated polymers: Bioinspired polymers utilizing one of the most important bridging structures in nature

Leichner, Christina; Jelkmann, Max; Bernkop‐Schnürch, Andreas

doi:10.1016/j.addr.2019.04.007

Cited by 102 publications

(106 citation statements)

References 387 publications

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“…In addition, without deeper interpenetration, thiomers will not be able to interact with membrane-bound substructures of epithelial cells providing additional effects such as an opening of tight junctions [ 15 ]. Even in the case of in-situ gelling properties, too high reactivity of preactivated thiomers might be disadvantageous, as a gelation that is too fast can limit a proper distribution of the polymer over the target tissue [ 16 ]. According to these considerations, moderate reactive s -protected thiomers might provide higher mucoadhesive properties.…”

Section: Introductionmentioning

confidence: 99%

Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems

et al. 2020

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As less reactive s-protected thiomers can likely interpenetrate the mucus gel layer to a higher extent before getting immobilized via disulfide bond formation with mucins, it was the aim of this study to develop a novel type of s-protected thiomer based on the less reactive substructure cysteine-N-acetyl cysteine (Cys-NAC) in order to obtain improved mucoadhesive properties. For this purpose, two types of s-protected thiomers, polyacrylic acid-cysteine-mercaptonicotinic acid (PAA-Cys-MNA) and polyacrylic acid-cysteine-N-acetyl cysteine (PAA-Cys-NAC), were synthesized and characterized by Fourier-transform infrared spectroscopy (FT-IR) and the quantification of attached disulfide ligands. The viscosity of both products was measured in the presence of NAC and mucus. Both thiomers were also evaluated regarding swelling behavior, tensile studies and retention time on the porcine intestinal mucosa. The FT-IR spectra confirmed the successful attachment of Cys-MNA and Cys-NAC ligands to PAA. The number of attached sulfhydryl groups was in the range of 660–683 µmol/g. The viscosity of both s-protected thiomers increased due to the addition of increasing amounts of NAC. The viscosity of the mucus increased in the presence of 1% PAA-Cys-MNA and PAA-Cys-NAC 5.6- and 10.9-fold, respectively, in comparison to only 1% PAA. Both s-protected thiomers showed higher water uptake than unmodified PAA. The maximum detachment force (MDF) and the total work of adhesion (TWA) increased in the case of PAA-Cys-MNA up to 1.4- and 1.6-fold and up to 2.4- and 2.8-fold in the case of PAA-Cys-NAC. The retention of PAA, PAA-Cys-MNA, and PAA-Cys-NAC on porcine intestinal mucosa was 25%, 49%, and 76% within 3 h, respectively. The results of this study provide evidence that less reactive s-protected thiomers exhibit higher mucoadhesive properties than highly reactive s-protected thiomers.

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Section: Introductionmentioning

confidence: 99%

Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems

et al. 2020

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“…However, other non‐interacting polymers such as poly(2‐alkyl‐2‐oxazolines) and poly(vinyl alcohol) have also been considered . Further examples include particles modified with zeta‐potential shifting polymers, as well as formulations equipped with mucolytic enzymes or thiol groups, self‐emulsifying drug delivery systems, and densely‐charged particles that have an overall neutral net charge (sometimes referred to as virus‐mimicking particles) . The latter concept is a nature‐inspired approach, where the aim is to mimic mucopenetrating viruses that have a high surface charge density but overall neutral net‐charge due to a balanced distribution of positive and negative charges, minimizing the affinity to mucus components and enables the viruses to cross the mucus almost unhindered …”

Section: Methodsmentioning

confidence: 99%

Mucopenetrating Zwitterionic Micelles

2020

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The intestinal mucus layer remains a challenging biological barrier to cross for nanoformulations. We report the assembly of zwitterionic micelles with 2-methacryloyloxyethyl phosphorylcholine as the zwitterionic entity in the corona-forming part of the amphiphilic block copolymers. These ca. 200 nm micelles do not have inherent cytotoxicity in Caco-2 cells for a 24 h incubation time. The time-resolved crossing of the mucus layer in Caco-2/HT29-MTX-E12 cocultures of these spherical micelles with narrow polydispersity is shown.[a] Dr.

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“…It is known that thiolated chitosan derivatives have a high mucoadhesivity thanks to their ability to make an exchange reaction with disulphide groups of mucus or through an oxidation reaction with cysteine residues of mucus glycoproteins both resulting in the formation of disulphide bonds between derivatives and mucus [110][111][112][113]. For this reason, since non-substituted amino groups remained on the chitosan backbone, a multifunctional derivative of chitosan, containing both quaternary ammonium and thiol groups (QA-Ch-SH) was obtained [114].…”

Section: No-[nn-diethylaminomethyl(diethyldimethylene Ammonium)nmetmentioning

confidence: 99%

Quaternary Ammonium Chitosans: The Importance of the Positive Fixed Charge of the Drug Delivery Systems

Fabiano

Beconcini

Migone

et al. 2020

IJMS

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As a natural polysaccharide, chitosan has good biocompatibility, biodegradability and biosecurity. The hydroxyl and amino groups present in its structure make it an extremely versatile and chemically modifiable material. In recent years, various synthetic strategies have been used to modify chitosan, mainly to solve the problem of its insolubility in neutral physiological fluids. Thus, derivatives with negative or positive fixed charge were synthesized and used to prepare innovative drug delivery systems. Positively charged conjugates showed improved properties compared to unmodified chitosan. In this review the main quaternary ammonium derivatives of chitosan will be considered, their preparation and their applications will be described to evaluate the impact of the positive fixed charge on the improvement of the properties of the drug delivery systems based on these polymers. Furthermore, the performances of the proposed systems resulting from in vitro and ex vivo experiments will be taken into consideration, with particular attention to cytotoxicity of systems, and their ability to promote drug absorption.

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Thiolated polymers: Bioinspired polymers utilizing one of the most important bridging structures in nature

Cited by 102 publications

References 387 publications

Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems

Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems

Mucopenetrating Zwitterionic Micelles

Quaternary Ammonium Chitosans: The Importance of the Positive Fixed Charge of the Drug Delivery Systems

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