Thiolated pectins: In vitro and ex vivo evaluation of three generations of thiomers

Knoll, Patrick; Le, Nguyet‐Minh Nguyen; Wibel, Richard; Baus, Randi Angela; Kali, Gergely; Asim, Mulazim Hussain; Bernkop‐Schnürch, Andreas

doi:10.1016/j.actbio.2021.08.016

Cited by 36 publications

(18 citation statements)

References 37 publications

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“…In accordance with SPT, plain, CS-and CS-Cys-MNA-coated SLN could diffuse into rear segments of the mucus layer while nearly no CS-Cys-and CS-Cys-Cys-coated SLN could reach into segment 5 and posterior of it (Figure 8). To further investigate the beneficial diffusion behavior of CS-Cys-MNAcoated SLN, CS-Cys-MNA was labeled with FITC as conducted by Knoll et al 33 and the experiment was carried out in the same way. Thus, diffusion of CS-Cys-MNA and SLN could be distinguished from each other.…”

Section: Rheological Measurementsmentioning

confidence: 99%

In Vitro Investigation of Thiolated Chitosan Derivatives as Mucoadhesive Coating Materials for Solid Lipid Nanoparticles

et al. 2021

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In the present study, chitosan (CS) was thiolated by introducing l -cysteine via amide bond formation. Free thiol groups were protected with highly reactive 6-mercaptonicotinic acid (6-MNA) and less-reactive l -cysteine, respectively, via thiol/disulfide-exchange reactions. Unmodified CS, l -cysteine-modified thiolated CS (CS-Cys), 6-MNA-S-protected thiolated CS (CS-Cys-MNA), and l -cysteine-S-protected thiolated CS (CS-Cys-Cys) were applied as coating materials to solid lipid nanoparticles (SLN). The strength of mucus interaction followed the rank order plain < CS < CS-Cys-Cys < CS-Cys < CS-Cys-MNA, whereas mucus diffusion followed the rank order CS-Cys < CS-Cys-Cys < CS < CS-Cys-MNA < plain. In accordance with lower reactivity, CS-Cys-Cys-coated SLN were immobilized to a lower extent than CS-Cys-coated SLN, while CS-Cys-MNA-coated SLN dissociated from their coating material resulting in a similar diffusion behavior as plain SLN. Consequently, CS-Cys-Cys-coated SLN and CS-Cys-MNA-coated SLN showed the highest retention on porcine intestinal mucosa by enabling a synergism of efficient mucus diffusion and strong mucoadhesion.

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Section: Rheological Measurementsmentioning

confidence: 99%

In Vitro Investigation of Thiolated Chitosan Derivatives as Mucoadhesive Coating Materials for Solid Lipid Nanoparticles

et al. 2021

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“…This result can be explained as a retraction of these protons from the binding site to enable a less selective HPC–mucin binding mode at higher HPC molecular weights, ultimately consolidating to yield statistically significant complexation. The case where strong associative interactions limit the overall interaction of a given polymer have been observed elsewhere, where strongly reactive groups impede the overall performance of adhesive systems compared to less reactive analogs . Finally, despite following a similar directional trend to CMC, HPC’s difference profile remains unique, reinforcing the concept that similar polymer molecular structures do not inherently enable similar mucoadhesive interaction mechanisms as the underlying materials are adjusted.…”

Section: Resultsmentioning

confidence: 64%

“…The case where strong associative interactions limit the overall interaction of a given polymer have been observed elsewhere, where strongly reactive groups impede the overall performance of adhesive systems compared to less reactive analogs. 24 Finally, despite following a similar directional trend to CMC, HPC's difference profile remains unique, reinforcing the concept that similar polymer molecular structures do not inherently enable similar mucoadhesive interaction mechanisms as the underlying materials are adjusted. The difference profile arising from increasing the molecular weight of HPMC (86−120 kDa) yields no statistically significant differences between species (Figure 1E) in contrast to the results obtained with the other cellulose derivatives.…”

Section: ■ Results and Discussionmentioning

confidence: 77%

Mechanistic Influence of Polymer Species, Molecular Weight, and Functionalization on Mucin–Polymer Binding Interactions

Watchorn

Stuart

Burns

et al. 2022

ACS Appl. Polym. Mater.

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Improving both systemic and localized delivery of pharmaceuticals by optimizing the delivery vehicle properties is a major area of ongoing research. One such engineered property is mucoadhesion, wherein polymers are tailored to optimize polymer−mucin interactions to increase drug residence times and uptake efficiency. There are many examples of mucoadhesion as a drug delivery modality in the literature, yet the underlying mechanisms remain poorly understood, and its clinical translation is limited. Within this mechanistic lens, we found that nuclear magnetic resonance (NMR) is a powerful tool for uncovering polymer−mucin interactions. We investigated the influence of several polymer design parameters including molecular weight and repeating unit functionalization on mucoadhesion and uncovered several key findings in terms of the influence of these design parameters on polymer−protein intermacromolecular interactions. First, we probed individual polymer species including hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), and carboxymethyl cellulose (CMC) and identified that molecular-weight-driven changes in the polymer−mucin interaction fingerprint result from perturbations in the polymer-specific binding complex. Specifically, we found that CMC and HPC complexes spatially reorient with increasing molecular weight, whereas HPMC complexes do not. We expanded this comparison to include functional group changes to the polymer repeating unit, where we showed that the addition of methyl groups to cellulose derivatives induces a unique binding fingerprint. Next, we expanded the mucoadhesive polymer series to include CMC, HPC, HPMC, poly(acrylic acid) (PAA), and poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) and observed a negative correlation between molecular weight and mucoadhesive interaction intimacy, highlighting the differences across polymer species. Finally, we explored polymers that lack mucin interactions to illustrate the limitations of polymer composition and molecular weight as predictors of mucoadhesive fate. Altogether, these experiments were used to report on mucoadhesive interactions at the atomic level and revealed that polymer design is dependent on both the availability and accessibility of mucoadhesive functional groups.

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“…Therefore, the use of thiolated polymers (modified polymers that contain a thiol group) capable of forming covalent bonds with mucus components enhances the specificity of the interaction and improves the bioadhesive properties [ 27 , 108 ]. Thiolated polymers (such as PAA, CMC, starch, hyaluronic acid, pectin, and chitosan) can show significantly prolonged (up to 25-fold) mucoadhesion compared to the corresponding unmodified polymers, and a clear correlation exists between the number of thiol groups and mucoadhesion [ 47 , 109 , 110 , 111 , 112 ]. Duggan et al [ 113 ] have synthesized thiolated derivatives of PAA (MW 450,000) and polyallylamine (MW 15,000) with the resulting thiol contents in the modified polymers of 400–487 μmol/g.…”

Section: Bioadhesive Polymersmentioning

confidence: 99%

Patches as Polymeric Systems for Improved Delivery of Topical Corticosteroids: Advances and Future Perspectives

Dubashynskaya

Skorik

2022

IJMS

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Mucoadhesive polymer patches are a promising alternative for prolonged and controlled delivery of topical corticosteroids (CS) to improve their biopharmaceutical properties (mainly increasing local bioavailability and reducing systemic toxicity). The main biopharmaceutical advantages of patches compared to traditional oral dosage forms are their excellent bioadhesive properties and their increased drug residence time, modified and unidirectional drug release, improved local bioavailability and safety profile, additional pain receptor protection, and patient friendliness. This review describes the main approaches that can be used for the pharmaceutical R&D of oromucosal patches with improved physicochemical, mechanical, and pharmacological properties. The review mainly focuses on ways to increase the bioadhesion of oromucosal patches and to modify drug release, as well as ways to improve local bioavailability and safety by developing unidirectional -release poly-layer patches. Various techniques for obtaining patches and their influence on the structure and properties of the resulting dosage forms are also presented.

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Thiolated pectins: In vitro and ex vivo evaluation of three generations of thiomers

Cited by 36 publications

References 37 publications

In Vitro Investigation of Thiolated Chitosan Derivatives as Mucoadhesive Coating Materials for Solid Lipid Nanoparticles

In Vitro Investigation of Thiolated Chitosan Derivatives as Mucoadhesive Coating Materials for Solid Lipid Nanoparticles

Mechanistic Influence of Polymer Species, Molecular Weight, and Functionalization on Mucin–Polymer Binding Interactions

Patches as Polymeric Systems for Improved Delivery of Topical Corticosteroids: Advances and Future Perspectives

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