Mucoadhesion: mucin-polymer molecular interactions

Pham, Quoc Dat; Nojd, Söfi; Edman, Martin; Lindell, Katarina; Topgaard, Daniel; Wahlgren, Marie

doi:10.1016/j.ijpharm.2021.121245

Cited by 34 publications

(16 citation statements)

References 42 publications

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“…In these experiments, we are observing the solvated behavior of PVP, where the polymer is free to reorient to its most energetically favorable conformation in solution. Under these conditions, our results showing a lack of binding between PVP and mucin in free solution are supported by other recent mechanistic investigations . The literature-reported behavior of Poloxamer 407 also possesses contradictory results when considering its mucoadhesive properties.…”

Section: Resultssupporting

confidence: 86%

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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Section: Resultssupporting

confidence: 86%

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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show abstract

“…The strongest mucoadhesive properties were observed under acidic pH which is clearly due to hydrogen bonding of acidic carboxylic groups with mucin. 40 Catechol modification of alginate nanoparticles with catechol functional groups bearing dopamine hydrochloride was reported by Sahatsapan et al This modification led to an excellent increase in mucoadhesive properties due to the irreversible interaction of catechol groups with amino and thiol moieties in mucin glycoproteins of porcine bladder mucosa. The entrapped Garcinia mangostana L. extract achieved a constant release for up to 8 h and followed zero order kinetics.…”

Section: Chemical Modifications Of Polymersmentioning

confidence: 98%

Recent advances in functionally modified polymers for mucoadhesive drug delivery

2022

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“…Similarly, NMR uses magnetic excitation to monitor interactions between different species in solution and generally encounters the same challenges as FTIR . Nevertheless NMR-based methods continue to evolve, and some progress has been made in understanding polymer–mucin interactions using relaxometry, evolution of line width, and macromolecular saturation transfer …”

Section: Strategies To Study Mucus-nanoparticle Interactionsmentioning

confidence: 99%

“…Similarly, NMR uses magnetic excitation to monitor interactions between different species in solution and generally encounters the same challenges as FTIR. 52 Nevertheless NMR-based methods continue to evolve, and some progress has been made in understanding polymer−mucin interactions using relaxometry, 292 evolution of line width, 293 and macromolecular saturation transfer. 294 While previously mentioned techniques are used preferentially for mucoadhesive systems, multiple particle tracking (MPT) can be implemented for both mucoadhesive and mucopenetrating formulations.…”

Section: Strategies To Study Mucus-nanoparticlementioning

confidence: 99%

Untangling Mucosal Drug Delivery: Engineering, Designing, and Testing Nanoparticles to Overcome the Mucus Barrier

Watchorn

Clasky

Prakash

et al. 2022

ACS Biomater. Sci. Eng.

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Mucus is a complex viscoelastic gel and acts as a barrier covering much of the soft tissue in the human body. High vascularization and accessibility have motivated drug delivery to various mucosal surfaces; however, these benefits are hindered by the mucus layer. To overcome the mucus barrier, many nanomedicines have been developed, with the goal of improving the efficacy and bioavailability of drug payloads. Two major nanoparticle-based strategies have emerged to facilitate mucosal drug delivery, namely, mucoadhesion and mucopenetration. Generally, mucoadhesive nanoparticles promote interactions with mucus for immobilization and sustained drug release, whereas mucopenetrating nanoparticles diffuse through the mucus and enhance drug uptake. The choice of strategy depends on many factors pertaining to the structural and compositional characteristics of the target mucus and mucosa. While there have been promising results in preclinical studies, mucus−nanoparticle interactions remain poorly understood, thus limiting effective clinical translation. This article reviews nanomedicines designed with mucoadhesive or mucopenetrating properties for mucosal delivery, explores the influence of site-dependent physiological variation among mucosal surfaces on efficacy, transport, and bioavailability, and discusses the techniques and models used to investigate mucus−nanoparticle interactions. The effects of non-homeostatic perturbations on protein corona formation, mucus composition, and nanoparticle performance are discussed in the context of mucosal delivery. The complexity of the mucosal barrier necessitates consideration of the interplay between nanoparticle design, tissue-specific differences in mucus structure and composition, and homeostatic or disease-related changes to the mucus barrier to develop effective nanomedicines for mucosal delivery.

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Mucoadhesion: mucin-polymer molecular interactions

Cited by 34 publications

References 42 publications

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

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

Recent advances in functionally modified polymers for mucoadhesive drug delivery

Untangling Mucosal Drug Delivery: Engineering, Designing, and Testing Nanoparticles to Overcome the Mucus Barrier

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