Aldehyde-functional thermoresponsive diblock copolymer worm gels exhibit strong mucoadhesion

Brotherton, Emma E.; Neal, Thomas J.; Kaldybekov, Daulet B.; Smallridge, Mark J.; Khutoryanskiy, Vitaliy V.; Armes, Steven P.

doi:10.1039/d2sc02074b

Cited by 15 publications

(16 citation statements)

References 83 publications

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“…Recently, we reported that PAGEO5MA-functionalized diblock copolymer worm gels exhibit strong mucoadhesive behavior. 68 This is because the pendent aldehyde groups can react with the primary amine groups that are located at the surface of porcine urinary bladder mucosa. 68 Conversely, the corresponding PGEO5MA-functionalized diblock copolymer worm gels exhibit minimal mucoadhesion.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…68 This is because the pendent aldehyde groups can react with the primary amine groups that are located at the surface of porcine urinary bladder mucosa. 68 Conversely, the corresponding PGEO5MA-functionalized diblock copolymer worm gels exhibit minimal mucoadhesion. In view of these observations, quartz crystal microbalance (QCM) experiments were performed to determine the extent to which a model globular protein (bovine serum albumin, BSA) interacts with (i) a PGEO5MA brush and (ii) the corresponding PAGEO5MA brush.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Hydrophilic Aldehyde-Functional Polymer Brushes: Synthesis, Characterization, and Potential Bioapplications

Brotherton

Johnson

Smallridge³

et al. 2023

Macromolecules

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Surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) is used to polymerize a cis-diol-functional methacrylic monomer (herein denoted GEO5MA) from planar silicon wafers. Ellipsometry studies indicated dry brush thicknesses ranging from 40 to 120 nm. The hydrophilic PGEO5MA brush is then selectively oxidized using sodium periodate to produce an aldehyde-functional hydrophilic PAGEO5MA brush. This post-polymerization modification strategy provides access to significantly thicker brushes compared to those obtained by surface-initiated ARGET ATRP of the corresponding aldehyde-functional methacrylic monomer (AGEO5MA). The much slower brush growth achieved in the latter case is attributed to the relatively low aqueous solubility of the AGEO5MA monomer. X-ray photoelectron spectroscopy (XPS) analysis confirmed that precursor PGEO5MA brushes were essentially fully oxidized to the corresponding PAGEO5MA brushes within 30 min of exposure to a dilute aqueous solution of sodium periodate at 22 °C. PAGEO5MA brushes were then functionalized via Schiff base chemistry using an amino acid (histidine), followed by reductive amination with sodium cyanoborohydride. Subsequent XPS analysis indicated that the mean degree of histidine functionalization achieved under optimized conditions was approximately 81%. Moreover, an XPS depth profiling experiment confirmed that the histidine groups were uniformly distributed throughout the brush layer. Surface ζ potential measurements indicated a significant change in the electrophoretic behavior of the zwitterionic histidinefunctionalized brush relative to that of the non-ionic PGEO5MA precursor brush. The former brush exhibited cationic character at low pH and anionic character at high pH, with an isoelectric point being observed at around pH 7. Finally, quartz crystal microbalance studies indicated minimal adsorption of a model globular protein (BSA) on a PGEO5MA brush-coated substrate, whereas strong protein adsorption via Schiff base chemistry occurred on a PAGEO5MA brush-coated substrate.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Hydrophilic Aldehyde-Functional Polymer Brushes: Synthesis, Characterization, and Potential Bioapplications

Brotherton

Johnson

Smallridge³

et al. 2023

Macromolecules

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“…More recent studies have synthesized aldehyde copolymers with mucoadhesion force to mucosa comparable to that of chitosan and other functional groups. 143,144 3.2. Viscoelasticity.…”

Section: T H Imentioning

confidence: 99%

“…Maleimide-functionalized PEGylated polymers such as alginate-polyethylene glycol-maleimide (Alg-PEGM) and poly(lactide- co -glycolide)- block -polyethylene glycol-maleimide (PLGA-PEG-Mal) showed a propensity to aggregate with mucins and showed increased retention to the urinary bladder mucosa, respectively. , Acrylate-chitosan and polyethylene glycol diacrylate polymers have also been explored. , Similarly, methacrylate-functionalized materials have been demonstrated to exhibit enhanced adhesion to mucosal tissues. , Furthermore, designing copolymer hydrogels containing acrylate and methacrylate groups may strengthen mucoadhesion. , In addition, aldehyde-functionalized polymers have been known to enhance mucoadhesion. More recent studies have synthesized aldehyde copolymers with mucoadhesion force to mucosa comparable to that of chitosan and other functional groups. , …”

Section: Formulation Strategiesmentioning

confidence: 99%

Hydrogels for Mucosal Drug Delivery

Yeruva

Yang

Doski

et al. 2023

ACS Appl. Bio Mater.

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Mucosal tissues are often a desirable site of drug action to treat disease and engage the immune system. However, systemically administered drugs suffer from limited bioavailability in mucosal tissues where technologies to enable direct, local delivery to these sites would prove useful. In this Spotlight on Applications article, we discuss hydrogels as an attractive means for local delivery of therapeutics to address a range of conditions affecting the eye, nose, oral cavity, gastrointestinal, urinary bladder, and vaginal tracts. Considering the barriers to effective mucosal delivery, we provide an overview of the key parameters in the use of hydrogels for these applications. Finally, we highlight recent work demonstrating their use for inflammatory and infectious diseases affecting these tissues.

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“…20,21 Hydrogel-based drug delivery systems were elaborated with the aim of intravesical administration. 22,23 Particular attention is paid to emulsion systems intended for intravesical drug delivery due to their ability to immobilize both hydrophobic and hydrophilic molecules. 24−27 Mucoadhesive emulsions are of increasing interest given the combination of properties which are beneficial for intravesical drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Mucoadhesive Emulsion Microgels for Intravesical Drug Delivery: Preparation, Retention at Urothelium, and Biodistribution Study

Saveleva,

Lobanov,

Gusliakova

et al. 2023

ACS Appl. Mater. Interfaces

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The intravesical instillation procedure is a proven method in modern urology for the treatment of bladder diseases. However, the low therapeutic efficiency and painfulness of the instillation procedure are significant limitations of this method. In the present study, we propose an approach to solving this problem by using microsized mucoadhesive macromolecular carriers based on whey protein isolate with the possibility of prolonged release of drugs as a drug delivery system. The optimal water-to-oil ratio (1:3) and whey protein isolate concentration (5%) were determined to obtain emulsion microgels with sufficient loading efficiency and mucoadhesive properties. The droplet diameter of emulsion microgels varies from 2.2 to 3.8 μm. The drug release kinetics from the emulsion microgels was evaluated. The release of the model dye in saline and artificial urine in vitro was observed for 96 h and reached up to 70% of loaded cargo for samples. The effect of emulsion microgels on the morphology and viability of two cell lines was observed: L929 mouse fibroblasts (normal adherent cells) and THP-1 human monocytes (cancer suspension cells). Developed emulsion microgels (5%, 1:3 and 1:5) showed sufficient mucoadhesion to a porcine bladder urothelium ex vivo. The biodistribution of emulsion microgels (5%, 1:3 and 1:5) in mice (n = 3) after intravesical (instillation) and systemic (intravenous) administration was assessed in vivo and ex vivo using nearinfrared fluorescence live imaging for real time. It was demonstrated that intravesical instillation allows approximately 10 times more efficient accumulation of emulsion microgels in the mice urinary bladder in vivo 1 h after injection compared to systemic injection. The retention of the emulsion of mucoadhesive microgels in bladders after the intravesical instillation was observed for 24 h.

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Aldehyde-functional thermoresponsive diblock copolymer worm gels exhibit strong mucoadhesion

Abstract: Optimizing the aldehyde content of thermoresponsive diblock copolymer worm gels via periodate oxidation leads to mucoadhesion performance comparable to that of chitosan (a gold standard positive control) in a fluorescence assay using porcine mucosa.

Cited by 15 publications

References 83 publications

Hydrophilic Aldehyde-Functional Polymer Brushes: Synthesis, Characterization, and Potential Bioapplications

Hydrophilic Aldehyde-Functional Polymer Brushes: Synthesis, Characterization, and Potential Bioapplications

Hydrogels for Mucosal Drug Delivery

Mucoadhesive Emulsion Microgels for Intravesical Drug Delivery: Preparation, Retention at Urothelium, and Biodistribution Study

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