Comparative mucoadhesive study of hyaluronic acid‐based conjugates on different mucosae

Laffleur, Flavia

doi:10.1002/app.46071

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…Non-PEGylated HA-LX were able to diffuse through mucus, although HA is normally used as a biopolymer for mucoadhesive systems implicated on the entanglement of polymeric chains with mucin fibers. 45,46 In the present work the presence of HA increase LX diffusion in the ±4:1 charge ratio. In vitro and in vivo studies showed that the HA coating on a nanocomplexation formed insulin/L-penetrating nanoparticles enhanced mucopenetrating ability through intestinal mucus layer after oral administration.…”

Section: Resultssupporting

confidence: 51%

Mucopenetrating lipoplexes modified with PEG and hyaluronic acid for CD44-targeted local siRNA delivery to the lungs

et al. 2019

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RNA interfering technology has become a successful strategy for targeted gene silencing through the use of efficient delivery systems. A nanocarrier must be especially designed when considering unusual routes due to RNA instability in biological medium. Lung delivery provides extensive area of absorption and alveolar deposition, non-invasiveness and local action. However, biological barriers such as lung mucus are a great challenge to the efficient delivery of nanocarriers for therapeutic purpose. Here, we studied the diffusion of mucopenetrating lipoplexes (LX) modified with hyaluronic acid (HA) and polyethylene glycol (PEG) for the local delivery of siRNA to the lungs. PEG is commonly used for the design of mucus-penetrating nanoparticles, while the combination with HA polymer provides additional selective targeting to lung tumor cells overexpressing CD44 receptors. Cationic liposomes modified with HA and PEG in the respective concentrations of 10 and 15% (w/v) and 5, 10 and 15% (molar ratio) were prepared by ethanol injection and mixed with siRNA molecules for LX formation. Multiple particle tracking (MPT) was performed ex vivo to evaluate the influence of the hydrophilic polymers in the particles movement in fresh human airway mucus. In vivo LX distribution in the lungs of mice was analyzed by fluorescence microscopy after intratracheal administration. LX modified with both polymers showed increasing diffusion with Brownian-like trajectories in mucus samples along with the presence of siRNA. PEG12%/HA15%-LX at the charge ratio ±4:1 were more widely distributed throughout mice lungs. Non-PEGylated HA15%-LX at the charge ratio ±4:1 diffused comparably to PEGylated LX, as opposed to non-modified LX, which were trapped in the mucus. LX interaction with A549 lung cells showed that the presence of HA improved cell uptake despite PEGylation, demonstrating that appropriate particle coating with mucoinert polymers and tuning surface charge compose an efficient strategy for siRNA delivery to CD44-expressing lung cells.

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Section: Resultssupporting

confidence: 51%

Mucopenetrating lipoplexes modified with PEG and hyaluronic acid for CD44-targeted local siRNA delivery to the lungs

et al. 2019

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“…The same conclusion was obtained with the pig eye, both normal peak force and area under force-time curve were higher with HA 0.30% than with HA 0.15%. Tensile strength assay on nasal, buccal and vaginal mucosa performed by Laffleur [34] using HA-based conjugates also showed similar adhesive bonding force between HA and the different mucosas, ranging between −0.1 and −0.2 N. According to Hägerström and Edsman, who performed a similar assay, the strengthening might arise from the entanglement of the polymer chains and the mucous glycoproteins, the formation of chemical bonds and/or from dehydration of the mucous layer [13]. However, the area under force-time curve values did not meet the same profile as the normal force, there were no significant difference between HA 0.15% vs. Mucin + HA 0.15% and HA 0.30% vs. Mucin + HA 0.30%.…”

Section: Discussionmentioning

confidence: 99%

Useful In Vitro Techniques to Evaluate the Mucoadhesive Properties of Hyaluronic Acid-Based Ocular Delivery Systems

et al. 2018

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Polymer-based eye drops are the most used drug delivery system to treat dry eye disease (DED). Therefore, the mucoadhesion between the polymer and the ocular mucin is crucial to ensure the efficacy of the treatment. In this context, the present study aimed to evaluate the potential use of in vitro methods to study the mucoadhesion of eye drop solutions and, specifically to evaluate the efficacy of two hyaluronic acid-based formulations (HA), HA 0.15% and 0.30% (w/v) to treat DED. Rheology methods and zeta potential determination were used to study the mucoadhesive properties of both eye drop solutions. All results indicated that interactions occurred between the mucin and the HA, being stronger with HA 0.30%, due to the physical entanglements and hydrogen bounding. In vitro tests on ARPE-19 cell line were performed using a 2D and a 3D dry eye model and the results have shown that pre-treated cells with HA showed a morphology more similar to the hydrated cells in both products, with a high survival rate. The in vitro techniques used in this study have been shown to be suitable to evaluate and predict mucoadhesive properties and the efficacy of the eye drops on relief or treatment of DED. The results obtained from these methods may help in inferring possible in vivo effects.

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“…131 Similarly, hyaluronic acid (HA) functionalized with sulfhydryl cysteine groups (HA-SH) significantly outperformed unmodified HA in terms of tensile strength, total work of adhesion, and maximum detachment force in nasal, buccal, and vaginal tissue. 132 To increase the mucoadhesive capacity of chitosan, Kim et al utilized a mussel-inspired adhesion approach and synthesized catechol-functionalized chitosan (Chi-C). 133 As shown in Figure 3, catechols can oxidize to form irreversible covalent bonds with thiols and amines within mucus, leading to greater bioavailability and retention time of Chi-C in the GI tract following oral administration.…”

Section: Mucoadhesion Mucoadhesion Has Been Widelymentioning

confidence: 99%

“…SH-modified alginate possessed a ∼4-fold higher work of adhesion when applied on freshly excised mucosa as compared to unmodified alginate . Similarly, hyaluronic acid (HA) functionalized with sulfhydryl cysteine groups (HA-SH) significantly outperformed unmodified HA in terms of tensile strength, total work of adhesion, and maximum detachment force in nasal, buccal, and vaginal tissue . To increase the mucoadhesive capacity of chitosan, Kim et al utilized a mussel-inspired adhesion approach and synthesized catechol-functionalized chitosan (Chi-C) .…”

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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Comparative mucoadhesive study of hyaluronic acid‐based conjugates on different mucosae

Cited by 8 publications

References 23 publications

Mucopenetrating lipoplexes modified with PEG and hyaluronic acid for CD44-targeted local siRNA delivery to the lungs

Mucopenetrating lipoplexes modified with PEG and hyaluronic acid for CD44-targeted local siRNA delivery to the lungs

Useful In Vitro Techniques to Evaluate the Mucoadhesive Properties of Hyaluronic Acid-Based Ocular Delivery Systems

Hydrogels for Mucosal Drug Delivery

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