On the synthesis of mucus permeating nanocarriers

Bourganis, Vassilis; Karamanidou, Theodora; Samaridou, Eleni; Karidi, Konstantina; Kammona, Olga; Kiparissides, Costas

doi:10.1016/j.ejpb.2015.01.021

Cited by 45 publications

(24 citation statements)

References 42 publications

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“…With less space between them, PEG chains are organized in a more distended way, minimizing adhesive interactions between nanoparticles core moieties and mucus. 42–44…”

Section: Resultsmentioning

confidence: 99%

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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“…With less space between them, PEG chains are organized in a more distended way, minimizing adhesive interactions between nanoparticles core moieties and mucus. 42–44…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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“…These particles with neutral surface, high surface charge density of polyelectrolyte complexes (PECs), can create a hydrophilic surface that decreases its hydrophobic interactions with mucus and facilitate mucus transport. 42 , 83 CS, an attractive polymer, has been extensively used in oral delivery. The combination of CS and chondroitin sulfate was used to prepare PECs that could penetrate mucus to the higher extent compared with reference nanoparticles.…”

Section: The Effects Of Surface Properties For Oral Bioavailabilitymentioning

confidence: 99%

<p>The Influence of Nanoparticle Properties on Oral Bioavailability of Drugs</p>

Wang

Feng

et al. 2020

IJN

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Oral administration has been the most common therapeutic regimen in various diseases because of its high safety, convenience, lower costs, and high compliance of patients. However, susceptible in hostile gastrointestinal (GI) environment, many drugs show poor permeability across GI tract mucus and intestinal epithelium with poor oral absorption and limited therapeutic efficacy. In recent years, nanoparticulate drug delivery systems (NDDS) have become a hot research spot because of their unique advantages including protecting drug from premature degrading and interacting with the physiological environment, increasing intracellular penetration, and enhancing drug absorption. However, a slight change in physicochemistry of nanoparticles can significantly impact their interaction with biological pathways and alter the oral bioavailability of drugs. Hence, this review focuses on the factors affecting oral bioavailability from two aspects. On the one hand, the factors are the biochemical and physiological barriers in oral drugs delivery. On the other hand, the factors are the nanoparticle properties including size, surface properties, and shape of nanoparticles.

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“…The permeability of compounds can be evaluated by their ability to pass through the mucus and epithelial cells from the intestinal cavity into the wall. However, a membrane filter simply covered by the mucus layer can generate a comparison of the penetration of compounds without the existence of an epithelial barrier and can be used to evaluate the diffusion of different substances through the mucus layer [26–29]. A study used the Caco‐2/HT29‐MTX coculture cell model to evaluate the transcellular permeation of nanoparticles by virtue of not only the presence of the mucus layer but also a TEER value that was close to that of the intestinal epithelium [30].…”

Section: Simulating the Gastrointestinal Mucus Barriermentioning

confidence: 99%

Oral drug delivery with nanoparticles into the gastrointestinal mucosa

Liu¹,

Leng²,

Liu³

2020

Fundamemntal Clinical Pharma

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The oral route of protein and peptide drugs has been a popular method of drug delivery in recent years, although it is often a challenge to achieve effective drug release and minimize the barrier functions of the gastrointestinal tract. Gastrointestinal mucosa can capture and remove harmful substances; similarly, it can limit the absorption of drugs. Many drugs are effectively captured by the mucus and rapidly removed, making it difficult to control the release of drugs in the gastrointestinal tract. The use of drug carrier systems can overcome the mucosal barrier and significantly improve bioavailability. Nanoparticle drug carriers can protect the drug from degradation, transporting it to a predetermined location in the gastrointestinal tract to achieve more efficient and sustained drug delivery. It is becoming clearer that the characteristics of nanoparticles, such as particle size, charge, and hydrophobicity, are related to permeability of the mucosal barrier. This review focuses on the latest research progress of nanoparticles to penetrate the mucosal barrier, including the delivery methods of nanoparticles on the surface of gastrointestinal mucosa, and aims to summarize how successful oral nanoparticle delivery systems can overcome this biological barrier in the human body. In addition, the in vitro model based on gastrointestinal mucus is an important tool for drug research and development. Here, we discuss different types of drug delivery systems and their advantages and disadvantages in design and potential applications. Similarly, we reviewed and summarized various methods for evaluating oral nanoparticles in in vitro and in vivo models.

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On the synthesis of mucus permeating nanocarriers

Cited by 45 publications

References 42 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

<p>The Influence of Nanoparticle Properties on Oral Bioavailability of Drugs</p>

Oral drug delivery with nanoparticles into the gastrointestinal mucosa

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