Insulin loaded mucus permeating nanoparticles: Addressing the surface characteristics as feature to improve mucus permeation

Sousa, Irene Pereira de; Moser, Thomas; Steiner, Corinna; Fichtl, Barbara; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ijpharm.2016.01.022

Cited by 56 publications

(28 citation statements)

References 22 publications

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“…In addition to PEGylation, N-(2-hydroxypropyl) methacrylamide polymer (pHPMA) 174,176,177 and poly(vinyl alcohol) (PVA) 178 were recently tested as alternative mucoinert coatings, with some success. A dense coating of opposite charges has shown effectiveness in multiple different contexts, including viruses (as discussed above), self-assembled nanoparticles comprised of distinct ratios of polycationic chitosan and polyanionic poly(acrylic acid) (also in mucus), 26,179 zwitterionic dilauroylphosphatidylcholine monolayer-coated nanoparticles (in intestinal mucus), 180 and liposomes with zwitterionic dipalmitoyl phosphatidylcholine membranes (in biofilms and respiratory mucus as an inhaled treatment carrying amikacin, an aminoglycoside; currently in clinical trials). 172 Not all of these coatings provide ideal protection against gel interactions, and in particular polymer brushes form a useful physical adsorption barrier in addition to a biochemical one.…”

Section: Selective Transport Of Objects On the Order Of Mesh Sizementioning

confidence: 99%

The particle in the spider's web: transport through biological hydrogels

2017

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Biological hydrogels such as mucus, extracellular matrix, biofilms, and the nuclear pore have diverse functions and compositions, but all act as selectively permeable barriers to the diffusion of particles. Each barrier has a crosslinked polymeric mesh that blocks penetration of large particles such as pathogens, nanotherapeutics, or macromolecules. These polymeric meshes also employ interactive filtering, in which affinity between solutes and the gel matrix controls permeability. Interactive filtering affects the transport of particles of all sizes including peptides, antibiotics, and nanoparticles and in many cases this filtering can be described in terms of the effects of charge and hydrophobicity. The concepts described in this review can guide strategies to exploit or overcome gel barriers, particularly for applications in diagnostics, pharmacology, biomaterials, and drug delivery.

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Section: Selective Transport Of Objects On the Order Of Mesh Sizementioning

confidence: 99%

The particle in the spider's web: transport through biological hydrogels

2017

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“…PEGylation is one of the approaches that used PEG coat as hydrophilic mucus inert polymer to facilitate mucus penetration of insulin‐loaded carriers . Virus‐mimicking strategy has been combined with PEGylation technique in a study for oral insulin delivery as a model of utilizing two different concepts for mucus penetration systems . The specific design, PEG molecular weight requirements, limited cellular uptake and induction of anti‐PEG antibodies might be considered potential limitations of PEGylation technology .…”

Section: Less Invasive Insulin Deliverymentioning

confidence: 99%

“…[85] Chitosan-4-thiobutylamidine insulin-loaded tablets showed controlled release in non-diabetic rats for over 8 h. [86] Mucus penetration is another technology introduced to overcome the dynamic upstream mucus barrier resulted from its rapid turnover kinetics. [87][88][89] Efficient mucus penetration of an insulin carrier requires highly densely charged surface (virus-mimicking strategy), coating of insulin carrier with hydrophilic mucus inert polymer and neutral to slightly negative charged surface (to minimize electrostatic interaction with mucus). [87] PEGylation is one of the approaches that used PEG coat as hydrophilic mucus inert polymer to facilitate mucus penetration of insulin-loaded carriers.…”

Section: Formulation Barriermentioning

confidence: 99%

Oral insulin delivery: existing barriers and current counter-strategies

Gedawy

Martinez

Al‐Salami

et al. 2017

Journal of Pharmacy and Pharmacology

128

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Objectives The chronic and progressive nature of diabetes is usually associated with micro-and macrovascular complications where failure of pancreatic b-cell function and a general condition of hyperglycaemia is created. One possible factor is failure of the patient to comply with and adhere to the prescribed insulin due to the inconvenient administration route. This review summarizes the rationale for oral insulin administration, existing barriers and some counter-strategies trialled. Key findings Oral insulin mimics the physiology of endogenous insulin secreted by pancreas. Following the intestinal absorption of oral insulin, it reaches the liver at high concentration via the portal vein. Oral insulin on the other hand has the potential to protect pancreatic b-cells from autoimmune destruction. Structural modification, targeting a particular tissue/receptor, and the use of innovative pharmaceutical formulations such as nanoparticles represent strategies introduced to improve oral insulin bioavailability. They showed promising results in overcoming the hurdles facing oral insulin delivery, although delivery is far from ideal. Summary The use of advanced pharmaceutical technologies and further research in particulate carrier system delivery predominantly nanoparticle utilization would offer useful tools in delivering insulin via the oral route which in turn would potentially improve diabetic patient compliance to insulin and the overall management of diabetes.

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“…BET analysis also demonstrated the presence of mesopores of about 20 nm for the polymer, leading to similar characteristics to those of a type IV isotherm, so their nanospace pores can be distinguished from NIPs. In the case of NIPs, the pore diameter was larger and the isotherm exhibited a type III curve characteristic due to the nonporous structure with low interaction (28). That insulin recognition sites formed within the nanospace pores was further corroborated by a bomb calorimeter.…”

Section: Surface Area and Pore Size Distribution Of Insulin Mipsmentioning

confidence: 74%

Biomimetic insulin-imprinted polymer nanoparticles as a potential oral drug delivery system

2017

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In this study, we investigate molecularly imprinted polymers (MIPs), which form a three-dimensional image of the region at and around the active binding sites of pharmaceutically active insulin or are analogous to b cells bound to insulin. This approach was employed to create a welldefined structure within the nanospace cavities that make up functional monomers by cross-linking. The obtained MIPs exhibited a high adsorption capacity for the target insulin, which showed a significantly higher release of insulin in solution at pH 7.4 than at pH 1.2. In vivo studies on diabetic Wistar rats showed that the fast onset within 2 h is similar to subcutaneous injection with a maximum at 4 h, giving an engaged function responsible for the duration of glucose reduction for up to 24 h. These MIPs, prepared as nanosized material, may open a new horizon for oral insulin delivery.

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Insulin loaded mucus permeating nanoparticles: Addressing the surface characteristics as feature to improve mucus permeation

Cited by 56 publications

References 22 publications

The particle in the spider's web: transport through biological hydrogels

The particle in the spider's web: transport through biological hydrogels

Oral insulin delivery: existing barriers and current counter-strategies

Biomimetic insulin-imprinted polymer nanoparticles as a potential oral drug delivery system

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