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Recent Progress of Chitosan and Chitosan Derivatives-Based Nanoparticles: Pharmaceutical Perspectives of Oral Insulin Delivery

Seyam, Salma, Nordin, Norsyafikah Asyilla, Alfatama, Mulham·2020·Pharmaceuticals
DOI 10.3390/ph13100307PMC PMC7602211
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Abstract

Diabetes mellitus is a chronic endocrine disease, affecting more than 400 million people around the world. Patients with poorly controlled blood glucose levels are liable to suffer from life-threatening complications, such as cardiovascular, neuropathy, retinopathy and even premature death. Today, subcutaneous parenteral is still the most common route for insulin therapy. Oral insulin administration is favourable and convenient to the patients. In contrast to injection route, oral insulin delivery mimics the physiological pathway of endogenous insulin secretion. However, oral insulin has poor bioavailability (less than 2%) due to the harsh physiological environment through the gastrointestinal tract (GIT). Over the last few decades, many attempts have been made to achieve an effective oral insulin formulation with high bioavailability using insulin encapsulation into nanoparticles as advanced technology. Various natural polymers have been employed to fabricate nanoparticles as a delivery vehicle for insulin oral administration. Chitosan, a natural polymer, is extensively studied due to the attractive properties, such as biodegradability, biocompatibility, bioactivity, nontoxicity and polycationic nature. Numerous studies were conducted to evaluate chitosan and chitosan derivatives-based nanoparticles capabilities for oral insulin delivery. This review highlights strategies that have been applied in the recent five years to fabricate chitosan/chitosan derivatives-based nanoparticles for oral insulin delivery. A summary of the barriers hurdle insulin absorption rendering its low bioavailability such as physical, chemical and enzymatic barriers are highlighted with an emphasis on the most common methods of chitosan nanoparticles preparation. Nanocarriers are able to improve the absorption of insulin through GIT, deliver insulin to the blood circulation and lower blood glucose levels. In spite of some drawbacks encountered in this technology, chitosan and chitosan derivatives-based nanoparticles are greatly promising entities for oral insulin delivery.

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Figures

Figure 1 Common nanocarriers used for oral protein/peptide delivery.
Figure 1 Common nanocarriers used for oral protein/peptide delivery.CC BY · PubMed Central
Figure 2 Structure of human insulin.
Figure 2 Structure of human insulin.CC BY · PubMed Central
Figure 3 Endogenous insulin pathway under normal physiology (1), orally administered insulin pathway (2) and injected insulin pathway in diabetic patients (3). Created with BioRender.com.
Figure 3 Endogenous insulin pathway under normal physiology (1), orally administered insulin pathway (2) and injected insulin pathway in diabetic patients (3). Created with BioRender.com.CC BY · PubMed Central
Figure 4 Chitosan chemical structure (DD ≥ 50%).
Figure 4 Chitosan chemical structure (DD ≥ 50%).CC BY · PubMed Central
Figure 5 Schematic diagram of chitosan nanoparticles prepared via ionic gelation/polyelectrolyte complexation.
Figure 5 Schematic diagram of chitosan nanoparticles prepared via ionic gelation/polyelectrolyte complexation.CC BY · PubMed Central
Figure 6 Schematic diagram of chitosan nanoparticles prepared via reverse micellar method.
Figure 6 Schematic diagram of chitosan nanoparticles prepared via reverse micellar method.CC BY · PubMed Central
Figure 7 Schematic diagram of chitosan nanoparticles prepared via emulsion solvent diffusion.
Figure 7 Schematic diagram of chitosan nanoparticles prepared via emulsion solvent diffusion.CC BY · PubMed Central
Figure 8 Schematic diagram of chitosan nanoparticles prepared via electrospray technique.
Figure 8 Schematic diagram of chitosan nanoparticles prepared via electrospray technique.CC BY · PubMed Central
Figure 9 Schematic representation of the interaction between alginate as a polyanion and chitosan as polycation: mixing of the oppositely charged polyelectrolytes leads to formation of a polyelectrolyte complex caused by the electrostatic interactions between the ions.
Figure 9 Schematic representation of the interaction between alginate as a polyanion and chitosan as polycation: mixing of the oppositely charged polyelectrolytes leads to formation of a polyelectrolyte complex caused by the electrostatic interactions between the ions.CC BY · PubMed Central
Figure 10 Schematic representation of the double emulsion method used to prepare insulin-loaded polyelectrolyte complexes. Positively charged chitosan nanoparticles (CSNPs) and negatively charged alginate nanoparticles (AlgNPs) are prepared, respectively, then two kinds of nanoparticles are mixed together to self-assemble forming polyelectrolyte complexes by electrostatic interaction.
Figure 10 Schematic representation of the double emulsion method used to prepare insulin-loaded polyelectrolyte complexes. Positively charged chitosan nanoparticles (CSNPs) and negatively charged alginate nanoparticles (AlgNPs) are prepared, respectively, then two kinds of nanoparticles are mixed together to self-assemble forming polyelectrolyte complexes by electrostatic interaction.CC BY · PubMed Central

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Metadata

Authors
Seyam, S., Nordin, N. A., & Alfatama, M.
Venue
Pharmaceuticals
Publisher
MDPI AG
Published
2020-10-14
Volume
13
Issue
10
Pages
307
ISSN
1424-8247
DOI
10.3390/ph13100307
PMC
PMC7602211
Cited by
85
References
1
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
University Sultan Zainal Abidin (UniSZA/2018/DPU/07)

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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