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The intracellular fate and transport mechanism of shape, size and rigidity varied nanocarriers for understanding their oral delivery efficiency
Abstract
Nanocarriers have become an effective strategy to overcome epithelial absorption barriers. During the absorption process, the endocytosis mechanisms, cell internalization pathways, and transport efficiency of nanocarriers are greatly impacted by their physical properties. To understand the relationship between physical properties of nanocarriers and their abilities overcoming multiple absorption barriers, nanocarriers with variable physical properties were prepared via self-assembly of hydrolyzed α-lactalbumin peptide fragments. The impacts of size, shape, and rigidity of nanocarriers on epithelial cells endocytosis mechanisms, internalization pathways, transport efficiency, and bioavailability were studied systematically. The results showed that nanospheres were mainly internalized via clathrin-mediated endocytosis, which was then locked in lysosomes and degraded enzymatically in cytoplasm. While macropinocytosis was the primary pathway of nanotubes and transported to the endoplasmic reticulum and Golgi apparatus, resulting in a high drug concentration and sustained release in cytoplasm. Besides, nanotubes can overcome the multi-drug resistance by inhibiting the P-glycoprotein efflux. Furthermore, nanotubes can open intercellular tight-junctions instantaneously and reversibly, which promotes transport into blood circulation. The aqueous solubility of hydrophobic bioactive mangiferin (Mgf) was improved by nanocarriers. Most importantly, the bioavailability of Mgf was the high…
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“Advances such as nanogels, lipid carriers and phospholipid complexes have improved absorption and stability (23,192,193).”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [23]
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Metadata
- Authors
- Li, X., Jafari, S. M., Zhou, F., Hong, H., Jia, X., Mei, X., Hou, G., Yuan, Y., Liu, B., Chen, S., Gong, Y., Yan, H., Chang, R., Zhang, J., Ren, F., & Li, Y.
- Affiliations
- China Agricultural University (CN)
- Gorgan University of Agricultural Sciences and Natural Resources (IR)
- South China University of Technology (CN)
- Corresponding author
- Li, Xin
- Li, Yuan
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2023-03
- Volume
- 294
- Pages
- 121995
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W4313643485
- Cited by
- 100
- References
- 63
- Citations by year
- 2026: 36 · 2025: 28 · 2024: 27 · 2023: 9
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31772014, 31972202, 32172345)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- nanocarriers, oral drug delivery, nanotubes, nanospheres, endocytosis, clathrin-mediated endocytosis, macropinocytosis, lysosomal degradation, bioavailability, mangiferin, P-glycoprotein inhibition, tight junction opening, streptozotocin-induced diabetes, hydrophobic drug solubility
- MeSH terms
- Biological Transport, Drug Carriers, Epithelial Cells, Lactalbumin, Mouth, Intracellular Space, Nanoparticles
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