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Published on: February 8, 2017
Tracking translocation of glucan microparticles targeting M cells: implications for oral drug delivery
Yunchang Xie1, Xiongwei Hu, Haisheng He
1School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China. wuwei@shmu.edu.cn fd_luyi@fudan.edu.cn.
Abstract:
Taking advantage of its ability to deal with exogenous pathogens, the M cell passage has proven to be the most reliable pathway for entry of particulates, thus creating opportunities for oral immunization and delivery of biomacromolecules. Albeit a well-known story, the underlying mechanisms of this pathway are not yet well understood, especially concerning direct evidence of translocation of particulates. Herein, model glucan microparticles (GMs) targeting M cells are employed to track translocation through M cell pathways as well as to various organs via the systemic circulation. GMs were first labeled with a novel kind of near-infrared fluorescent water-quenching probe through encapsulation and locking by stearin. In vivo live imaging indicates prolonged residence of GMs in the gastrointestinal tract for as long as 12 h. GMs are found to be gradually absorbed from the ligated ileum segment but little from the jejunum. Histological examination using confocal laser scanning microscopy (CLSM) confirms distribution of GMs to the basolateral side of the ileum through Peyer's patches. However, no detectable fluorescence can be observed in any other organs or tissues until 12 h after administration. After 12 h, GMs can be found in the liver, spleen and lung. At 24 h, GMs accumulate in these organs with approximately 2.3% of the total amount. Repeated administration for three consecutive days augments total accumulation to as high as 4.5%. By tracking GM-bound fluorescence, the particles can be accurately located in these organs. GMs can be transported across Caco-2/Raji and Caco-2/Raji/J774A.1 co-culture monolayers, but not Caco-2 monolayers, in a time-dependent manner. As observed by CLSM, GMs can be voraciously engulfed with as many as 10-15 particles per cell. Evidence of translocation of GMs indicates that GMs can be absorbed through the M cell pathway located at Peyer's patches, especially in the ileum, and translocated to reticulo-endothelial organs.
Insights
Glucan microparticles (GMs) utilize the M cell pathway in the ileum for oral delivery. These particles translocate to organs like the liver and spleen, demonstrating potential for targeted delivery and immunization.
Area of Science:
- Biomaterials Science
- Immunology
- Gastroenterology
Background:
- M cell pathway is crucial for oral delivery of biomacromolecules and immunization.
- Mechanisms of M cell translocation of particulates remain poorly understood.
- Direct evidence of particulate translocation is needed.
Purpose of the Study:
- To track the translocation of model glucan microparticles (GMs) through M cell pathways.
- To investigate the systemic distribution of GMs after oral administration.
- To provide direct evidence of particulate translocation via M cells.
Main Methods:
- Model glucan microparticles (GMs) labeled with near-infrared fluorescent probes.
- In vivo live imaging of GMs in the gastrointestinal tract.
- Histological examination using confocal laser scanning microscopy (CLSM).
- Co-culture models (Caco-2/Raji and Caco-2/Raji/J774A.1) to assess particle transport.
Main Results:
- GMs showed prolonged residence in the gastrointestinal tract (up to 12 h).
- Absorption of GMs was significant from the ileum but minimal from the jejunum.
- CLSM confirmed GM distribution to the basolateral side of the ileum via Peyer's patches.
- GMs were detected in the liver, spleen, and lungs 12-24 h post-administration, with accumulation increasing after repeated dosing.
- GMs were transported across specific co-culture models, indicating cellular uptake and translocation.
Conclusions:
- Glucan microparticles are absorbed via the M cell pathway in Peyer's patches, primarily in the ileum.
- Translocated GMs are distributed to reticulo-endothelial organs.
- This study provides direct evidence of particulate translocation through the M cell pathway, supporting its potential for oral immunization and drug delivery.
