ISSN 1866-8836
Клеточная терапия и трансплантация

BS-01. Prospects for the use of polymer and polymer-modified structure particles in approaches to gene therapy of diseases of the gastrointestinal tract

Darya R. Akhmetova, Anna S. Rogova, Alice S. Postovalova, Alexandra V. Brodskaya

Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia


Contact: Darya R. Akhmetova, e-mail: ahmetova.darya1999@yandex.ru

doi 10.18620/ctt-1866-8836-2023-12-3-1-176

Summary

Despite rapid development of modern methods, there is an urgent need for new therapeutic agents for the treatment of gastrointestinal diseases. The field of gene therapy has long gone beyond the correction of hereditary genetic pathologies and actively demonstrates approaches to the impact on acquired diseases, such as oncology and inflammatory processes, using targeted microRNA delivery. The purpose of this work is to study the prospects for the use of micro- and nanocarriers CaCO3 and polyacrylic acid (PLA) in oral administration, their pharmacokinetics and interaction with the gastrointestinal tract.

Materials and methods

The study employed CaCO3 micro- and nanoparticles obtained by co-precipitation of salt aqueous solutions(sodium carbonate and calcium chloride) with the addition of polymers (polyarginine/Dextran sulfate (PARG/DEXS) by the later-by-layer method for microparticles and polyacrylic acid (PAA) for nanoparticles added as stabilizeing agent during the synthesis. Micro- and nanoparticles of PLA (mPLA and nPLA, respectively) obtained by the double emulgation method were also used as polymer carriers. Interaction with model intestinal epithelial cells (Caco2) was studied by means of flow cytometry, as well as by confocal laser scanning microscopy (CLSM), while staining the particles with Cy5 fluorescent dye (red), labeling the cells with AlexaFluor 488 (membranes, green) and Doxorubicin (nuclei, blue). The bio-distribution of particles was evaluated by ex vivo fluorescence imaging (BalB/c mice, 5 groups in triplicate).

Results

During this study, the synthesized particles of polymer and polymer-modified structure showed a high degree of interaction with Caco2 cells according to the results of flow cytometry (74.2% for mCaCO3, 83.6% for mCaCO3, 94.8% for mPLA, 100% for nPLA). The obtained KLSM images confirm not only an association with cells, but also the active capture of particles and their localization in the region of the cell nucleus (Fig. 1A). The ex vivo study of the particles’ bio-distribution after oral administration showed an active accumulation of particles in the stomach and colon, as well as adsorption in the walls of the small intestine in the case of nPLA (Fig. 1B).

Conclusion

As a result of our studies, the particles of polymer and polymer-modified structure based on CaCO3 and PLA have proved to be promising platforms for targeted delivery of microRNA in gastric cancer, colorectal cancer, inflammatory bowel diseases, as well as in gene therapy of rotavirus infection affecting mucous membranes of the small intestine.

Acknowledgments

The research was carried out with the financial support of the Russian Academy of Sciences within the framework of scientific project No. 22-74-10117 of the Presidential Program of Research Projects implemented by leading scientists, including young scientists.

Keywords

Microparticles, nanoparticles, calcium carbonate, polymers, gene therapy, microRNA.


Akhmetova-fig01.jpg

Figure 1. A) CLSM image of Caco2 cells uptake of nPLA particles; B) Particles fluorescense from main organs of GIT

Supplement 12-3
09/30/2023

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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