Impact of physico-chemical properties of non-viral nucleic acid nano- and microcarriers on oral delivery: Current status and Challenges



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Abstract

Oral delivery of nucleic acid (NA) therapeutics offers a promising, non-invasive approach for treating gastrointestinal (GI) diseases such as inflammatory bowel disease (IBD), colorectal cancer (CRC), and infections, as well as systemic conditions like diabetes and hemophilia. However, the gastrointestinal tract (GIT) presents significant barriers, including harsh pH, enzymatic degradation, and mucosal layers, which challenge the stability, bioavailability, and targeting of NAs. This review explores the impact of physico-chemical properties of non-viral nano- and microcarriers on overcoming these barriers for effective oral NA delivery. We discuss various carrier systems, including polymeric, lipid-based, and metal-organic frameworks (MOFs), focusing on their design strategies for site-specific delivery to the stomach, small intestine, and colon. Key advancements, such as mucoadhesive and pH-responsive carriers, are highlighted alongside in vivo studies demonstrating their efficacy in preclinical models. Despite progress, challenges in scalability, regulatory approval, and clinical translation remain. This review underscores the potential of optimized NA delivery systems to transform clinical practice while identifying future directions for research and development.

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About the authors

Rime Hafsa Djazouli

Peter the Great St. Petersburg Polytechnic University

Email: dzhazuli.rh@edu.spbstu.ru
ORCID iD: 0009-0004-9861-1631
Russian Federation, Politekhnicheskaya Ulitsa, 29, St Petersburg, 195251

Darya R Akhmetova

Peter the Great St. Petersburg Polytechnic University; ITMO University

Email: akhmetova.lab.dr@gmail.com
ORCID iD: 0009-0003-2808-4795
Russian Federation, Politekhnicheskaya Ulitsa, 29, St Petersburg, 195251;Kronverkskiy Prospekt, 49, St Petersburg, 197101

Anna S Rogova

Peter the Great St. Petersburg Polytechnic University

Email: anna.aroo@mail.ru
ORCID iD: 0000-0001-5116-9007
Russian Federation, Politekhnicheskaya Ulitsa, 29, St Petersburg, 195251

Alexandra V Brodskaia

Peter the Great St.Petersburg Polytechnic University;
Smorodincev Research Institute of Influenza

Author for correspondence.
Email: Alexandra.b_05@mail.ru
ORCID iD: 0000-0001-5130-3755

Доцент ВШБСиТ

Институт Биомедицинских Систем и Биотехнологий

Politekhnicheskaya Ulitsa, 29, St Petersburg, 195251;197022 St. Petersburg st. prof. Popova 15/17

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