Application of chitosan/alginate nanoparticle in oral drug delivery systems: prospects and challenges

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Abstract

Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.

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Most cited references 68

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Ulcerative colitis

Taku Kobayashi, Britta Siegmund, Catherine Le Berre … (2020)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. UC has evolved into a global burden given its high incidence in developed countries and the substantial increase in incidence in developing countries. An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. Since the early 2000s, anti-tumour necrosis factor (TNF) treatment has significantly improved treatment outcomes. Advances in medical treatments have enabled a paradigm shift in treatment goals from symptomatic relief to endoscopic and histological healing to achieve better long-term outcomes and, consequently, diagnostic modalities have also been improved to monitor disease activity more tightly. Despite these improvements in patient care, a substantial proportion of patients, for example, those who are refractory to medical treatment or those who develop colitis-associated colorectal dysplasia or cancer, still require restorative proctocolectomy. The development of novel drugs and improvement of the treatment strategy by implementing personalized medicine are warranted to achieve optimal disease control. However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.

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Acidic extracellular microenvironment and cancer

Yasumasa Kato, Shigeyuki Ozawa, Chihiro Miyamoto … (2013)

Acidic extracellular pH is a major feature of tumor tissue, extracellular acidification being primarily considered to be due to lactate secretion from anaerobic glycolysis. Clinicopathological evidence shows that transporters and pumps contribute to H+ secretion, such as the Na+/H+ exchanger, the H+-lactate co-transporter, monocarboxylate transporters, and the proton pump (H+-ATPase); these may also be associated with tumor metastasis. An acidic extracellular pH not only activates secreted lysosomal enzymes that have an optimal pH in the acidic range, but induces the expression of certain genes of pro-metastatic factors through an intracellular signaling cascade that is different from hypoxia. In addition to lactate, CO2 from the pentose phosphate pathway is an alternative source of acidity, showing that hypoxia and extracellular acidity are, while being independent from each other, deeply associated with the cellular microenvironment. In this article, the importance of an acidic extracellular pH as a microenvironmental factor participating in tumor progression is reviewed.

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Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers.

Laura Ensign, Richard Cone, Justin Hanes (2012)

Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the continuous secretion of mucus that protects the GI tract. Nanoparticle drug carriers that can shield drugs from degradation and deliver them to intended sites within the GI tract may enable more efficient and sustained drug delivery. However, the rapid secretion and shedding of GI tract mucus can significantly limit the effectiveness of nanoparticle drug delivery systems. Many types of nanoparticles are efficiently trapped in and rapidly removed by mucus, making controlled release in the GI tract difficult. This review addresses the protective barrier properties of mucus secretions, how mucus affects the fate of orally administered nanoparticles, and recent developments in nanoparticles engineered to penetrate the mucus barrier. Copyright © 2011 Elsevier B.V. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Drug Deliv

Journal ID (iso-abbrev): Drug Deliv

Title: Drug Delivery

Publisher: Taylor & Francis

ISSN (Print): 1071-7544

ISSN (Electronic): 1521-0464

Publication date (Electronic, pub): 6 April 2022

Publication date (Electronic, collection): 2022

Publication date PMC-release: 6 April 2022

Volume: 29

Issue: 1

Pages: 1142-1149

Affiliations

[a ]School of Basic Medicine, Qingdao Medical College, Qingdao University , Qingdao, China

[b ]Molecular Cancer Biology Laboratory, Cellular Heterogeneity Research Center, Department of Biosystem, Sookmyung Women’s University , Seoul, Korea

[c ]Institute of Applied Sciences, Ho Chi Minh City University of Technology HUTECH , Ho Chi Minh City, Viet Nam

[d ]Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resource , Qingdao, China

Author notes

*These authors have contributed equally to this work and share first authorship.

CONTACT Myeong-Sok Lee mslee@ 123456sookmyung.ac.kr Molecular Cancer Biology Laboratory, Cellular Heterogeneity Research Center, Department of Biosystem, Sookmyung Women’s University , Seoul, Korea

Zhou Zheng zhengzhou@ 123456fio.org.cn Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resource , Qingdao, China

Article

Publisher ID: 2058646

DOI: 10.1080/10717544.2022.2058646

PMC ID: 9004504

PubMed ID: 35384787

SO-VID: 341631bf-d70e-4313-9c24-ffc2627bb299

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Application of chitosan/alginate nanoparticle in oral drug delivery systems: prospects and challenges

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RNA drug delivery

Most cited references 68

Ulcerative colitis

Acidic extracellular microenvironment and cancer

Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers.

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