Cited by 127Advanced Drug Delivery SystemsNanoparticle-Based Drug DeliveryDrug Solubulity and Delivery Systems

The DOI matches its Crossref record; 220 of the 220 references it cites were found in a registry or an index; 12 of the 187 sources its claims cite were checked for support.

Current Advances in Chitosan Nanoparticles Based Oral Drug Delivery for Colorectal Cancer Treatment

Open access

Abstract

As per the WHO, colorectal cancer (CRC) caused around 935,173 deaths worldwide in 2020 in both sexes and at all ages. The available anticancer therapies including chemotherapy, radiotherapy and anticancer drugs are all associated with limited therapeutic efficacy, adverse effects and low chances. This has urged to emerge several novel therapeutic agents as potential therapies for CRC including synthetic and natural materials. Orally administrable and targeted drug delivery systems are attractive strategies for CRC therapy as they minimize the side effects, enhance the efficacy of anticancer drugs. Nevertheless, oral drug delivery till today faces several challenges like poor drug solubility, stability, and permeability. Various oral nano-based approaches and targeted drug delivery systems have been developed recently, as a result of the ability of nanoparticles to control the release of the encapsulant, drug targeting and reduce the number of dosages administered. The unique physicochemical properties of chitosan polymer assist to overcome oral drug delivery barriers and target the colon tumour cells. Chitosan-based nanocarriers offered additional improvements by enhancing the stability, targeting and bioavailability of several anti-colorectal cancer agents. Modified chitosan derivatives also facilitated CRC targeting through strengthening the protection of encapsulant against acidic and enzyme degradation of gastrointestinal track (GIT). This review aims to provide an overview of CRC pathology, therapy and the barriers against oral drug delivery. It also emphasizes the role of nanotechnology in oral drug targeted delivery system and the growing interest towards chitosan and its derivatives. The present review summarizes the relevant works to date that have studied the potential applications of chitosan-based nanocarrier towards CRC treatment.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes oral chitosan-based nanoparticle strategies for colorectal cancer (CRC), covering CRC pathology, oral delivery barriers, chitosan derivatives, and passive/active targeting. It reports that chitosan and modified chitosan nanocarriers can improve stability, mucoadhesion, colon targeting, and anticancer efficacy, but human efficacy remains unestablished.

Key findings

  • CRC caused around 935,173 deaths worldwide in 2020; regional deaths were 506,449 in Asia, 244,824 in Europe, 63,987 in North America, and 69,435 in Latin America and the Caribbean, with morbidity expected to reach 1.1 million worldwide by 2030. Stage I–II 5-year survival is 37–74%, dropping to 6% in advanced stages.
  • Chitosan-based nanoparticles (CSNPs) are reported to overcome oral delivery barriers through cationic mucoadhesion, transient tight-junction opening, and biodegradation by colonic microflora; modified derivatives such as trimethyl chitosan, carboxymethyl chitosan, N-succinyl-chitosan, hyaluronic acid-, PEG-, and folic acid-conjugated chitosan enhance solubility, targeting, and circulation.
  • In summarized studies, chitosan-cellulose 5-fluorouracil nanoparticles released 42.37 ± 0.43% at pH 1.2 and 76.82 ± 1.29% at pH 7.4; at 250 µg/mL they eliminated 8.16 ± 2.11% of CCD112 normal cells versus 56.42 ± 0.41% of HCT-116 cancer cells. Mesoporous silica nanoparticles coated with folic acid chitosan-glycin complex showed 4% toxicity against normal cells versus 60% for colchicine alone.
  • Chitosan-based siRNA delivery protected siRNA and reduced β-catenin protein to around 40.10% in HT-29 cells; carboxymethyl dextran-CSNPs delivering snail siRNA and doxorubicin altered EMT genes and inhibited HCT-116 growth, migration, and induced apoptosis.

Methods

  • Narrative review; no systematic review protocol or meta-analysis is stated. It synthesizes literature on CRC pathology and therapy, oral drug delivery barriers, nanotechnology, chitosan and its derivatives, and CSNPs for CRC and siRNA delivery.
  • Data/sample: published studies and tables summarizing chitosan-based nanoparticle formulations, active compounds, nanoparticle characteristics (e.g., particle size, zeta potential, encapsulation efficiency), cell lines, and outcomes, including Tables 4, 5, and 6.
  • Main analysis: qualitative synthesis and tabulation of preclinical in vitro and in vivo findings; no primary experiments are reported.

Limitations

  • The paper states that toxicity and immunogenicity of chitosan nanocarriers toward more normal cell lines need to be studied, particularly for long-term effects, and that approaches have yet to progress beyond animal studies and establish relevant efficacy in humans.
  • Evident from the text: as a narrative review, it provides no primary data or systematic quality assessment; included studies vary in cell lines, formulations, and outcome measures, and some table entries are incomplete (e.g., targeted receptor listed as “-”).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.2147/ijn.s375229

Cites

220 of 220 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Figure 1 Examples of nanoparticles used in the therapeutic management of colorectal cancer.
Figure 1 Examples of nanoparticles used in the therapeutic management of colorectal cancer.CC BY-NC · PubMed Central
Figure 2 Deacetylation of chitin into chitosan.
Figure 2 Deacetylation of chitin into chitosan.CC BY-NC · PubMed Central
Figure 3 Schematic illustration of the interaction between chitosan loaded nanoparticles with the mucus layer.
Figure 3 Schematic illustration of the interaction between chitosan loaded nanoparticles with the mucus layer.CC BY-NC · PubMed Central
Figure 4 Synthesis of N,N,N-trimethyl chitosan.
Figure 4 Synthesis of N,N,N-trimethyl chitosan.CC BY-NC · PubMed Central
Figure 5 Synthesis of N,O-carboxymethyl chitosan.
Figure 5 Synthesis of N,O-carboxymethyl chitosan.CC BY-NC · PubMed Central
Figure 6 Chemical structure of N-succinyl-chitosan.
Figure 6 Chemical structure of N-succinyl-chitosan.CC BY-NC · PubMed Central
Figure 7 Possible chemical structure of hyaluronic acid (HA)-conjugated chitosan (CS).
Figure 7 Possible chemical structure of hyaluronic acid (HA)-conjugated chitosan (CS).CC BY-NC · PubMed Central
Figure 8 Chemical structure of PEG-conjugated chitosan.
Figure 8 Chemical structure of PEG-conjugated chitosan.CC BY-NC · PubMed Central
Figure 9 Chemical structure of folic acid-conjugated chitosan.
Figure 9 Chemical structure of folic acid-conjugated chitosan.CC BY-NC · PubMed Central

Verification

Claims the paper makes

72 No full text of the sources · 68 Not checked yet · 53 No basis given · 20 Own interpretation · 5 Supported · 3 Partly supported · 2 Supported so far · 1 Check pending · accuracy not yet measured

Verify all 76 references — free account

Show all 84 claims

  • It may state two separate claims as one. 90
  • Probably not a substantial claim. 77
140 of 140
  • The paper relies on this without support.

    Results from in vitro and animal studies of chitosan-based nanocarriers are predictive of clinical benefit in human CRC patients.

    “CSNPs are considered a very promising strategy to overcome the low stability and bioavailability of many active ingredients.”
    “In 2021, Wang and his team combined of oxaliplatin and resveratrol successfully into N,O-carboxymethyl chitosan nanoparticles as a promise strategy for colorectal cancer therapy.”
  • The paper relies on this without support.

    In vitro CRC cell lines (e.g., HT-29, HCT-116) are valid models for predicting clinical anti-CRC efficacy in humans.

    “Coated NPs showed significant inhibition of colon cancer cells (HT-29) compared to uncoated NPs or free drug solution.38”
    “The inhibition efficiency and anti-colon cancer activity of the combined treatment were more stronger than either type of nanoparticle alone or the free drugs.43”
  • The paper relies on this without support.

    The pH of the gastrointestinal tract denatures or depurinates most orally administered drugs and substantially reduces their effectiveness.

    “The pH is the first biological barrier to any orally delivered drug, which denature/depurination most of the administered drugs and substantially reduces their effectiveness.”
  • The paper relies on this without support.

    Enzymatic degradation of dosage forms and drugs occurs throughout the gastrointestinal tract and affects their stability.

    “Enzymatic degradation of dosage forms and drugs can occur throughout the GIT and hence can affect their stability.”
  • The paper relies on this without support.

    PEG chains prevent adhesion of opsonins in blood by forming a barrier layer around particles that is invisible to phagocytic cells.

    “PEG chains prevent the adhesion of opsonins existing in the blood by generating a barrier layer surrounding the particles that can be “invisible” to phagocytic cells.”
  • The paper relies on this without support.

    Folate receptors are among the most expressed receptors on many cancer cell types, and their expression is limited in normal cells.

    “Folate receptors are considered as one of the most expressed among receptors on many cancer cells types, besides, their expression levels are limited in normal cells.”
  • The paper relies on this without support.

    Targeted delivery of siRNA faces low intracellular uptake and rapid degradation.

    “However, the targeted delivery of siRNA has faced several challenges, including low intracellular uptake and rapid degradation.”
  • The paper relies on this without support.

    The degree of quaternization increases the permeation-enhancing effect of trimethyl chitosan.

    “In addition, the degree of quarternization increases the permeation-enhancing effect.”
8 of 8

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

3 of 3

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

1 of 1

Citations

Cites

1 retracted

Show all 220 references

Research works printed but not linked: 10

  1. Tian, 2018, J Buon, 23, 1331
  2. Prasanth, 2012, J Appl Pharm Sci, 2, 163
  3. Armaghany, 2012, Gastrointest Cancer Res, 5, 19
  4. Grothey, 2019, Clin Adv Hematol Oncol, 17, 16
  5. Su, 2006, Anticancer Res, 26, 4379
  6. 2018, Goodman & Gilman’s: The Pharmacological Basis of Therapeutics
  7. 2020, Handbook of Chitin and Chitosan
  8. 2019, Encyclopedia of Biomedical Engineering
  9. Raizaday, 2015, Cell Chem Technol, 49, 41
  10. Guo, 2015, Drug Res, 65, 199

Cited by

Sorted by citations

Metadata

Authors
Choukaife, H., Seyam, S., Alallam, B., Doolaanea, A. A., & Alfatama, M.
Affiliations
  • Sultan Zainal Abidin University (MY)
  • Universiti Sains Malaysia (MY)
  • International Islamic University Malaysia (MY)
Corresponding author
Alfatama, Mulham
Venue
International Journal of Nanomedicine
Published
2022-09
Volume
Volume 17
Pages
3933-3966
ISSN
  • 1176-9114 (ISSN-L)
  • 1178-2013
OpenAlex
W4294762977
Cited by
127
References
220
Citations by year
2026: 34 · 2025: 39 · 2024: 29 · 2023: 25
FWCI
1.96
Type
journal article
Language
en
Open access
Locations
  • International Journal of Nanomedicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders
Universiti Sultan Zainal Abidin
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords
chitosan nanoparticles, colorectal cancer, oral drug delivery, targeted drug delivery, chitosan derivatives, nanocarriers, colon-targeted drug delivery, bioavailability, anticancer drug delivery
MeSH terms
Antineoplastic Agents, Neoplasms, Drug Delivery Systems, Nanotechnology, Chitosan, Nanoparticles

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