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Life sciences · Journal article
International Journal of Drug Delivery Technology · October 10, 2026
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Background: Chitosan is an adaptable cationic polysaccharide used to construct nanoparticles for small-molecule, nucleicacid, phototherapeutic, and immunomodulatory cancer interventions.Its apparent simplicity is misleading, because molecular weight, deacetylation, substitution, purity, assembly conditions, and biological medium can change delivery and safety.Objective: This review critically examines recent chitosan nanoparticle advances through a design-mechanismtranslation framework, with emphasis on the validity of targeting claims, causal mechanisms, and clinical readiness.Methods: A structured critical review was conducted using PubMed/MEDLINE, Crossref-verified publisher records, Google Scholar citation chasing, and ClinicalTrials.govfor literature available from 1 January 2020 to 20 June 2026; foundational studies were retained where necessary.Evidence was mapped by material identity, formulation, cargo, route, targeting mechanism, biological model, pharmacology, safety, and development stage.Reporting was appraised using SANRA and MIRIBEL principles.Results: Four conclusions emerged.First, "chitosan nanoparticle" is not an adequate product identity; polymer attributes and process variables must be treated as critical quality attributes.Second, passive access, ligand recognition, stimulus-responsive release, and local retention solve different transport barriers and require different validation experiments.Third, contemporary systems extend beyond chemotherapy to RNA interference, CRISPR-associated delivery, photoimmunotherapy, radiosensitization, and tumor-immune modulation, but mechanistic claims frequently rely on downstream cytotoxicity rather than exposure, release, and target-engagement evidence.Fourth, clinical translation remains limited.PRV111 provides early peer-reviewed proof of local cisplatin delivery in oral cancer, whereas later PRV211 observations remain preliminary and non-peer-reviewed.Conclusion: Chitosan nanomedicines are most credible when a defined material and route address a specific clinical barrier, targeting is causally validated, pharmacokinetics and immunotoxicity are quantified, and manufacture is scalable.Added multifunctionality should be justified by measurable, nonredundant benefit rather than formulation novelty alone.