Demonstrates improved localized cancer therapy in digestive tract cancers, suggesting enhanced effectiveness and safety.
Mucoadhesive drug delivery systems (MDDS) improve drug absorption and retention within the gastrointestinal tract by using polymers that bind to the mucosal lining. This prolonged contact increases local drug concentration, enhances bioavailability, and reduces systemic side effects, making the approach particularly effective for colorectal and other digestive tract cancers. By adhering to the mucosa, MDDS extend residence time and can be engineered for targeted release at tumor sites, thereby minimizing toxicity to healthy tissues and overcoming enzymatic barriers that hinder absorption. This study focused on developing mucoadhesive hydrogels embedded with doxorubicin-loaded PLGA nanoparticles (DOX-PLGA NPs) to advance site-specific cancer therapy. The synthesized nanoparticles exhibited a uniform spherical morphology, with an average size of about 97 nm by SEM and a hydrodynamic diameter of 215 nm by DLS, confirming stability with a zeta potential of -30 mV. Incorporating NPs into chitosan hydrogels enhanced porosity, swelling response, and biodegradability, while rheological tests confirmed shear-thinning behavior and improved mechanical resilience-features essential for injectability and mucosal retention. Drug release experiments demonstrated pH-responsive behavior: acidic environments yielded slow, controlled release, while physiological pH triggered faster release. Biological studies indicated that DOX-PLGA hydrogels effectively inhibited cancer cell growth by inducing apoptosis, disrupting mitochondrial function, increasing oxidative stress, and promoting inflammatory markers, alongside glutathione depletion. While chitosan hydrogels alone showed biocompatibility and moderate anticancer activity, the combined nanoparticle-hydrogel system displayed synergistic and superior therapeutic effects. These findings support the potential of this stimuli-responsive platform for precise, localized cancer treatment with reduced systemic toxicity.
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Meng et al. (2026) studied this question.
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