The application of smart pH-sensitive carriers has become an ideal choice for administering drugs with desired release profiles. Although pH-sensitive microbeads offer distinct benefits for delivering anticancer drugs orally, they encounter drawbacks, including low encapsulation efficiency, weak mechanical stability, biocompatibility concerns, and the risk of abrupt release. This study focuses on developing pH-sensitive coated composite microbeads for effective encapsulation and sustained release of 5-fluorouracil (5-FU). Aminated graphene oxide (AmGO) was integrated into carboxymethyl cellulose (CMC) microbeads, which were subsequently coated with an aminated chitosan (AmCs) derivative. Various analysis techniques, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analyzer (TGA), zeta potential (ZP), and mechanical testing, were utilized to characterize the microbeads. The AmCs@CMC@AmGO composite microbeads demonstrated a compact structure with enhanced mechanical properties, achieving a maximum Young's modulus value of 35.99 N/mm2 compared to 25.95 N/mm2 for pure CMC microbeads. Moreover, pH-sensitivity and water uptake studies (at pH 1.2 and pH 7.4) revealed significant tunability of the composite microbeads by altering the AmGO and AmCs ratios. The coated composite microbeads encapsulated approximately 86.4 % of 5-FU compared to 47 % for CMC microbeads. The burst release of 5-FU at pH 7.4 was significantly reduced, with sustained release reaching 51 % over 24 h. The predominant release mechanism was Fickian diffusion, which well-described by the Peppas-Sahlin kinetic model. The developed microbeads exposed improved biodegradability and non-toxicity toward normal colon cells, while exhibiting notable toxicity against cancerous cells, emphasizing its potential for anticancer drug delivery.
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