Box-Behnken optimization of stimuli-responsive DOX@Ag-MOF/chitosan - Polycaprolactone nanofiber membranes for smart controlled drug delivery and multifunctional therapeutic applications.

Metal-organic frameworks (MOFs) have gained recognition as viable candidates for developing targeted and stimuli-responsive drug delivery systems. In the present study, we constructed a multifunctional drug delivery platform by integrating the anticancer agent doxorubicin (DOX) within a silver-based MOF (Ag-MOF). This encapsulation was subsequently followed by incorporating the composite into electrospun nanofiber membranes formulated from chitosan (CS) and polycaprolactone (PCL). The resultant DOX@Ag-MOF nanofiber membrane was produced using a one-pot electrospinning method and was subjected to extensive characterization employing techniques such as FTIR, XRD, SEM, XPS, EDX, and nitrogen adsorption-desorption isotherms. The drug release characteristics were methodically analyzed in response to different external factors such as pH, temperature, and time. The nanofiber membrane demonstrated a pH-responsive release profile, with a notable increase in drug diffusion observed in acidic environments (pH 5.0), effectively replicating conditions found in tumor microenvironments, as opposed to release at physiological pH levels (6.2 and 7.4). Furthermore, the investigation revealed that drug release was positively correlated with temperature, achieving peak efficacy at 37 °C. The kinetic analysis of release data revealed that the system operates under several release mechanisms, specifically adhering to zero-order, first-order, Higuchi, and Korsmeyer-Peppas models. Additionally, the DOX@Ag-MOF nanofiber demonstrated significant anticancer effects against various tumor cell lines, including those associated with breast, liver, and skin cancers. Moreover, this nanofiber displayed robust antioxidant and antimicrobial activities against pathogens such as E. coli, Staphylococcus aureus, and Candida albicans. These results underscore the potential utility of this hybrid nanofiber system as a multifaceted platform for controlled drug delivery, cancer treatment, and broader biomedical applications. The study further suggests the need for optimization of conditions through the Box-Behnken design methodology.