ph-responsive cyclodextrin nanosponges for drugdelivery

Smart drug delivery systems offer significant advantages in cancer treatment. The tumormicroenvironment's acidified pH, caused by cancer cell metabolism, provides a uniqueopportunity to exploit pH-responsive therapies.In this thesis, pH-responsive cyclodextrin nanosponges (CD NSs) were synthesized forthe first time for drug delivery applications. β-cyclodextrin (β-CD) was oxidized andcrosslinked with adipic acid dihydrazide (ADH) to produce NSs containing acid-sensitive hydrazone bonds, designed to cleave in acidic conditions. These NSs were used fordoxorubicin delivery, with additional functionalization using folic acid to enhanceselective uptake by cancer cells.Comprehensive characterization techniques, including FTIR, ¹H-NMR, DLS, zetapotential measurements, UV-Vis, TGA, DSC, XRD, SEM, and TEM, confirmedsuccessful β-CD oxidation, NS formation, drug loading, and folic acid conjugation. TheNSs exhibited an amorphous structure, spherical morphology, uniform size distribution,and minimal surface charge. These NSs were thermally stable, having doxorubicinencapsulation efficiency (EE) of 58% and showed a 1.5-fold increase in drug releaseunder acidic conditions compared to neutral pH.Biological tests demonstrated that blank NSs were non-toxic to MCF-7 breast cancer cellsand L929 fibroblast cells. Doxorubicin-loaded NSs (NS-Dox) induced selectivecytotoxicity in MCF-7 cells while sparing L929 cells from the harmful effects. FAconjugation significantly enhanced therapeutic efficacy by reducing the IC50 value of NSDox.Cellular uptake studies confirmed that doxorubicin encapsulation in NSssubstantially improved internalization by MCF-7 cells.These findings highlight the potential of the synthesized pH-responsive NSs as effectiveand targeted delivery vehicles for cancer therapy, offering a promising alternative toconventional treatments.