Folate‐Modified Drug‐Carrying Micelles With <scp>pH</scp>‐Responsiveness for Curcumin‐Targeted Delivery

ABSTRACT A predrug delivery system combining tumor‐targeting and pH‐responsive features was synthesized using baicalin (BAI), polyethylene glycol (PEG), and folic acid (FA). BAI and PEG were linked via esterification to create pH‐sensitive ester bonds (COO) that facilitate drug release in acidic environments, while FA was attached to PEG through substitution. This system, named FA‐PEG‐COO‐BAI (FPB), encapsulated curcumin (CUR) to form drug‐loaded micelles. The impact of drug‐loading conditions, such as sonication duration and initial drug dosage, on CUR/FA‐PEG‐COO‐BAI encapsulation efficiency and drug release was investigated. In vitro studies demonstrated a maximum encapsulation rate of (73.09 ± 3.31)% and a drug‐loading rate of (11.90 ± 0.69)%. Drug release from CUR/FA‐PEG‐COO‐BAI micelles accelerated as pH decreased, confirming pH‐responsive behavior. Cellular uptake and antitumor assays suggested effective tumor targeting and inhibition of proliferation. Hemolysis and cell viability assays indicated low toxicity. These findings underscore the potential of CUR/FA‐PEG‐COO‐BAI micelles for controlled drug release and targeted therapy.