pH-responsive acetylated PAMAM dendrimer nanocarriers for enhanced intravesical delivery of Erdafitinib in urothelial carcinoma

Urothelial carcinoma, the most frequent type of bladder cancer, is associated with high recurrence and low efficacy of standard treatments. Erdafitinib, an FGFR inhibitor, has therapeutic potential but is limited by systemic toxicity, poor tumor selectivity, and unpredictable pharmacokinetics. The objective of the research to design and evaluate acetylated poly(amidoamine) (PAMAM G0) dendrimer nanocarriers (AC-PAMAM-ERB) for the enhanced intravesical administration of erdafitinib. A two-level fractional factorial design used to optimize the formulation. The optimized formulation had a particle size of 246.6 ± 3.9 nm, a zeta potential of − 22.5 ± 0.14 mV, and a high encapsulation efficiency of 95.93 ± 3.21%, SEM showed that the particles were spherical. In vitro release experiments showed that the drug was released slowly and in a way that depended on the pH. At acidic pH, 77.96 ± 4.7%, of the drug was released, which was consistent with first-order kinetics and non-Fickian diffusion. The invitro cytotoxicity test on T24 bladder cancer cells demonstrated that AC-PAMAM-ERB possessed significantly greater potency (IC₅₀ = 84.11 ± 0.03 µg/mL) compared to free erdafitinib (IC₅₀ = 96.11 ± 0.05 µg/mL), showing a 1.14-fold higher potency than free erdafitinib (p < 0.05). These in vitro findings confirm that acetylated PAMAM dendrimers represent a promising nanocarrier platform for the intravesical delivery of erdafitinib, prompting additional research. The formulation exhibits pH-responsive release and increased cytotoxicity, indicating its potential for localized therapy, which warrants validation through future in vivo studies.