DEVELOPMENT AND OPTIMIZATION OF ESCULETIN LOADED FUNCTIONALIZED MESOPOROUS SILICA NANOPARTICLES FOR TARGETED DELIVERY IN COLORECTAL CANCER

Abstract

Objectives: To develop and optimize esculetin-loaded functionalized mesoporous silica nanoparticles (MSN-ESC-COOH) for targeted delivery in colorectal cancer using Box-Behnken factorial design, addressing esculetin's poor aqueous solubility and limited bioavailability.

Methods: Mesoporous silica nanoparticles (MSNs) were synthesized by a modified sol-gel method using CTAB, TEOS, and TEA. CTAB concentration (0.50–0.75 g), TEOS volume (7.5–10.0 mL) and TEA volume (1.5–2.5 mL) were optimalized using a three-factor, three-level Box-Behnken design to minimize the size of particles obtained and to maximize their entrapping efficiency. The optimized composition was characterized and the results are shown}. To extensively characterize the compounds, FTIR; differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD); field emission scanning electron microscopy (FESEM); dynamic light scattering (DLS); zeta potential determination; in vitro release kinetics and MTT cytotoxicity assay against HCT-116 colorectal cancer cells.

Results: A total of 17 formulations were optimized with a particle size and entrapment efficiency in the ranges of 102.4–214.3 nm and 53.4–82.4%, respectively. ANOVA indicated CTAB was the most significant factor (F = 325.38 for particle size; F = 264.25 for entrapment efficiency, p < 0.0001). Formulation DF9 was found optimal having particle size 102.4 ± 2.9 nm, PDI 0.188, zeta potential −30.2 ± 1.1 mV and entrapment efficiency (EE) as 82.4 ± 1.4% with desirability of 1,000 FTIR and PXRD confirm successful functionalization and drug amorphization. Release was controlled biphasic (72.4% at 12h) followed Korsmeyer-Peppas kinetics (n = 0.9038). MSN-ESC-COOH exhibited 1.81-fold improved cytotoxicity (IC₅₀ = 21.38 μg/mL) compared to pure esculetin (IC₅₀ = 38.64 μg/mL) at minimal carrier toxicity.

Conclusion: Here we demonstrate an optimized MSN-ESC-COOH nanoformulation as a potential targeted delivery platform for colorectal cancer therapy, with translational applicability meriting further in vivo evaluation of pharmacokinetics and efficacy.