Steric and Energetic Characterization of Advanced Glauconite Based Silicate Nanosheets and Nano-Rods as Deliveries of Cisplatin Chemotherapy: Loading, Release, and Anticancer Activities

Abstract

Natural glauconite (GN) underwent facile exfoliation and scrolling modifications, resulting in two advanced structural derivatives with distinct morphologies: exfoliated glauconite nanosheets (Si-EXGN) and silicate nanorods (Si-GNRs). These derivatives exhibited enhanced physicochemical properties and were evaluated as both anticancer agents and delivery systems for cisplatin (CSPL). Compared to raw GN (119.3 mg/g), the modified derivatives exhibited significantly higher CSPL loading capacities: 309.4 mg/g for GNRs and 202.4 mg/g for EXGN. The loading behaviors were well-described by pseudo-first-order kinetics (R² > 0.94) and Langmuir isotherms (R² > 0.99). Advanced isotherm modeling highlighted the enriched interfaces of GNRs with a higher active site density (50.64 mg/g) compared to EXGN (38.4 mg/g) and GN (26.3 mg/g), allowing each GNR site to accommodate up to 7 CSPL molecules versus 5 for EXGN and 4 for GN. The loading process, governed by multimolecular physical interactions, was validated through loading energy values (<11 kJ/mol). The CSPL release profiles from EXGN and GNRs were continuous and prolonged, achieving 97.8% release after 200 hr and 100% release after 110 hr at physiological pH (7.4), respectively. Kinetic modeling revealed that the release process followed a non-Fickian transport mechanism, regulated primarily by diffusion and erosion. Specifically, release kinetics adhered to first-order (R² > 0.91–0.99), Hixson-Crowell (R² = 0.85–0.96), and Higuchi models (R² = 0.80–0.89). As standalone agents, EXGN (cell viability = 36.2%; IC50 = 230 µg/mL) and GNRs (cell viability = 22.4%; IC50 = 189.7 µg/mL) exhibited notable anticancer effects against human cervical cancer (HeLa) cells. Furthermore, when utilized as carriers for CSPL, their therapeutic efficacy was significantly enhanced. The CSPL-loaded EXGN system reduced cell viability to 2.3% (IC50 = 5.4 µg/mL), while the CSPL-loaded GNRs achieved superior cytotoxicity with a cell viability of 0.87% (IC50 = 1.6 µg/mL). The study underscores the potential of Si-EXGN and Si-GNRs as highly efficient drug delivery systems and anticancer agents. However, further in-depth in vivo evaluations are recommended to confirm the safety and biocompatibility of these materials.