2 research outputs found
Enhanced delivery of anti-inflammatory therapeutics using pH-responsive histidine-modified poly-L-lysine on mesoporous silica nanoparticles
No full textMesoporous silica nanoparticles (MSNs) are effective platforms for drug delivery due to their high surface area, adjustable pore sizes, and biocompatibility. The aim of this study was to explore the application of histidine-modified poly-L-lysine (PLL-His) as a pH-responsive gatekeeper to control the release of an anti-inflammatory agent, celecoxib, from MSNs. MSNs were synthesized through a sol-gel process using cetyltrimethylammonium bromide (CTAB) as a template and were functionalized with amine groups using (3-aminopropyl)triethoxysilane (APTES). Drug loading was achieved via adsorption in ethanol. Subsequently, poly-L-lysine (PLL) and PLL-His were conjugated to the MSNs using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) and N-hydroxysuccinimide (NHS) to form MSN-NH2-Drug-PLL and MSN-NH2-Drug-PLL-His constructs. Characterization of these particles was conducted using Fourier-transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) analysis, and particle size analysis. Results showed that the particle size of MSN-NH2-drug-PLL and MSN-NH2-drug-PLL-His was 237.10±6.56 nm and 234.03±14.65 nm, respectively, indicating suitability for cellular uptake. BET analysis confirmed the increased surface area and pore volume after the removal of CTAB, demonstrating successful mesopore formation. Drug release tests were performed in simulated gastric (pH 1.2) and physiological (pH 7.4) conditions, showing that PLL-His-modified MSNs exhibited minimal release in acidic conditions and sustained release at physiological pH. The PLL-His effectively functioned as a pH-responsive gatekeeper, enhancing drug targeting and reducing premature release. This study highlights the potential of PLL-His-modified MSNs as a promising model for pH-sensitive, targeted drug delivery, with potential applications across various therapeutic areas requiring precise release profiles. This approach could significantly improve therapeutic outcomes and patient compliance, particularly in disease contexts where pH variability is a critical factor. Overall, the integration of PLL-His as a pH-responsive gatekeeper represents a significant advancement in the design of smart drug delivery systems
Dual-Functionalized Mesoporous Silica Nanoparticles for Celecoxib Delivery: Amine Grafting and Imidazolyl PEI Gatekeepers for Enhanced Loading and Controlled Release with Reduced Toxicity
No full textThe development of targeted drug delivery systems has been a pivotal area in nanomedicine, addressing challenges like low drug loading capacity, uncontrolled release, and systemic toxicity. This study aims to develop and evaluate dual-functionalized mesoporous silica nanoparticles (MSN) for targeted delivery of celecoxib, enhancing drug loading, achieving controlled release, and reducing systemic toxicity through amine grafting and imidazolyl polyethyleneimine (PEI) gatekeepers. MSN were synthesized using the sol–gel method and functionalized with (3-aminopropyl) triethoxysilane (APTES) to create amine-grafted MSN (MSN-NH2). Celecoxib was loaded into MSN-NH2, followed by conjugation of imidazole-functionalized PEI (IP) gatekeepers synthesized via carbodiimide coupling. Characterization was conducted using Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR). Drug loading capacity, entrapment efficiency, and in vitro drug release at pH 5.5 and 7.4 were evaluated. Cytotoxicity was assessed using the MTT assay on RAW 264.7 macrophages. The synthesized IP was confirmed by FTIR and 1H-NMR. Amine-grafted MSN demonstrated a celecoxib loading capacity of 12.91 ± 2.02%, 2.1 times higher than non-functionalized MSN. In vitro release studies showed pH-responsive behavior with significantly higher celecoxib release from MSN-NH2-celecoxib-IP at pH 5.5 compared to pH 7.4, achieving a 33% increase in release rate within 2 h. Cytotoxicity tests indicated significantly higher cell viability for IP-treated cells compared to PEI-treated cells, confirming reduced toxicity. The dual-functionalization of MSN with amine grafting and imidazolyl PEI gatekeepers enhances celecoxib loading and provides controlled pH-responsive drug release while reducing systemic toxicity. These findings highlight the potential of this advanced drug delivery system for targeted anti-inflammatory and anticancer therapies
