A pH-sensitive silica nanoparticles for colon-specific delivery and controlled release of catechin: Optimization of loading efficiency and in vitro release kinetics.

Catechin is a naturally occurring flavonoid of the flavan-3-ol subclass with numerous biological functions; however, these benefits are diminished due to several factors, including low water solubility and degradation in the stomach's harsh environment. So, this study aimed to develop an intelligent catechin colon-targeting delivery system with a high loading capacity. This was done by coating surface-decorated mesoporous silica nanoparticles with a pH-responsive enteric polymer called Eudragit®-S100. The pristine wormlike mesoporous silica nanoparticles (< 100 nm) with high surface area and large total pore volume were effectively synthesized and modified with the NH2 group using the post-grafting strategy. Various parameters, including solvent polarity, catechin-carrier mass ratio, and adsorption time, were studied to improve the loading of catechin into the aminated silica nanoparticles. Next, the negatively charged Eudragit®-S100 was electrostatically coated onto the positively charged aminated nanocarriers to shield the loaded catechin from the acidic environment of the stomach (pH 1.9) and to facilitate site-specific delivery in the acidic environment of the colon (pH 7.4). The prepared nanomaterials were evaluated using several methods, including The Brauner-Emmett-Teller, surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope, Powder X-Ray Diffraction, Fourier Transform Infrared Spectroscopy, Energy-Dispersive X-ray Spectroscopy, and Differential Scanning Calorimetry. In vitro dissolution studies revealed that Eudragit®-S100-coated aminated nanomaterials prevented the burst release of the loaded catechin in the acidic environment, with approximately 90% of the catechin only being released at colonic pH (pH > 7) with a supercase II transport mechanism. As a result, silica nanoparticles coated with Eudragit®-S100 would provide an innovative and promising approach in targeted nanomedicine for the oral delivery of catechin and related medicines for treating diseases related to the colon, such as colorectal cancer and irritable bowel syndrome.

Mucoadhesive self-emulsifying delivery systems for ocular administration of econazole.

AIM: Development of mucoadhesive self-emulsifying drug delivery systems (SEDDS) providing a prolonged ocular residence time for poorly soluble active pharmaceutical ingredient. METHODS: l-Cysteine was covalently linked to 6-mercaptonicotinamide. The obtained ligand, Cysteine-6-mercaptonicotinamide (Cys-6-MNA) was attached to Eudragit® L100-55 via a carbodiimide mediated amide bond formation. The resulting entirely S-protected thiolated Eudragit® L100-55 was characterized regarding the degree of modification as well as stability toward oxidation in the presence of strong oxidizing agent (H2O2). The S-protected thiolated Eudragit® L100-55 was incorporated into SEDDS via hydrophobic ion pairing with benzalkonium chloride (BAK) in a concentration of 2% (m/m). S-protected thiolated Eudragit® L100-55-BAK ion pair SEDDS (S-protected thiolated EU-BAK SEDDS) were characterized regarding their physicochemical and mucoadhesive properties. Econazole nitrate (EN) was incorporated into SEDDS in concentration of 1% (m/m) and in vitro drug release was assessed. Furthermore, toxicity study was performed on procine corneas via resazurin assay. RESULTS: The entirely S-protected thiolated Eudragit® L100-55 exhibited 282 ±â€¯78.25 µmol of MNA per gram of polymer. Ellman's test confirmed no free thiol groups and stability study showed no significant increase in dynamic viscosity overtime. The droplet size of developed SEDDS in simulated lacrimal fluid was below 100 nm with polydispersity index below 0.3. S-protected thiolated EU-BAK SEDDS exhibited 2.5-fold higher mucoadhesive properties than blank SEDDS on ocular mucosa. S-protected thiolated EU-BAK SEDDS showed sustained EN release over period of 8 h and no pronounced corneal toxicity in 0.5% (m/v) concentration. CONCLUSION: Accordingly, these mucoadhesive SEDDS can be considered as promising ocular delivery system for EN.