Investigation of in vitro permeability and in vivo pharmacokinetic behavior of bare and functionalized MCM-41 and MCM-48 mesoporous silica nanoparticles: a burst and controlled drug release system for raloxifene

In the present work, MCM-41 and MCM-48 type of nanoparticles were successfully engineered. Effect of nanosize and amine functionalization on drug release, in vitro intestinal absorption and in vivo pharmacokinetic behavior was investigated in a comprehensive manner. The tailor-made bare and surface decorated MCM-41 and MCM-48 were synthesized and evaluated for their mesoporous skeleton, pore size, particle size, surface area, zeta potential, etc. by nitrogen sorption, DLS, TEM, etc. Incorporation of raloxifene (RLF) was affirmed using optimized immersion-solvent evaporation technique and its success confirmed by DSC, IR, and XRD analysis. TGA analysis revealed higher %grafting of amine groups on the exterior and larger RLF encapsulation into mesoporous derivate. The detailed in vitro release study revealed SGF to be the most compatible media for RLF showing an initial burst release from pristine nanoparticles and a delayed release from surface coated nanoparticles. Furthermore, release kinetics model data demonstrated Weibull and Higuchi as the best fit models for bare and amine-functionalized nanoparticles respectively. Moreover, an in vitro permeability study on Caco-2 cell line revealed higher absorption by engineered nanoparticle as compared to pure RLF and its marketed formulation. The supremacy in the in vivo pharmacokinetic parameters of RLF-41 and RLF-48 was demonstrated with 3.33 and 3.50 times enhancement in the bioavailability of RLF with respect to RLF suspension. To sum up, the results obtained were superior and promising for synthesized nanoparticles and more precisely for MCM-48 amongst them.     

Functionalization of mesoporous MCM-41 for the delivery of curcumin as an anti-inflammatory therapy

In this study, mesoporous silica nanoparticles (MSNs) composed of MCM-41 were synthesized and modified with amine groups (i.e., NH₂) to form NH_2/MCM-41, which was loaded with curcumin (CUR) to form CUR@NH₂/MCM-41 to create an efficient carriers in drug delivery systems (DDSs). The three samples (i.e., pure MCM-41, NH₂/MCM-41, and CUR@NH₂/MCM-41) were characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transition electron microscopy (TEM), and a thermogravimetric analyzer (TGA). The study investigated the effect of the carrier dose, CUR concentration, pH, and contact time on the drug loading efficiency (DLE%) by adsorption. The best DLE% for MCM-41 and NH₂/MCM-41 was found to be 15.78 and 80%, respectively. This data demonstrated that the Langmuir isotherm had a greater correlation coefficient (R²) of 0.9840 for MCM-41 and 0.9666 for NH₂/MCM-41 than the Freundlich and Temkin isotherm models. A pseudo-second-order kinetic model seems to fit well with R² = 0.9741 for MCM-41 and R² = 0.9977 for NH₂/MCM-41. A phosphate buffer solution (PBS) with a pH of 7.4 was utilized to study CUR release behavior. As a result, the full release after 72 h was found to have a maximum of 74.1% and 29.95% for pure MCM-41 and NH₂/MCM-41, respectively. The first-order, Weibull, Hixson-Crowell, Korsmeyer-Peppas, and Higuchi kinetic release models were applied to releasing CUR from CUR@MCM-41 and CUR@NH₂/MCM-41. The Weibull kinetic model fit well, with R² = 0.944 and 0.96912 for pure MCM-41 and NH₂/MCM-41, respectively.     

氟化MCM-41的制备及超声触发释药性能研究

采用微波法制备了MCM-41,并将其与NH4F反应制得氟化MCM-41(F-MCM-41),采用浸渍法将抗肿瘤药物5-氟尿嘧啶(5-FU)分别组装到MCM-41和氟化MCM-41中。采用XRD、FT-IR、低温N2吸附和TG对MCM-41、氟化MCM-41和药物组装体进行了表征,考察了常规条件和超声条件下组装体在人工模拟胃液中的药物释放行为。结果表明,药物组装体超声条件下的药物释放速率明显优于常规释放。     

氢氯噻嗪／MCM-41载药体系的制备与缓释作用研究

用微波辐射法合成介孔分子筛MCM-41，采用浸渍法将利尿药物氢氯噻嗪组装到介孔分子筛MCM-41孔道中，用XRD、低温N2吸附、IR对MCM-41及药物组装体进行了表征；研究了组装体的载药量、载药时间、在体外人工胃液中的释放等。结果显示合成的分子筛MCM-41具有规则的孔径结构，比表面积为1211m^2/g；分子筛MCM-41作为药物的载体具有较短的载药时间（t=26h），较大的载药量48％（m（药物）/优（载体）），较低的释放速率，表明制得了氢氯噻嗪／MCM-41缓释释放体系。     

Development and evaluation of hollow mesoporous silica microspheres bearing on enhanced oral delivery of curcumin

The aim of this work is to develop curcumin-loaded hollow mesoporous silica microspheres (HMSMs@curcumin) to improve the poor oral bioavailability of curcumin. Hollow mesoporous silica microspheres (HMSMs) were synthesized in facile route using a hard template. HMSMs and HMSMs@curcumin were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption measurements, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). In addition, to demonstrate the potential application of the HMSMs@curcumin, cytotoxicity, in vitro release behavior and in vivo pharmacokinetics of curcumin loaded in these HMSMs were investigated by using of Caco-2 cells and Sprague-Dawley (SD) rats, respectively. These mono-dispersed HMSMs exhibited high drug loading ratio and encapsulation efficiency due to the mesoporous shell and hollow core. The excellent characteristics of HMSMs such as mono-dispersed morphology, smooth surface, uniform, ordered and size-narrowing mesopores resulted in a good in vitro release profile of curcumin from HMSMs@curcumin. Moreover, an impressive improvement in the oral absorption of curcumin and prolonged systemic circulation time were achieved in the in vivo animal studies. In addition, the good biocompatibility of developed HMSMs with Caco-2 cells was confirmed based on the in vitro cytotoxicity assay. In conclusion, this system demonstrated a great potential for efficient delivery of curcumin in vitro and in vivo, suggesting a good prospect for its application in clinic for therapeutic drug delivery in future.     

Characterization of platinum–iron catalysts supported on MCM-41 synthesized with rice husk silica and their performance for phenol hydroxylation

Mesoporous material RH-MCM-41 was synthesized with rice husk silica by a hydrothermal method. It was used as a support for bimetallic platinum−iron catalysts Pt–Fe/RH-MCM-41 for phenol hydroxylation. The catalysts were prepared by co-impregnation with Pt and Fe at amounts of 0.5 and 5.0 wt.%, respectively. The RH-MCM-41 structure in the catalysts was studied with x-ray diffraction, and their surface areas were determined by nitrogen adsorption. The oxidation number of Fe supported on RH-MCM-41 was + 3, as determined by x-ray absorption near edge structure (XANES) analysis. Transmission electron microscopy (TEM) images of all the catalysts displayed well-ordered structures, and metal nanoparticles were observed in some catalysts. All the catalysts were active for phenol hydroxylation using H₂O₂ as the oxidant at phenol : H₂O₂ mole ratios of 2 : 1, 2 : 2, 2 : 3 and 2 : 4. The first three ratios produced only catechol and hydroquinone, whereas the 2 : 4 ratio also produced benzoquinone. The 2 : 3 ratio gave the highest phenol conversion of 47% at 70 °C. The catalyst prepared by co-impregnation with Pt and Fe was more active than that prepared using a physical mixture of Pt/RH-MCM-41 and Fe/RH-MCM-41.     

Formulation and optimization of spray-dried amlodipine solid dispersion for enhanced oral absorption

Objective: To enhance the oral absorption of photosensitive amlodipine free base, which exhibits a slow dissolution rate and low permeability characteristics, an amorphous solid dispersion system was formulated and characterized.

Material and methods: The solid dispersion was prepared by dispersing the amlodipine free base in excess dextrin (1:10 by weight) using a spray-drying technique in the presence of a minimum amount (0.9% w/w) of SLS as an absorption enhancer. The dextrin-based solid dispersion of amlodipine (Amlo-SD) was evaluated in term of formulation, characterization and in vivo absorption study, as well as the spray-drying process was also optimized.

Results and discussion: The Amlo-SD particles were spherical with a smooth surface and an average particle size of 12.9 μm. Amlodipine was dispersed in an amorphous state and its content remained uniform in the Amlo-SD. The physicochemical stability of the Amlo-SD was maintained at room temperature for 6 months and the photostability was considerably improved. The dissolution of the Amlo-SD was much faster than that of amlodipine at pH 1.2 and 6.8. Amlo-SD produced significantly higher plasma concentrations of amlodipine in rats than amlodipine alone. Amlo-SD with and without SLS provided 2.8- and 2.0-fold increase in AUC, respectively: the difference seems to be attributed to a permeability enhancement effect by SLS.

Conclusion: The Amlo-SD with SLS system is a potential formulation option for amlodipine.