Synthesis and characterization of mesoporous SBA-15/propranolol hydrochloride for controlled drug release study

Propranolol hydrochloride was incorporated into SBA-15 mesoporous material host by impregnation method to obtain host-guest nanocomposite material (SBA-15)-propranolol hydrochloride. By spectrophotometry, the amount of propranolol hydrochloride assembly was determined to be 382.05?mg/g (drug/SBA-15). Powder X-ray diffraction test results indicated that during the process of incorporation the framework of the molecular sieve was not destroyed and the molecular sieve still remained its structure ordering. Fourier transform infrared spectra showed that the framework of the prepared host-guest material was remained in good condition. Low-temperature nitrogen adsorption-desorption at 77?K results showed that the surface area and the pore volume of (SBA-15)-propranolol hydrochloride host-guest material decreased compared to those of the host molecular sieve, indicating that propranolol hydrochloride guest molecules have partially occupied the channels of the molecular sieve. Transmission electron microscopy and scanning electron microscopy results indicated that two-dimensional hexagonal mesoporous pore channels of the molecular sieve were retained and (SBA-15)-propranolol hydrochloride composite material remained fibrous crystals and the average diameter of sample was 336?nm. It was discovered in drug release principle in the simulated body fluid that the effective release time of the drug reached 30?h and the maximum cumulative released amount of propranolol hydrochloride was 99.3?%. When drug release time arrived at 5?h in the simulated gastric juice, the maximum cumulative released amount was 51.2?%.When drug release time arrived at 9?h in the simulated intestinal fluid, the maximum cumulative released amount was 70.1?%. The drug sustained release results showed that SBA-15 is a well-controlled drug release carrier.     

基于HPMCP包覆介孔SBA-15的pH敏感药物缓释系统

以肠溶性包衣材料羟丙甲纤维素邻苯二甲酸酯(HPMCP)为原料,在负载法莫替丁(Famo)的SBA-15药片表面包覆聚合物膜,成功制备了一种新型的pH敏感药物缓释系统, 并考察了此缓释系统在不同pH释放环境中的释放行为. 结果表明: 在模拟胃液中(SGF, pH=1.2),HPMCP能致密包覆在药片表面,从而明显延缓Famo的释放速度;而在模拟肠液中(SIF, pH=7.5),HPMCP能够迅速溶于缓释溶液中,因而对Famo释放速度的影响甚微. 因此,可以将这种新型智能药物缓释系统应用于肠道靶向给药.     

5-氟尿嘧啶在pH敏感型分子筛控释载体中的缓释行为

以肠溶性的羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)作为包覆材料,制备了HPMCP包覆的SBA-15介孔分子筛药物控释载体(HPMCP/SBA-15),并考察了抗癌药物5-氟尿嘧啶(5-Fu)负载于控释载体后,在不同pH释放环境中的释放行为.结果表明,在模拟胃液中(pH=1.2),HPMCP能明显地延缓5-Fu的释放速度;药物释放4h后,其释放率仅为15%.而在模拟肠液中(pH=7.5)HPMCP迅速溶解,对5-Fu释放速度的影响甚微;药物释放4h后,释放率可达到80%.与此同时,包覆膜的干燥温度影响5-Fu的释放行为,干燥温度越高,药物在模拟胃液中的释放速度越慢.     

Controlled drug release from bifunctionalized mesoporous silica

Serial of trimethylsilyl-carboxyl bifunctionalized SBA-15 (TMS/COOH/SBA-15) have been studied as carriers for controlled release of drug famotidine (Famo). To load Famo with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized by one-pot synthesis under the assistance of KCl. The mesostructure of carboxyl functionalized SBA-15 (COOH/SBA-15) could still be kept even though the content of carboxyl groups was up to 57.2%. Increasing carboxyl content could effectively enhance the loading capacity of Famo. Compared with pure SBA-15, into which Famo could be hardly adsorbed, the largest drug loading capacity of COOH/SBA-15 could achieve 396.9 mg/g. The release of Famo from mesoporous silica was studied in simulated intestine fluid (SIF, pH=7.4). For COOH/SBA-15, the release rate of Famo decreased with narrowing pore size. After grafting TMS groups on the surface of COOH/SBA-15 with hexamethyldisilazane, the release of Famo was greatly delayed with the increasing content of TMS groups.     

Effects of Morphology and Structural Characteristics of Ordered SBA-15 Mesoporous Silica on Release of Ibuprofen

Three kinds of highly ordered SBA-15 mesoporous materials with different pore sizes and morphologies denoted as LPS-SBA-15 (stick-like with pore size 7.28 nm), CPS-SBA-15 (stick-like with pore size 5.96 nm) and T-SBA-15 (tablet-like with pore size 4.64 nm) have been prepared, characterized and employed as carrier materials. The release behaviors of the ibuprofen in a simulated body fluid from these mesoporous silica materials were studied. The influences of pore size and exterior morphologies of mesoporous silica on the release behaviors of ibuprofen have been investigated. It has been found that the release becomes fast with increasing of pore size and slow with extending of transport pathway, and that the release rate of ibuprofen from the three kinds of SBA-15 is LPS-SBA-15 > T-SBA-15 > CPS-SBA-15. The results show that the inner structure as well as the exterior morphologies of SBA-15 mesoporous silica can seriously affect the release behaviors of ibuprofen.     

pH值响应性毒死蜱/铜席夫碱配合物改性SBA-15的制备及缓释性能

以3-氨丙基三乙氧基硅烷（APTES）、水杨醛和铜离子为改性剂,通过后嫁接法制得铜席夫碱配合物改性SBA-15（Cu-SBA-15）,并以毒死蜱为模型药物,制备了毒死蜱/铜席夫碱配合物改性SBA-15缓释体系。利用TEM、SEM、XRD、N₂吸附-脱附、TG、FTIR和XPS对SBA-15、氨基改性SBA-15（NH₂-SBA-15）、水杨醛希夫碱改性SBA-15（SA-SBA-15）的形貌、结构和Cu-SBA-15的配位情况进行了表征,考察了SBA-15在改性前后对毒死蜱的吸附量和缓释性能,并着重探究了毒死蜱/铜席夫碱配合物改性SBA-15载药体系在不同pH值下的释药行为。结果表明,APTES和水杨醛能够通过后嫁接法修饰于SBA-15,修饰后仍保持十分有序的孔道结构。SBA-15通过改性后,其对毒死蜱的吸附量由100 mg·g^-1增加至195 mg·g^-1,且其对药物的缓释性能也得到改善。毒死蜱/铜席夫碱配合物改性SBA-15缓释体系显示出明显的pH值响应性,pH=3时的释药速率大于pH=11时,而在中性条件下的缓释效果相对最好。载药体系的释药行为可用Riger-Peppas动力学模型来描述,其药物释放由Fick扩散控制。     

pH值响应性毒死蜱/铜席夫碱配合物改性SBA-15的制备及缓释性能

以3-氨丙基三乙氧基硅烷(APTES)、水杨醛和铜离子为改性剂,通过后嫁接法制得铜席夫碱配合物改性SBA-15(Cu-SBA-15),并以毒死蜱为模型药物,制备了毒死蜱/铜席夫碱配合物改性SBA-15缓释体系。利用TEM、SEM、XRD、N2吸附-脱附、TG、FTIR和XPS对SBA-15、氨基改性SBA-15(NH_2-SBA-15)、水杨醛希夫碱改性SBA-15(SA-SBA-15)的形貌、结构和Cu-SBA-15的配位情况进行了表征,考察了SBA-15在改性前后对毒死蜱的吸附量和缓释性能,并着重探究了毒死蜱/铜席夫碱配合物改性SBA-15载药体系在不同pH值下的释药行为。结果表明,APTES和水杨醛能够通过后嫁接法修饰于SBA-15,修饰后仍保持十分有序的孔道结构。SBA-15通过改性后,其对毒死蜱的吸附量由100 mg·g~(-1)增加至195 mg·g~(-1),且其对药物的缓释性能也得到改善。毒死蜱/铜席夫碱配合物改性SBA-15缓释体系显示出明显的pH值响应性,pH=3时的释药速率大于pH=11时,而在中性条件下的缓释效果相对最好。载药体系的释药行为可用Riger-Peppas动力学模型来描述,其药物释放由Fick扩散控制。     

Drug Release Properties of a Series of Adenine‐Based Metal–Organic Frameworks

The drug uptake and release properties of a series of biomolecule‐based metal–organic frameworks (bMOF‐1, bMOF‐4, bMOF‐100, and bMOF‐102) have been studied. The bMOFs were loaded with the small molecule etilefrine hydrochloride and release profiles were collected in both Nanopure water and simulated body fluid (SBF). Each bMOF exhibited an initial burst of drug release at the initial stages of the experiment followed by a gradual release of the remaining drug molecules over time. bMOF‐1 released 50 % of the drug after 15 days and complete release at 80 days in SBF. bMOF‐4 released 50 % of the drug within two days and complete release at 49 days in SBF. bMOF‐100 and bMOF‐102 released 50 % of the drug after 4 h and complete release at 69 and 54 days in SBF, respectively.     

Lymphatic targeting of hematoporphyrin monomethyl ether using poly (butyl-cyanoacrylate) based nanoparticle drug delivery system

The traditional treatment has inevitable drawbacks of nonspecific lymph targeting, poor therapeutic efficiency and residual metastatic for advanced cancer patients with lymph node metastases. To overcome these shortcomings, we prepare a nano-carrier drug delivery system. Photosensitizer hematoporphyrin monomethyl ether (HMME)-loaded poly (n-butylcyanoacrylate) nanoparticles (PBCA-NPs) was prepared successfully. The particle size was approximately 160 nm, the envelopment rate was 87.9%, and the drug loading rate was about 13.4%. The drug release study in vitro showed that the cumulative release rates of HMME-PBCA-NPs group was much less than free HMME group. The drug distribution in different tissues showed that the peak-reach time was 3 h in free HMME group and 6 h in nanoparticles group. All of these results confirmed the slow release characteristic of nanoparticles. In lymph node tissues, the HMME concentrations in HMME-PBCA-NPs group were much higher than those of the free HMME group at any time points we tested, in which the maximum difference concentration of HMME appeared at 6 h (1.2884?±?0.04695 vs. 0.0438?±?0.00558 µg/mg) after drug delivery. The mesenteric lymph nodes of rabbits were enlarged obviously in the NP group than in free HMME group at 6 h after drug delivery. All of these results confirmed the slow release characteristic and the lymphatic targeting characteristic of nanoparticles. In summary, we developed a lymphatic targeting nanoparticles drug delivery system successfully, which showed perfect lymph targeting and has the potential to be a new therapy strategy for advanced cancer patients with lymph node metastasis.     

Dynamic Release of Riboflavin from Ethyl Cellulose Coated Barium Alginate Beads for Gastrointestinal Drug Delivery: An in vitro Study

The present work describes the dynamic release of model drug riboflavin form uncoated and ethyl cellulose coated barium alginate beads in the media of continuous varying pH at the physiological temperature 37°C. The drug release behavior has been studied in the simulating gastric fluid (SGF, pH 1.2) for 0–2 h and then in the simulating intestinal fluid (SIF pH 6.8) for 2–48 h. In addition to the traditional dissolution test (TDT, the dynamic release has also been studied by a newly developed method, called ‘flow through diffusion cell’ (FTDC). The release profiles, obtained by using these two methods have been found to differ appreciably from each other. Moreover, the nature of the solid mass surrounding the beads in the FTDC method also influences the release behavior of beads. The uncoated beads demonstrated faster drug release of drug in the medium of lower pH (i.e., 1.2) as compared to that in the medium of pH 6.8 and the release process was found to be diffusion controlled.     

Submicron particles of SBA-15 modified with MgO as carriers for controlled drug delivery

Submicron particles with modified surface were synthesized by a simple one-pot synthesis approach and used as drug carrier for controlled release. Due to the alkalinity of MgO species on the surface, the amount of a model drug, ibuprofen, adsorbed on the modified surface was increased as compared to pure silica SBA-15 although the surface area was decreased by the surface modification. FTIR investigation indicated that the adsorption state of ibuprofen on MgO modified SBA-15 was different from that on pure silica SBA-15 and pure crystal ibuprofen. The result obtained from in vitro release test exhibited that the surface modification greatly decreased the ibuprofen release rate. In first 6 h in vitro release test, only 63% of the adsorbed ibuprofen was released from the MgO/SBA-15 (Si/Mg=20). In contrast, the release of ibuprofen was complete in 1 h from the pure silica SBA-15 under the same release conditions. The surface modified with MgO created affinity with acidic ibuprofen molecules and retarded the release rate from the mesoporous matrix. In addition, the release rate of ibuprofen could be modulated by varying the content of MgO, and was found to decrease with increasing amount of MgO on surface of SBA-15 submicron particles.     

Preparation and evaluation of nano-hydroxyapatite/poly(styrene-divinylbenzene) porous microsphere for aspirin carrier

A novel vehicle for the delivery of aspirin (ASA) was prepared from porous nano-hydroxyapatite/poly(styrene-divinylbenzene) [nano-HAP/P(St-DVB)] composite microspheres by grafting nano-HAP [Ca10(PO4)6(OH)2] onto porous P(St-DVB) microspheres. Four types of porous composite microspheres were prepared, each with different nano-HAP contents. The ASA-loaded composite microspheres prepared with 10% and 15% nano-HAP (mass ratio) exhibited excellent buoyancy with relatively short instantaneous floating time (within 10 min) and a long sustained floating time (12 h) in simulated gastric juice. They also offered good sustained release of ASA (up to 8 h). Furthermore, these composite microspheres displayed good buffering capacity that prevented the buildup of acidity caused by hydrolysis of ASA, keeping the pH of gastric juice within the normal range (pH 0.9 to 1.5). The results showed that porous nano-HAP/P(St-DVB) composite microspheres prepared with 10% and 15% nano-HAP could be used as a novel drug carrier for ASA, providing a sustained release dose without leading to stomach irritation, a side effect that is often associated with ASA medication.     

Luminescence functionalization of SBA-15 by YVO4:Eu3+ as a novel drug delivery system

Luminescence functionalization of the ordered mesoporous SBA-15 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process, resulting in the formation of the YVO4:Eu3+@SBA-15 composite material. This material, which combines the mesoporous structure of SBA-15 and the strong red luminescence property of YVO4:Eu3+, can be used as a novel functional drug delivery system. The structure, morphology, porosity, and optical properties of the materials were well characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, N2 adsorption, and photoluminescence spectra. As expected, the pore volume, surface area, and pore size of SBA-15 decrease in sequence after deposition of the YVO4:Eu3+ layer and the adsorption of ibuprofen (IBU, drug). The IBU-loaded YVO4:Eu3+@SBA-15 system still shows the red emission of Eu3+ (617 nm, 5D0-7F2) under UV irradiation and the controlled drug release property. Additionally, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU in the system, making the extent of drug release easily identifiable, trackable, and monitorable by the change of luminescence. The system has great potential in the drug delivery and disease therapy fields.     

Metallic nickel supported on mesoporous silica as catalyst for hydrodeoxygenation: effect of pore size and structure

Catalytic hydrodeoxygenation (HDO) of anisole, a methoxy-rich lignin-derived bio-oil model compound, was carried out over a series of Ni-containing (5, 10, 20, and 30 wt%) catalysts with commercial silica and ordered mesoporous silica SBA-15 as support. Both supports and catalysts were characterized by N₂ adsorption–desorption isotherms, X-ray diffraction, CO chemisorption, and transmission electron microscopy (TEM). Catalytic reaction was performed at 250 °C and 10 bar H₂ pressure. Depending on the catalyst support used and the content of active metal, the catalytic activity and product distribution changed drastically. Increase of the nickel loading resulted in increased anisole conversion and C₆ hydrocarbon (benzene and cyclohexane) yield. However, loading more Ni than 20 wt% resulted in a decrease of both conversion and C₆ yield due to agglomeration of Ni particles. In addition, Ni/SBA-15 samples exhibited much stronger catalytic activity and selectivity toward C₆ hydrocarbon products compared with Ni/silica catalysts. The differences in catalytic activity among these catalysts can be attributed to the effect of the pore size and pore structure of mesoporous SBA-15. SBA-15 can accommodate more Ni species inside channels than conventional silica due to its high pore volume with uniform pore structure, leading to high HDO catalytic activity.     

Nanostructured CoMoO4 Supported on Mesoporous SBA-15 for Catalytic Oxidative Dehydrogenation of Propane to Propene

Nanostructured cobalt molybdate catalysts supported on mesoporous silica SBA-15 with different loadings were prepared by citric acid coordination-impregnation method and characterized by XRD, TEM, and BET techniques. The characterization results showed that high loading of well-dispersed crystalline CoMoO₄ may be achieved using citric acid coordination-impregnation method and the mesoporous structure of the support remained intact. The catalytic activity of these catalysts in the oxidative dehydrogenation of propane was investigated. The catalysts of nanostructured cobalt molybdate supported on mesoporous silica SBA-15 showed better catalytic performance than the corresponding bulk composite oxide and nanostructured CoMoO₄ supported on SBA-15 with loading of 13% (mass fraction, w) displayed propene yield of 16.8% at 823 K.     

Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release

MCM-41 and SBA-15 silica materials with spherical morphology and different particle sizes were synthesized and modified by post-synthesis method with 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, were carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N₂ physisorption, thermal analysis, elemental analysis and FT-IR spectroscopy. Surface modification with amino groups resulted in high degree of ibuprofen loading and slow rate of release for MCM-41, whereas it was the opposite for SBA-15. The adsorbed drug content and the delivery rate can be predetermined by the choice of mesoporous material with the appropriate structural characteristics and surface functionality.     

Performances of NaCS–WSC protein drug microcapsules with different degree of substitution of NaCS using sodium polyphosphate as cross-linking agent

Sodium cellulose sulfate–water soluble chitosan (NaCS–WSC) microcapsules loaded with lactoferrin were fabricated with special performances using different degree of substitution (DS) of NaCS and WSC as potential micro-drug-carriers for colon. Effect of using cross-linking agent (sodium polyphosphate) and DS of NaCS on the structures and performances of microcapsules was studied. The results of laser scanning confocal microscope showed that fluorescein isothiocyanate-labeled lactoferrin distributed evenly in the drug-loaded microcapsules with cross-linker. NaCSs (DS: 0.51 and DS: 0.66, respectively) were chosen to prepare lactoferrin loaded microcapsules with WSC and cross-linker for comparison studies. DS of NaCS had some effects on erosion properties in which the erosion ratios of microcapsules with DS of 0.51 were higher than that with DS of 0.66, but showed no effect on swelling behaviors. Drug loading and encapsulation efficiencies of microcapsules (DS: 0.66) were 51.05 ± 0.97 and 75.88 ± 1.44 %, respectively, which were higher than that of microcapsules with DS of 0.51. In vitro release studies showed that the percentage of drug release of microcapsules (DS: 0.51) were higher than that of microcapsules with DS of 0.66 in simulated colonic fluid (pH 6.4) under mechanism of Anomalous (non-Fickian) transport, indicating that they are promising candidates as sustained protein drug delivery carriers with special performances.     

Co-delivery of docetaxel and doxorubicin using biodegradable PEG-PLA micelles for treatment of breast cancer with synergistic anti-tumour effects

Poly(ethylene glycol)-poly(lactic acid) copolymer, prepared by ring opening polymerization, was used as a single platform to co-deliver both hydrophilic doxorubicin and hydrophobic docetaxel (DTX) in a simulated physiological environment. The average size of the negatively charged drug loaded polymeric micelles were found to be 293 nm. The drug loading (%) and encapsulation efficiency (%) were calculated to be 1.21 and 59.0, respectively. The in vitro cytotoxicity test using MCF7 breast cancer cells was conducted using 1 × 10⁴ cells in 10% FBS and 1% antibiotic, and the absorbance of formazan was evaluated at 570 nm. Cell growth inhibition by MTT assay showed viability of 33% of the MCF7 cells after treatment with drug-loaded micelles for 48 h. Controlled release of drugs from the polymeric micelles indicated a burst release effect initially; whereas, 98% of drug could be released at pH 7.4 within a time period of 96 h. Time period for drug release shorten to 48 h only in simulated mild acidic pH (5.4) condition. The in vitro drug release study from micelles indicated synergistic cytotoxicity effect in human metastatic breast cancer MCF7 cell.     

Sodium alginate/HPMC/liquid paraffin emulsified (o/w) gel beads,by factorial design approach; and in vitro analysis

The present study involved development of a novel sodium alginate (SA)/HPMC/light liquid paraffin emulsified (o/w) gel beads containing Diclofenac sodium (DS) as an active pharmaceutical ingredient and its site specific delivery by using hard gelatin capsule fabricated by enteric coated Eudragit L-100 polymer. Emulsified gel beads were formulated by 3-level factorial design, ionic gelatin method. The obtained beads were characterized by Fourier transform infrared, X-ray diffraction and Field emission scanning electron microscope analysis. The variables such as SA (X₁), HPMC (X₂), were optimized for drug loading and in vitro drug release with the help of response surface methodology (RSM). The RSM analysis predicted that SA was significant for both drug loading (p = 0.0005) and drug release (p = 0.0041). HPMC was only significant for drug release (p = 0.0154). The cross-product contribution (2FI) and quadratic model were found to be adequate and statistically accurate with correlation value (R²) of 0.9054 and 0.9450 to predict the drug loading and drug release respectively. An increase in concentration of HPMC and SA decreases the drug loading as well as the drug release. The obtained optimum values of drug loading and DS released were 7.43 % and 85.54 % respectively, which were well in agreement with the predicted value by RSM.     

In-situ synthesis,characterization and antimicrobial activity of viscose fiber loaded with silver nanoparticles

In order to broaden applications of viscose fiber, graft copolymerization of acrylic acid was conducted on its surface followed by in situ loading of Ag nanoparticles (Ag-NPs). The loading amount of Ag-NPs was affected by the concentrations of Ag⁺ and trisodium citrate, and their optimum concentrations were found to be 0.014 and 0.030 g/ml. The Ag-NP-loaded fibers presented a prolonged Ag release behavior in aqueous solution, of which the cumulative release was less than 5 % within 48 h. In addition, the viscose fibers showed good antimicrobial activity against S. aureus, and their consecutive antimicrobial activity was kept at more than 90 % after several washing cycles. Modified viscose fibers, therefore, offer a great opportunity for use as antimicrobial fabrics.