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.     

pH敏感性P(AM-AA-co-C8PhEO10Ac)水凝胶溶胀动力学及其对茶碱的控释

以丙烯酰胺(AM)、丙烯酸(AA)和丙烯酸辛基酚聚氧乙烯醚酯(C8PhEO10Ac)为单体,采用自由基交联共聚法合成了具有pH敏感性的P(AM-AA-co-C8PhEO10Ac)水凝胶.研究了pH、单体配比对凝胶溶胀性能、溶胀动力学和退溶胀动力学的影响.初步探讨了模拟胃液(pH=1.4)、肠液(pH=7.4)中水凝胶对茶碱的控释情况.结果表明:凝胶具有高溶胀、退溶胀速率和良好的pH敏感性等特征;水凝胶的扩散行为在pH=7.4的缓冲溶液中为非Fickian扩散模式;载药凝胶在模拟肠液中对药物的累积释放率明显大于胃液中的累积释放率,其中n(C8PhEO10Ac)∶n(AM)∶n(AA)为1∶20∶30的载药水凝胶对茶碱的累积释放率最大.     

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。     

壳聚糖/聚乙二醇/聚丙烯酸复合水凝胶的制备及药物控制释放行为研究

本文以壳聚糖(CS)、聚乙二醇(PEG)和丙烯酸(AA)为原料,制备了复合水凝胶CS/PEG/PAA。研究了负载四种具有不同结构和性质的药物(烟酸、烟酰胺、异烟肼和5-氟尿嘧啶)的复合水凝胶CS/PEG/PAA的药物控制释放行为。结果表明,烟酰胺和异烟肼在pH=1.80的缓冲溶液中的药物累积释放率(R)大于其在pH=6.86的缓冲溶液中的释放率;烟酸却在pH=6.86的缓冲溶液中的药物累积释放率(R)大于其在pH=1.80的缓冲溶液中的释放率。而5-氟尿嘧啶在两种缓冲溶液中的药物累积释放量相当。因此,复合水凝胶CS/PEG/PAA也许可以作为一种新型释放药物的载体。     

氨基功能化介孔二氧化硅对布洛芬的吸附和缓释性能研究

采用后合法对介孔二氧化硅SBA-15进行氨基改性,并以改性后材料NH2-SBA-15为载体,以疏水性药物布洛芬(IBU)为模型药物分子,通过浸渍法把IBU填充到载体的孔道内。利用XRD、低温N2吸附-脱附和FT-IR等测试手段,研究了载体的结构及载体与药物间的相互作用。结果表明,IBU通过扩散和化学吸附作用填充到了载体的孔道内,并且载体表面与IBU间存在较强的化学作用。体外模拟释放实验结果显示,与未改性的SBA-15相比,改性后样品NH2-SBA-15对IBU的释放较慢,体现了明显的药物缓释性能。     

磁性微胶囊的制备及其药物缓控释性能

用乳液-凝胶法制备了磁性壳聚糖/海藻酸钠微胶囊. 在壳聚糖/海藻酸钠微胶囊中掺入Fe3O4磁性中空球, 使微胶囊具有磁靶向性能. 以头孢拉定作为模型药物研究了载药磁性微胶囊的载药量、包封率及药物缓控释性能等. 结果表明, 提高头孢拉定的初始浓度可以提高载药量, 却不利于提高药物的包封率. 所制备的微胶囊在各种缓冲溶液中长时间内具有显著的缓释效果, 并具有pH 刺激响应释放的性能, 即在模拟胃液中的药物释放率大大降低, 而在模拟体液和肠液中的释放时间大大延长, 可达50 h以上. 另外, 在外加磁场作用下, 微胶囊表现出良好的磁定向运动性能, 为磁靶向药物输送提供基础.     

中空介孔硅球原位接枝聚苯胺及其pH响应性药物控制释放行为

通过原位化学氧化聚合的方法,在中空介孔二氧化硅纳米粒子表面成功接枝上了聚苯胺(HMSsPANI).借助透射电镜(TEM)、红外光谱(FTIR)、紫外可见吸收光谱(UV-Vis)、氮气脱附吸附等温测试(BET)、热失重(TGA)、小角粉末衍射(XRD)和zeta电位测试等手段表征了其结构性质.通过循环伏安曲线研究,发现HMSs-PANI分散体系在不同pH条件下具有电化学活性的转变性质,证实了HMSs-PANI在酸性条件下能够进行有效的掺杂从而具有电化学活性.最后用HMSs-PANI来负载抗癌药物盐酸阿霉素(DOX),其展现了良好的酸性pH可控释放行为,在pH=7.4时,22 h后仅有15%的药物累计释放量.在pH=5的条件下,22 h后累计释放量达到44%,而在pH=4条件且同样时间之下,释放量为60%.总之,合成的HMSs-PANI酸响应药物控制释放体系在药物传输领域具有潜在应用.     

酮洛芬/酸改性蒙脱土缓释体系的制备及体外释药研究

以盐酸改性蒙脱土为药物载体,采用离子交换法制备了酮洛芬/酸改性蒙脱土(KPF/acid-MMT)复合物.借助X射线衍射(XRD)、比表面积分析和扫描电子显微镜(SEM)等手段对复合物进行了结构表征;采用透析法研究了介质pH值对KPF/acid-MMT释放性能的影响;运用3种数学模型对其体外释放行为进行拟合.结果表明:经酸改性后,蒙脱土的比表面积由19.66 m~2/g增加到202.84 m~2/g,载药量由18.09%提高到37.24%;在人工模拟胃液(pH=1.2)和人工模拟肠液(pH=6.8)中,酮洛芬的累积释放量分别为18.6%和86.7%;零级动力学模型能更好地拟合和描述KPF/acid-MMT在人工模拟肠液中的体外释放行为.酸改性蒙脱土能有效提高药物的负载量,KPF/acid-MMT可实现药物的定向释放和缓释性能,有望制成肠道缓释口服药物制剂.     

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。     

基于埃洛石的载药凝胶小球的制备及性能研究

采用离子凝胶法制备了一种新的壳聚糖-g-聚丙烯酸/埃洛石/海藻酸钠(CTS-g-PAA/HT/SA)凝胶小球。研究了HT含量对载药凝胶小球的溶胀性、包封效率和释放性能等的影响;同时也讨论了凝胶小球的pH敏感性和双氯芬酸钠(DS)的释放行为。结果表明:HT含量对载药凝胶小球的溶胀率、包封效率和累积释放率有明显的影响,在HT含量为30%时,溶胀率、包封效率和12h累积释放率分别达到32.84%、91.07%和100%;另外,载药凝胶小球具有较好的pH敏感性;在pH=2.1的释放介质中DS几乎不释放,而在pH=6.8的释放介质中缓慢释放;DS释药机理为溶胀控释。     

Synthesis, characterization and sustaining controlled release effect of mesoporous SBA-15/ramipril composite drug

A loading of ramipril in SBA-15 (Santa Barbara Amorphous) mesoporous material was studied. (SBA-15)-ramipril composite material was characterized by chemical analysis, infrared spectroscopy, powder X-ray diffraction, low temperature N₂ adsorption–desorption at 77 K characterization techniques. Ramipril drug release processes from SBA-15 host to simulated body fluid (SBF), simulated gastric juice (SGJ), simulated intestinal fluid (SIF) were monitored in a simulated way and actions of the sustained release of (SBA-15)-ramipril was studied. The results showed that the loading amount of ramipril drug in SBA-15 was 90.30 mg/g. The cumulative sustained release rate of ramipril composite drug in SBF achieved 99.7 % after 27 h. When the sustained release of composite drug in SGJ was 8 h, the maximum cumulative sustained release ratio achieved 54.9 %. When the sustained release of composite drug was 9 h in SIF, the maximum cumulative sustained release ratio achieved 34.9 %. The method described in this study is suitable for carrying ramipril drug on SBA-15, and a new carrier to load ramipril drug was found. Meanwhile, the efficacy of ramipril drug and time efficacy could be improved.     

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.     

pH-Controllable drug release using hydrogel encapsulated mesoporous silica

Amine-functionalized mesoporous SBA-15 silica loaded with bovine serum albumin (BSA) has been successfully encapsulated with a thin layer coating of poly(acrylic acid) PAA, with the entrapped BSA being released from the PAA-encapsulated SBA-15 at the higher pH value of 7.4 rather than at the lower pH value of 1.2. This novel drug delivery system has a potential application in the release of protein drug to the site of higher pH value, such as small intestine or colon.     

Poly(lactic acid)-coated mesoporous silica nanosphere for controlled release of venlafaxine

Two types of mesoporous silica nanospheres (MSNs) were synthesized for use as controlled-release agents. One was prepared by grafting with 5,6-dihydroxyhexylsilane (DH-MSN) and the other one by further coating with cholic acid-crosslinked poly(lactic acid) (CA-PLA-MSN). We studied the release of the antidepressant venlafaxine from each of the materials in simulated gastric fluid (SGF), in simulated gastric acid solution (SGA), and in simulated intestinal fluid without pancreatin (SIF). The CA-PLA-MSN material was able to significantly delay the release of the drug in intestinal condition compared with gastric acid surrounding due to the fast decomposition rate of PLA in gastric acid. Moreover, it successfully avoided the initial burst to a certain extent in SGF. The enzyme pepsin played a favorable obstruct role in both DH-MSN and CA-PLA-MSN systems to reduce release rate. A model based on Weibull model was built to fit the release results, and based on it, the mechanisms about release processes were brought out tentatively.     

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.     

Synthesis and physicochemical characterization of amphiphilic triblock copolymer brush containing pH-sensitive linkage for oral drug delivery

A novel and well-defined pH-sensitive amphiphilic triblock copolymer brush poly(lactide)-b-poly(methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate) (PLA-b-PMAA-b-PPEGMA) and its self-assembled micelles were developed for oral administration of hydrophobic drugs. The copolymer and its precursors were synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and ring-opening polymerization (ROP) techniques. The molecular structures and characteristics were confirmed by GPC, (1)H NMR, and FT-IR. The critical micelle concentration (CMC) values of PLA-b-PMAA-b-PPEGMA in aqueous medium varied from 1.4 to 2.6 mg/L, and the partition equilibrium constant (K(v)) of pyrene in micellar solutions ranged from 2.873 × 10(5) to 3.312 × 10(5). The average sizes of the self-assembled blank and drug-loaded micelles were 140-250 nm determined by DLS in aqueous solution. The morphology of the micelles was found to be spherical by SEM. Nifedipine (NFD), a poorly water-soluble drug, was selected as the model drug and wrapped into the core of micelles via dialysis method. The in vitro release behavior of NFD from the micelles was pH-dependent. In simulated gastric fluid (SGF, pH 1.2), the cumulative release percent of NFD was relative low, while in simulated intestinal fluid (SIF, pH 7.4), more than 96% was released within 24 h. All the results showed that the pH-sensitive PLA-b-PMAA-b-PPEGMA micelle may be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior.     

Modified nanoporous silicas for oral delivery of the water insoluble organotin compound: loading and release of methylphenyltin dichloride as an anti-tumor drug model

Different nanoporous silica materials, MCM-41, MCM-48 and SBA-15, were modified by pyridine and their applications for oral drug delivery system were evaluated. These pyridine functionalized nanoporous silicas were loaded with a water insoluble diorganotin(IV) dichloride complex as an antitumor drug model and its release from them were investigated by changing pH. An efficient pH-responsive carrier system was constructed by coordination of the pyridine group in modified nonoporous materials to tin complex. In vitro, releasing of loaded tin complex was studied in three different kinds of fluids, including a simulated gastric medium and a simulated body fluid. The loading and releasing of the diorganotin(IV) dichloride from various modified nanoporous silicas and also a non-porous silica (SiO₂) were investigated, and the results were compared. In addition, the effect of some factors such as pH, time of loading and releasing were investigated through this study.     

Controlled drug release studies of atenolol using differently sulfonated acryloxyacetophenone and methyl methacrylate copolymer resins as drug carriers

2-Acryloxyacetophenone(AAP) was prepared and subjected to suspension polymerization with methyl methacrylate(MMA) using azobisisobutyronitrile(AIBN) as free radical initiator.The differently sulfonated AAP-MMA cross-linked copolymer cationic exchange resins were prepared by sulfonation with concentrated sulphuric acid at 70 °C.Several characteristics of the prepared resins were evaluated,i.e.FTIR,the ion-exchange capacity(IEC),thermo gravimetric analysis(TGA),particle size distribution and microscopic morphology.The resin characteristics were altered with degree of sulfonation,providing that differently sulfonated resins could be prepared.The behavior of atenolol(ATL) loading and in vitro release in the USP stimulated gastric and intestinal fluids of the obtained resins were evaluated.The drug loaded in the resin increased with increasing degree of sulfonation and hence the drug binding site in resin employed.The drug release was lower from the resins with higher content of sulfonic group due to the increase in the diffusive path depth.The drug release was a little lower in stimulated gastric fluid(SGF) than in stimulated intestinal fluids(SIF).The basic groups,ionized to a little greater extent in SGF and preferred binding with the resin rather than releasing.Hence,the differently sulfonated resins could be utilized as novel carriers for drug delivery.     

Synthesis and characterization of ramose tetralactosyl-lysyl-chitosan-5-fluorouracil and its in vitro release

In order to improve drug loading and achieve a good release effect, this paper adopts the ramose method, choosing chitosan as the carrier and 5-fluorouracil (5-Fu) as a model drug. Ramose chitosan-lysyl-5-Fu(3) and ramose tetralactosyl-lysyl-chitosan-5-Fu(6) were synthesized successfully, then the in vitro release of (6) was researched. The results show that the drug loading of (3) and (6) are 9.17 and 1.63% (w/w), respectively. The in vitro release behavior of (6) in pH 7.4 phosphate buffer solution and pH 1.2 HCl?CKCl solution were studied. The zero order release time that (6) maintains in alkaline and acidic media are 64 and 24?h, and the total release by 184?h are 71.97 and 82.34%, respectively. The performance is smooth throughout the whole stage of release, and the concentration of cumulative release is lower in the alkaline environment than in the acidic environment over the same time.