pH响应型蔗渣木质素水凝胶的制备及其对蛋白质的控释性能

该研究以蔗渣木质素和甲基丙烯酸为原料合成了pH敏感型蔗渣木质素/聚甲基丙烯酸水凝胶,对其合成条件、pH敏感性、溶胀-退溶胀性能以及对牛血清蛋白的控释等性质进行研究,并采用红外光谱、扫描电镜等对凝胶进行表征。结果表明:(1)对凝胶溶胀比影响的因素由大到小依次为甲基丙烯酸用量、交联剂用量、催化剂用量、反应的温度、木质素用量。当甲基丙烯酸单体浓度为1.75 mol·L~(-1)、木质素浓度为25 g·L~(-1)、交联剂浓度为3.25×10~(-2)mol·L~(-1)、引发剂浓度为1.25×10~(-2)mol·L~(-1)、反应温度为65℃时,所得水凝胶在模拟肠液中的溶胀比最大(28.16 g·g~(-1))。与不加木质素的聚甲基丙烯酸水凝胶相比,蔗渣木质素/聚甲基丙烯酸水凝胶的溶胀比有所下降,但其敏感pH由4~5碱移至6~8。(2)蔗渣木质素/聚甲基丙烯酸水凝胶的溶胀—退溶胀可逆性受组成的影响较大,但相对于聚甲基丙烯酸水凝胶,蔗渣木质素/聚甲基丙烯酸水凝胶对pH值的敏感响应性更强、响应速率更快,同时能在更短时间内达到溶胀平衡。(3)加入木质素可以提高水凝胶对牛血清蛋白的负载量,所试验的蔗渣木质素/聚甲基丙烯酸水凝胶样品对牛血清蛋白的最大负载量可达577 mg·g~(-1)。(4)牛血清蛋白在12 h后基本可达释放平衡;在模拟胃液中,牛血清蛋白的释放率仅10%,而在模拟肠液中释放率达92%。pH响应型蔗渣木质素/聚甲基丙烯酸水凝胶可以作为口服型蛋白类药物的潜在载体。     

Novel complex hydrogels based on N-carboxyethyl chitosan and quaternized chitosan and their controlled in vitro protein release property

A novel pH-responsive hydrogel (CHC) composed of N-carboxyethyl chitosan (CEC) and N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) was synthesized by the redox polymerization technique. Turbidimetric titrations were used to determine the stoichiometric ratio of these two chitosan derivatives. The hydrogel was characterized by FT-IR, thermal gravimetric analysis (TGA), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). The dynamic transport of water showed that the hydrogel reached equilibrium within 48 h. The swelling ratio of CHC hydrogel depended significantly on the pH of the buffer solution. The performance of the CHC as a matrix for the controlled release of BSA was investigated. It was found that the release behavior was determined by pH value of the medium as well as the intermolecular interaction between BSA and the hydrogels.     

Pectin-coated chitosan microgels crosslinked on superhydrophobic surfaces for 5-fluorouracil encapsulation

5-Fluorouracil (5-FU)-loaded chitosan microgels for oral and topical chemotherapy were prepared applying a superhydrophobic surface-based encapsulation technology. Drug-loaded chitosan dispersions were cross-linked and then coated with drug-free chitosan or pectin layers at the solid-air interface in a highly efficient and environment-friendly way. The size of the microgels (with diameters of ca. 280 and 557 μm for the chitosan seeds and pectin-coated microgels respectively) was the lowest obtained until now using similar biomimetic methodologies. The microgels were characterized regarding 5-FU release profiles in vitro in aqueous media covering the pH range of the gastrointestinal tract, and cytotoxicity against two cancer cell lines sensitive to 5-FU. Owing to their control of 5-FU release in acidic medium, calcium pectinate-coated microgels can be considered as suitable for oral administration. Growth inhibition of cancer cells by 5-FU was greater when incorporated to chitosan microgels; these being potentially useful for treatment of skin and colorectal tumors.     

Design of polymeric microparticles for pH-responsive and time-sustained drug release

We described the design of uniform microencapsulates with almost 100% encapsulation efficiency, synthesized without organic solvents, via microfluidic spray drying of water-based dispersions of pH-responsive methacrylic acid polymers (Eudragit^® L 30D-55). The effects of incorporating water-based network-forming materials in the formulations on pH-responsiveness and controlled release patterns of enteric microparticles were observed. Acid hydrolysed tetraethoxysilane (TEOS) was used to form an interpenetrating, rigid framework of silica, whereas Eudragit^® NE (a copolymer based on ethyl acrylate and methyl methacrylate) was added to produce a more flexible polymeric network. The spray-dried microparticles generally displayed crumbled or buckled morphologies dependent on drying temperatures, due to large hydrodynamic sizes of solutes in feed dispersions. The drug release kinetics of microparticles were sensitive to the type and the added amount of network-forming materials, due to different colloidal interactions between Eudragit^® L and either silica or the copolymer. This study demonstrated a strategy to design enteric microparticles with different microstructural properties and drug release behaviours through understanding of colloidal interactions between constituents of matrix materials.     

Enzymatic synthesis of a 6-sialyl lactose analogue using a pH-responsive water-soluble polymer support

The Letter describes a strategy for the enzymatic synthesis of glycans based on a pH-responsive water-soluble polymer. In neutral condition, the polymer is water-soluble and convenient for in-solution enzymatic synthesis, whereas in acidic condition (pH lower than 4.0), the polymer disconnects with the product and becomes insoluble, which can be easily removed. A 6-Sialyl lactose analogue was synthesized as a model reaction using this approach.     

角蛋白载药纳米颗粒的制备及药物可控释放性能研究*

目的:以角蛋白作为药物载体材料,制备智能响应性药物递送系统,研究其药物装载和释放性能。方法:利用去溶剂法制备角蛋白纳米颗粒(KNP),以罗丹明B(RB)和姜黄素(Cur)为亲水性和疏水性模式药物,制备载药KNP。利用钨灯丝扫描电镜(SEM)、动态光散射(DLS)、傅里叶变换红外光谱(FTIR)和药物体外释放实验等对KNP的尺寸、形貌、结构、载药和释药性能进行研究。结果:成功制备出粒径均一、约为300 nm 的KNP,能够装载亲水性和疏水性药物。载药颗粒在体外释放研究中表现出pH和氧化还原双重响应性。结论:利用去溶剂法,简便、安全地制备了分散性良好且具有pH和氧化还原双重响应性释放特性的角蛋白载药纳米颗粒,为角蛋白作为智能响应型药物递送载体的研究和应用提供了参考。     

Biodegradable and biocompatible polyampholyte microgels derived from chitosan, carboxymethyl cellulose and modified methyl cellulose

Two biocompatible and biodegradable polyampholyte microgels, namely chitosan-carboxymethyl cellulose (CS-CMC) and chitosan-modified methyl cellulose (CS-ModMC) were synthesized by an inverse microemulsion technique. The CS-CMC microgel system was pH-responsive while the CS-ModMC system possessed both pH and thermo-responsive properties. For CS-CMC system, the number of -OCH₂COOH and -NH₂ groups was determined to be 1.5 and 1.1 meq/g of microgel, respectively. In the pH range of 4-9, the zeta potential values varied from +10 to −40 mV, while the hydrodynamic radius varied from 160 nm in the swollen state (acidic and basic pH) to 110 nm in the “collapse” state (neutral pH). Furthermore, TEM micrographs confirmed the swelling/deswelling behaviour of CS-CMC microgel particles at acidic, neutral and basic conditions. For CS-ModMC system, the number of -OCH₂COOH and -NH₂ groups was determined to be 0.8 and 0.6 meq/g microgel, respectively. In the pH range of 4-9, the surface charge on the microgels varied from +25 to −60 mV and the hydrodynamic radii were 190 nm at low pH, 80 nm at neutral pH, to 120 nm at a high pH. In vitro drug release studies confirmed that CS-CMC microgels could encapsulate and release a model drug, thus they could potentially be used as biocompatible and biodegradable drug carriers.     

Design and development of pH-responsive HSPC:C12H25-PAA chimeric liposomes

The application of stimuli-responsive medical practices has emerged, in which pH-sensitive liposomes figure prominently. This study investigates the impact of the incorporation of different amounts of pH-sensitive polymer, C₁₂H₂₅-PAA (poly(acrylic acid) with a hydrophobic end group) in l-α-phosphatidylcholine, hydrogenated (Soy) (HSPC) phospholipidic bilayers, with respect to biomimicry and functionality. PAA is a poly(carboxylic acid) molecule, classified as a pH-sensitive polymer, whose pH-sensitivity is attributed to its regulative –COOH groups, which are protonated under acidic pH (pKa ～4.2). Our concern was to fully characterize, in a biophysical and thermodynamical manner, the mixed nanoassemblies arising from the combination of the two biomaterials. At first, we quantified the physicochemical characteristics and physical stability of the prepared chimeric nanosystems. Then, we studied their thermotropic behavior, through measurement of thermodynamical parameters, using Differential Scanning Calorimetry (DSC). Finally, the loading and release of indomethacin (IND) were evaluated, as well as the physicochemical properties and stability of the nanocarriers incorporating it. As expected, thermodynamical findings are in line with physicochemical results and also explain the loading and release profiles of IND. The novelty of this investigation is the utilization of these pH-sensitive chimeric advanced Drug Delivery nano Systems (aDDnSs) in targeted drug delivery which relies entirely on the biophysics and thermodynamics between such designs and the physiological membranes and environment of living organisms.