pH-sensitive self-assembling property of poly(ethyleneimine)/cinnamic acid mixture and its effect on pH-dependent release of monoolein cubic phase

Poly(ethyleneimine) (PEI)/cinnamic acid (CA) mixture was self-assembled into microsphere in aqueous phase. As the pH value increased, the self-assembly became hardly formed. As the molar ratio of the amino group of PEI to the carboxyl group of CA increased, the pH window for the formation of self-assembly became broader. The phase transition temperature of cubic phase was 58.5–67.5°C, depending on the PEI/CA content. The release of dye loaded in cubic phase containing PEI/CA increased in a first-order fashion. The release degree was higher at a lower pH value.     

Novel strategy for encapsulation and targeted delivery of poorly water-soluble active substances

Carriers for targeted delivery and controlled release of poorly water-soluble active substances (PWSAS) are facing three challenges: (a) the encapsulation issues, (b) limitations of PWSAS water solubility, and (c) burst drug release which can be pharmacologically dangerous and economically inefficient. The present study brings a novel strategy for encapsulation and controlled release of PWSAS—caffeine in concentrations which are higher than its maximal water solubility without the possibility of burst effect. The modification of hydrophilic carrier based on poly(methacylic acid) was done using casein and liposomes. To further increase the maximal caffeine loading inside the carrier nicotinamide was used. The release study of the encapsulated PWSAS was elaborated with respect to morphology of the carriers and interactions that could be established between its structural components. The carriers swelling and the release of caffeine and nicotinamide were also investigated depending on caffeine concentration, the presence of different liposomal formulations and the volume ratio of liposomal formulation, in three media with different pH simulating the path of the carrier through the human gastrointestinal tract. The synthesized carriers are promising candidates for encapsulation of PWSAS in concentrations which are higher than its maximal water solubility and for the targeted delivery of those dosages.     

Temperature- and pH-sensitive membrane formed from blends of poly(vinylidene fluoride)-graft-poly(N-isopropylacrylamide) and poly(acrylic acid) microgels

Temperature- and pH-responsive membranes prepared from blends of poly(vinylidene fluoride)-graft-poly(N-isopropylacrylamide)(PVDF-g-PNIPAM) copolymer and poly(acrylic acid) (PAA) microgels in N,N-dimethylformamide (DMF) solution by phase inversion method. PAA microgels help PNIPAM chains largely enrich onto membrane surface. Furthermore, adding PAA microgels increases the porous size, porosity and hydrophilic property of the blend membrane. The membranes show temperature-sensitivity between 30 and 35 °C, and pH-sensitivity between pH 3 and 5 on permeating aqueous solutions. Meanwhile, the blend membranes keep good antifouling property even if one of the hydrophilic components becoming hydrophobic in response to temperature or pH stimuli, which is superior to single-sensitive PVDF membrane.     

Radiation Synthesis of pH-Sensitive Hydrogels From Carboxymethyl Cellulose/Poly(ethylene Oxide) Blends as Drug Delivery Systems

Gamma irradiation was used to prepare hydrogels from carboxymethyl cellulose (CMC) and poly(ethylene oxide) (PEO) blends in the form of films. The hydrogels were characterized by IR spectroscopy, differential scanning calorimetry, thermogravimetric analysis, mechanical testing, and scanning electron microscopy. The swelling in different buffers of different pH values was also studied. The results indicated the formation of network structure and that the swelling of hydrogels is thermo- and pH-sensitive. The CMC/PEO hydrogels were evaluated for the possible use in drug delivery field, in which the release profile of ketoprofen, as a drug model was investigated.     

Heteroarm Star-Shaped Poly (N-isopropylacryamide-co-itaconic acid) Copolymer Prepared by Glucose Core as ATRP Initiator

Star-shaped temperature- and pH-sensitive poly (N-isopropylacryamide-co-itaconic acid) copolymer is synthesized by atom transfer radical polymerization (ATRP) using 1,2,3,4,6-penta-O-Isobutyrylbromide-α-D-glucose as 5-Arm ATRP Initiator. For ATRP of itaconic acid (IA), carboxylic groups of IA are protected via silylation by hexamethyldisilazane (HMDS) using Fe₃O₄ as a magnetic catalyst. The polymerization is carried out in 2-propanol/toluene 50:50 (v/v) mixed solvent at 90°C. Structure of copolymers is studied with FT-IR, ¹H NMR, glass transition temperature (Tg), and scanning electron microscopy (SEM). Results of temperature, pH, and percentage variation on polymer structure and the effects on lower critical solution temperature (LCST), which is investigated with potentiometery and conductometry, show that LCST of copolymer is around body temperature and demonstrate the ability of this polymer in the design of controlled drug delivery systems. According to the obtained results from naltrexone release, the investigated star-shaped copolymer may have potential applications in the controlled release of drugs.     

Reactive and stimuli-responsive maleic anhydride containing macromers – multi-functional cross-linkers and building blocks for hydrogel fabrication

Macromers with functional groups that allow for chemical derivatization, polymerization reactions or impart specific physico-chemical properties are functional building blocks for polymeric systems used in different biomedical applications. With this motivation, a series of oligomeric macromers was synthesized by free radical polymerization of maleic anhydride (MA) with N-isopropylacrylamide (NiPAAm) and pentaerythritol diacrylate monostearate (PEDAS). This chemical design provides anhydride groups for effective reactivity of the macromers with amines and other nucleophiles, copolymerized NiPAAm for temperature responsiveness and lipophilic stearate domains for increased hydrogel stability. Macromers were synthesized with different MA co-monomer feeds and oligomeric molecules (Mn below 5000 Da) were obtained with MA contents between 7% and 27% as determined by titration. The fraction of chemically intact anhydrides was calculated to range from 75% to 80%. The ability of the macromers to cross-link di- or oligovalent amines as a function of MA content was investigated rheologically. It was also demonstrated that monovalent amines, e.g. aminofluorescein, could be grafted to the macromer chain utilizing only a fraction of the anhydride functionalities. The derivatized macromers could still participate in cross-linking reactions due to the remaining anhydrides. Temperature sensitivity was shown for aqueous solutions of macromers with fully dissociated anhydride groups. The solutions were additionally responsive to changes in calcium ion concentration and pH. Extracts from macromer cross-linked polyether hydrogels showed no toxicity on L929 fibroblasts.The macromers have perspective as biocompatible cross-linkers for hydrogel fabrication from various biomacromolecules with the opportunity to decorate the gels with monoamine molecules that alter the biological or physico-chemical properties.     

Acetals moiety contained pH-sensitive amphiphilic copolymer self-assembly used for drug carrier

pH-sensitive nanoparticles were prepared from a novel amphiphilic copolymer poly(2-phenyl-1, 3-dioxan-5-yl methacrylate-co-2-hydroxyethyl acrylate), poly(PDM-co-HEA), which was synthesized from the pH-sensitive hydrophobic monomer 2-phenyl-1, 3-dioxan-5-yl methacrylate (PDM) and the hydrophilic monomer 2-hydroxyethyl acrylate (HEA) with unit ratio (4:6) via radical polymerization. The random amphiphilic polymer could form nanoparticles in aqueous media with sizes of about 167 nm (PDI = 0.03). The morphology of the nanoparticles was determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). When the nanoparticles solution was adjusted to pH = 5.5, sizes of the nanoparticles increased from 167 nm to about 800 nm within 24 h, characterized by DLS. The critical aggregation concentration (CAC) of the copolymer was determined to be 5.3 mg/L (1.7 × 10⁻⁷ M). The insoluble Nile Red could be delivered into the Hep3B cells by the nanoparticles and released in cytoplasm determined by fluorescence microscopy.     

pH响应性聚合物修饰的空心介孔硅球的制备

将有机硅RAFT试剂三甲氧基硅基丙基三硫代羰基苄基酯（BTPT）固载于硅球表面,通过可逆加成-断裂链转移自由基聚合表面接枝法制备了pH值、温度双敏感聚合物聚甲基丙烯酸-2-（二甲氨基）乙酯（PDMAEMA）修饰的纳米硅球,通过表面保护法在常温下用氨水对该修饰过的硅球进行刻蚀,制得PDMAEMA修饰的纳米空心介孔硅球（HMS@PDMAEMA）。通过核磁、红外、GPC和透射电子显微镜等方法对其结构和表面形貌进行了表征,并用纳米粒度及zeta电位仪测试了其pH值响应行为,预测HMS@PDMAEMA在癌症药物的控制释放和基因递送等领域具有潜在的应用价值。     

Synthesis and properties of degradable hydrogels of konjac glucomannan grafted acrylic acid for colon-specific drug delivery

In this paper, we reported the synthesis and properties of novel hydrogel systems designed for colon targeted drug delivery. The gels were composed of konjac glucomannan (KGM), copolymerized with acrylic acid (AA) and cross-linked by N,N-methylene-bis-(acrylamide) (MBAAm). The influence of various parameters on the equilibrium swelling ratios of the hydrogels was investigated. The swelling ratio was inversely proportional to the content of MBAAm. It was possible to modulate the degree of swelling of the gels by changing cross-linking density of the polymer. The gels' swelling ratio has sensitive respondence to the environmental pH value variation. The results of degradation test show that the hydrogels retain the enzymatic degradation character of KGM and they can be degraded for 52.5% in 5 days by Cellulase E0240. In vitro release of model drug 5-aminosalicylic acid (5-ASA) was studied in the presence of Cellulase E0240 in pH 7.4 phosphate buffer at 37 °C. The accumulative release percent of 5-ASA reached 95.19% after 36 h and the drug release was controlled by the swelling and degradation of the hydrogels.