A novel class of organo- (hydro-) gelators based on ascorbic acid

A library of novel, lipid-modified derivatives of ascorbic acid was shown to exhibit highly attractive properties as surfactants, emulsifiers, oil soluble antioxidants, and highly effective gelators in organic solvents and especially water. In these systems, intermolecular hydrogen bonding and van der Waals forces act synergistically to induce gelation as confirmed by spectroscopic studies. The morphology of the formed gel has been characterized by scanning electron microscopy.     

The controlled release of a drug from biodegradable chitosan gel beads

Chitosan (CS) forms a gel in solutions with a pH above 12, and the gelation occurs at pH of about 9 in 10% amino acid solutions. In this paper, we investigated the enzymatic degradation and the drug release profile of this novel CS gel beads. The degradability of the CS gel beads was affected by the CS properties, e.g. the degree of deacetylation. The release of prednisolone (PS), as a model drug, from the CS gel beads was sustained significantly compared with the gel prepared with NaOH only. However, the release was not able to be sustained by the increment of NaOH concentration in the solution employed for the preparation of CS gel beads. We also investigated the control of drug release from CS gel beads by application of a complex formed between chondroitin sulfate (Cho) and CS. The release of PS from the CS gel beads treated with Cho was prolonged, and the release pattern was not affected by the treatment time. The time to 50% drug release was about 5 min with PS powder, about 200 min in CS gel beads with 10% glycine (Gly) (pH 9.0), and about 330 min in the CS gel beads with 10% Gly (pH 9.0) treated with Cho. Thus CS gel beads appear promising as a vehicle for sustained drug delivery, and the degradation of CS gel beads may be controlled by the degree of deacetylation of CS.     

Novel Gel with Controllable Strength for In-Depth Conformance Control: Bulk Gelation Performance and Propagation Properties in Porous Media

Polymer gel has been widely used to control excessive water production in mature oilfields. However, in view of reservoir conditions characterized by serious heterogeneous thick oil layers, high strength and in-depth propagation are required of polymer gel to achieve good treatment efficiency. Based on the concept of in-depth conformance control, a novel gel with controllable strength composed of polymer, resorcinol/hexamethylenetetramine (HMTA), acetic acid and gel strength modifier was developed. The effects of component concentrations on bulk gelation properties were investigated. The microstructures of conventional gel and novel gel at different aging time were studied by scanning electron microscopy (SEM), which can provide insight into the mechanism of controllable gel strength. Moreover, sandpack flow experiments were carried out on sandpacks (Φ2.5 × 100 cm) with multi-point pressure taps to investigate whether the novel gel can propagate in porous media. Compared with the conventional gel, SEM results showed that the three-dimensional network structure of novel gel was weakened more seriously, resulting in the decrease of gel strength. Due to decreased gel strength at different aging time, the novel gel can propagate in porous media to achieve in-depth conformance control.     

Effects of acidic catalysts on the microstructure and biological property of sol–gel bioactive glass microspheres

Sol–gel bioactive glasses have been developed for bone tissue regeneration and drug delivery systems as they have the unique mesoporous structure and high bioactivity in vitro. To develop more reliable drug delivery and bone tissue repair systems, it is necessary to control the morphology and microstructure of bioactive glasses. For this purpose, bioactive glass microspheres (BGMs) were prepared by a sol–gel co-template technology using acids as catalysts. We studied the effects of different acids (citric acid, lactic acid and acetic acid) on the microstructure and apatite-forming bioactivity of BGM. The apatite-forming bioactivity was carried out in simulated body fluid (SBF). The microstructure and apatite-forming bioactivity of BGMs were characterized by various methods. Results showed that acetic acid had little effect on the structure and bioactivity of BGMs. Differently, the morphology and microstructure of BGMs could be controlled by changing citric acid and lactic acid concentrations. In vitro bioactivity test indicated that citric acid and lactic acid derived BGMs possessed the better apatite-forming capacity than that derived by acetic acid.     

Influence of processing parameters on regeneration kinetics and morphology of porous cellulose from cellulose–NaOH–water solutions

The kinetics of cellulose regeneration in acetic acid bath from cellulose–8% NaOH–water solutions and gels is studied as a function of gelation conditions, acid concentration and bath temperature. The diffusion coefficient of NaOH from cellulose solution or gel into regenerating bath was calculated. It does not depend either on gelation mode or on acid concentration. On the contrary, cellulose regeneration from non-gelled solutions is slower than from a gel. The increase in bath temperature induces diffusion coefficient increase obeying Arrhenius law. Scanning electron microscopy images of regenerated swollen-in-water freeze-dried cellulose and of the same samples dried in supercritical CO₂ show highly porous morphology. CEMEF is a Member of the European Polysaccharide Network of Excellence (EPNOE), .     

Characteristics and antioxidant activity of catechin-loaded calcium pectinate gel beads prepared by internal gelation

Catechin-loaded calcium pectinate gel beads prepared by internal gelation were characterized for their catechin entrapment efficiency and release behavior. The entrapment efficiency was higher when the beads were prepared with a lower catechin-to-pectin ratio, shorter gelling time, higher pectin concentration, and lower acetic acid concentration. The entrapment efficiency was much higher under all tested conditions, when the beads were prepared by internal gelation instead of external gelation. The catechin release was slower for the beads prepared with lower catechin-to-pectin ratio, longer gelling time, and higher concentrations of pectin and acetic acid in both simulated gastric and intestinal fluids. Antioxidant power of catechin was effectively maintained in alkaline simulated intestinal fluid when catechin was entrapped within the beads, compared to cases where it was not entrapped, indicating that the beads can protect catechin molecules from the alkaline environment and release them in a sustained fashion.     

Preparation and drug retention of biodegradable chitosan gel beads.

Chitosan (CS) gel beads containing drug could be prepared in amino acid solutions of pH about 9, despite the requirement for a pH above 12 for gelation in water. This phenomenon was observed not only in amino acid solutions but also in solutions of compounds having amino groups. A solute concentration of more than 10% was required for preparation of gel beads at pH 9. Gelation of the CS beads required about 25 to 40 min, depending on the species of amino acid. Lidocaine hydrochloride (LC) as a model drug was retained in the beads to about 20 to 35% of the theoretical total amount, despite being a water-soluble drug. The release of LC from the CS gel beads was prolonged. The release pattern was not affected by the species of amino acid or CS, or the preparation time.     

Chitosan nanoparticles: a promising system in novel drug delivery

The ability of nanoparticles to manipulate the molecules and their structures has revolutionized the conventional drug delivery system. The chitosan nanoparticles, because of their biodegradability, biocompatibility, better stability, low toxicity, simple and mild preparation methods, offer a valuable tool to novel drug delivery systems in the present scenario. Besides ionotropic gelation method, other methods such as microemulsion method, emulsification solvent diffusion method, polyelectrolyte complex method, emulsification cross-linking method, complex coacervation method and solvent evaporation method are also in use. The chitosan nanoparticles have also been reported to have key applications in parentral drug delivery, per-oral administration of drugs, in non-viral gene delivery, in vaccine delivery, in ocular drug delivery, in electrodeposition, in brain targeting drug delivery, in stability improvement, in mucosal drug delivery in controlled drug delivery of drugs, in tissue engineering and in the effective delivery of insulin. The present review describes origin and properties of chitosan and its nanoparticles along with the different methods of its preparation and the various areas of novel drug delivery where it has got its application.     

Relationship between physicochemical characteristics and functional properties of chitosan

In order to select an ideal chitosan (CS) species as a material for implantation vehicle to control drug release in the body, the relationship between physicochemical characteristics (including molecular weight, degree of deacetylation, and viscosity) and functional properties (including ability to form spherical gel, control of drug release from CS gel, and biodegradation of CS) was investigated for various CS. The ease of spherical gel formation in aqueous amino acid solution or aqueous solution containing metal ions was affected mainly by viscosity of the CS solution. Drug diffusion rate from the CS gel was controlled by density of the gel matrix structure, which was governed by viscosity of the CS solution prior to gelation. Biodegradation of CS tended to vary with degree of deacetylation. However, linear relationships for these trends were not observed, and the possibility that characteristics other than CS molecular weight, degree of deacetylation, and viscosity of the CS solution, such as distribution of acetamide groups in the CS molecule affect functional properties of CS, was also indicated. These observations demonstrate that CS functions are affected by various CS characteristics and that investigation of individual CS characteristics is important for the selection of the appropriate CS as a material for drug delivery vehicles.     

Nasal in situ gel containing hydroxy propyl ��-cyclodextrin inclusion complex of artemether: development and in vitro evaluation

The objective of the present investigation was to explore the formulation and evaluation of in situ gel for the nasal delivery of artemether (ARM), a poorly water-soluble antimalarial agent using temperature induced gelation technique using Pluronic with mucoadhesive polymer Hydroxy Propyl Methyl Cellulose (HPMC) K4M in different ratios. Initially, due to low water solubility, an inclusion complex of the antimalarial artemether (ARM) in hydroxypropyl-??-cyclodextrin (HP??CD) was prepared and characterized. The in situ gels so prepared were characterized for its gelation properties, viscosity, gel strength, mucoadhesion, drug content, drug release rate and for its histopathological studies. Pluronic and HPMC based in situ gel (PLH2) showed the effective gelation, viscosity, gel strength and drug release properties along with good mucoadhesive strength, it is further subjected for stability studies carried out at 30 ± 2 °C and 60 ± 5% RH for 90 days in order to know the influence of temperature and relative humidity on drug content and on drug release profile. Histological examination of formulations did not show any remarkable damage to nasal mucosa. The formulation also retained the good stability at accelerated conditions over the period of 90 days. Owing to these properties it can be used as an effective delivery system for the nasal route. These in situ gelling systems would be definitely useful for cerebral malaria.     

Milk proteins as vehicles for bioactives

Milk proteins are natural vehicles for bioactives. Many of their structural and physicochemical properties facilitate their functionality in delivery systems. These properties include binding of ions and small molecules, excellent surface and self-assembly properties; superb gelation properties; pH-responsive gel swelling behavior, useful for programmable release; interactions with other macromolecules to form complexes and conjugates with synergistic combinations of properties; various shielding capabilities, essential for protecting sensitive payload; biocompatibility and biodegradability, enabling to control the bioaccessibility of the bioactive, and promote its bioavailability.The review highlights the main achievements reported in the last 3 years: harnessing the casein micelle, a natural nanovehicle of nutrients, for delivering hydrophobic bioactives; discovering unique nanotubes based on enzymatic hydrolysis of α-la; introduction of novel encapsulation techniques based on cold-set gelation for delivering heat-sensitive bioactives including probiotics; developments and use of Maillard reaction based conjugates of milk proteins and polysaccharides for encapsulating bioactives; introduction of β-lg–pectin nanocomplexes for delivery of hydrophobic nutraceuticals in clear acid beverages; development of core-shell nanoparticles made of heat-aggregated β-lg, nanocoated by beet-pectin, for bioactive delivery; synergizing the surface properties of whey proteins with stabilization properties of polysaccharides in advanced W/O/W and O/W/O double emulsions; application of milk proteins for drug targeting, including lactoferrin or bovine serum albumin conjugated nanoparticles for effective in vivo drug delivery across the blood-brain barrier; beta casein nanoparticles for targeting gastric cancer; fatty acid-coated bovine serum albumin nanoparticles for intestinal delivery, and Maillard conjugates of casein and resistant starch for colon targeting.Major future challenges are spot-lighted.     

Cyclodextrin based novel drug delivery systems

The versatile pharmaceutical material cyclodextrin’s (CDs) are classified into hydrophilic, hydrophobic, and ionic derivatives. By the early 1950s the basic physicochemical characteristics of cyclodextrins had been discovered, since than their use is a practical and economical way to improve the physicochemical and pharmaceutical properties such as solubility, stability, and bioavailability of administered drug molecules. These CDs can serve as multi-functional drug carriers, through the formation of inclusion complex or the form of CD/drug conjugate and, thereby potentially serving as novel drug carriers. This contribution outlines applications and comparative benefits of use of cyclodextrins (CDs) and their derivatives in the design of novel delivery systems like liposomes, microspheres, microcapsules, nanoparticles, cyclodextrin grafted cellulosic fabric, hydrogels, nanosponges, beads, nanogels/nanoassemblies and cyclodextrin-containing polymers. The article also focuses on the ability of CDs to enhance the drug absorption across biological barriers, the ability to control the rate and time profiles of drug release, drug safety, drug stability, and the ability to deliver a drug to targeted site. The article highlight’s on needs, limitations and advantages of CD based delivery systems. CDs, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes.     

Synthesis and Gelation Behavior of Cholesteryl Glycinate Anthraquinone‐2‐Carboxylamide and Cholesteryl Glycinate 9,10‐Dimethyloxyl Anthracene‐2‐Carboxylamide

Cholesteryl glycinate anthraquinone‐2‐carboxylamide (CGAC), an electron acceptor, and cholesteryl glycinate 9,10‐dimethyloxyl anthracene‐2‐carboxylamide (CGDAC), an electron donor, were synthesized and characterized via ¹H NMR, IR and elemental analysis. Gelation studies demonstrated that acetic acid and some mixed solvents containing more than 30% acetic acid could be efficiently gelled by CGAC. Unlike CGAC, CGDAC could not gel any of the solvents tested. SEM and AFM studies showed that the gelator in the gel system of CGAC‐acetic acid self‐assembled into a fiber‐like tubular structure, and the tubules were further self‐tangled into networks. Introduction of CGDAC into the CGAC‐acetic acid system had little effect upon the gel properties of the CGAC‐acetic acid system. This observation was explained by considering interruption of the possible donor‐acceptor interaction between CGAC and CGDAC due to protonation of the latter. Comparing the structure and gelation properties of CGAC with those of similar structures reported in the literature further indicates that a small change in the structure of the linker between the A (aromatic) part and S (steroidal) part of the ALS type gelators affects the gelation behaviors of the ALS type gelators significantly.     

麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

Spontaneous formation of gel emulsions in organic solvents and commercial fuels induced by a novel class of amino acid derivatized surfactants

A novel class of amphiphiles, sodium N-(n-dodecyl-2-aminoethanoyl)-l-amino acidate, have been synthesized. These amphiphiles have been shown to form oil-in-water-type gel emulsions with a high internal-phase ratio in organic solvents as well as in commercial fuels simply by agitation. No heating and cooling cycle was required for the formation of gels. The amphiphiles also showed efficient phase-selective gelation in the presence of excess water. The minimum gelator concentrations for the amphiphiles in the solvents employed have been determined. The effects of the chain length of the hydrocarbon tail and the chirality of a representative amphiphile on its ability to promote gelation in a given organic solvent have been investigated. Also, the effect of acid and alkali on the gelation has been examined. The optical microscopic picture of the gel emulsion showed foamlike structures with oil compartments separated by the continuous aqueous phase. The mechanism of the formation of gel emulsions has been discussed.     

In situ organically cross‐linked polymer gel for high‐temperature reservoir conformance control: A review

Polymer gel has been established as water‐blocking agents in oil recovery application. In this practice, a mixture known as gelant is injected into target area and set into a semisolid gel after a certain adequate time. Besides profile modification and water shutoff, the role of the polymer gel in conformance control is to block high permeability regions, before diverting injected water from high permeability to low permeability zones of the reservoir. It is to boost the oil displacement and sweep efficiency. This is the key to improve oil recovery in the heterogeneous oil reservoirs. However, very limited gels are applicable for harsh conditions, especially in high‐temperature reservoirs. Organically cross‐linked polymer is 1 of the materials for conformance control at high‐temperature reservoirs. Many experimental works and field applications have exhibited the potential of this technology. This paper presents a concise review on this polymer gel for conformance control at high‐temperature wells. Firstly, in situ organically cross‐linked polymer gel has been introduced, and the reason of the use over other types of polymer gels is summarized. The early studies of organically cross‐linked gel systems are also discussed, followed by the chemistry and the gelation mechanisms. An extensive review on factors that affect gelation kinetics and field applications is also discussed in some detail.     

乙酰化对壳聚糖-明胶海绵结构和性能的影响

用乙酸酐对壳聚糖与明胶共混物进行乙酰化,然后冷冻干燥制备乙酰化壳聚糖-明胶海绵,并研究乙酰化对海绵结构与性能的影响。用盐酸环丙沙星作模型药物,探讨载药海绵的抑菌效果。结果表明:制得的海绵具有多孔结构,随壳聚糖在混合物中含量的增加,海绵的吸水率和保水率先增后减;随着乙酰化程度的提高,海绵的吸水率先减后增,而保水率与吸水率的变化规律相反。酶对海绵的降解率不受壳聚糖和明胶混合比例的影响,但随海绵乙酰化程度的增加而增加。载药海绵的抑菌效果与海绵中壳聚糖含量有关。     

Radiation preparation and diffusion behavior of thermally reversible hydrogels

Temperature sensitive PolyNIPAAm hydrogels in the form of rod were prepared from the binary system of NIPAAm/water and ternary system of NIPAAm/Bis/water by γ-irradiation with ⁶⁰Co source at room temperature, respectively. The prepared hydrogels had obvious temperature sensitivity (LCST is about 35.0 °C) and suitable mechanical properties. The incorporation of cross-linking agent, N, N′-methylene-bisacrylamide (Bis), into the binary system of monomer/water reduced the gelation dose. The maximum swelling ratio of hydrogels was decreased with the increasing of dose or the incorporation of Bis. The diffusion behavior of water in hydrogels obtained in this work was investigated. In addition, the drug delivery of fluoro uracili (Fu-5) from the hydrogels was investigated.     

Hydrogel-shelled biodegradable microspheres for sustained release of encapsulants

Biodegradable microparticles are promising for the sustained release of encapsulated lipophilic drugs. In particular, the microparticles with uniform size show excellent linearity of cumulated release over time with minimized initial burst. Here, we encapsulate the biodegradable microparticles with a hydrogel shell to improve the controllability over the sustained release and suspension stability. With a capillary microfluidic device, monodisperse oil-in-water-in-oil (O/W/O) double-emulsion droplets are produced to have a toluene solution of polylactic acid (PLA) in the core and sodium alginate and calcium-ethylenediaminetetraacetic acid (EDTA) complex in the shell, whereas the continuous oil phase contains acetic acid. As the toluene evaporates, PLA consolidates to form a microsphere in the core. At the same time, acetic acid diffuses from the continuous phase to the water layer, which causes the dissociation of the Ca-EDTA complex and the gelation of alginate. The hydrogel-shelled PLA microspheres are transferred from the oil to an aqueous solution of calcium chloride, which further tightens the gel shell. The resulting core-shell microspheres show sustained release of encapsulants for extended periods as the hydrogel shell serves as a diffusion barrier. Moreover, the hydrogel shells prevent interparticle agglomeration and adhesion to the solid walls, securing high suspension stability during the injection.     

基于豆甾醇衍生物的超分子凝胶的合成与性能

设计合成出两种含有不同结构单元的新型豆甾醇衍生物凝胶因子（化合物1和2）。通过扫描电子显微镜（SEM）、傅里叶变换红外光谱（FT-IR）和紫外-可见光谱（UV-Vis）等技术手段对形成凝胶的结构和性能进行研究。结果表明,两种凝胶因子可分别在二甲基亚砜及甲醇溶剂中形成稳定的凝胶。其中化合物1还可在二甲基亚砜/水混合溶液体积比分别为9∶1、8∶2和7∶3中形成稳定的凝胶。当化合物1和2在DMSO溶剂中以质量浓度均为12 mg/mL形成凝胶时,二者的凝胶-溶胶相转变温度（T_gel）分别为51和46 ℃,表明随着凝胶因子中甾体结构单元的增加,其形成凝胶的热稳定性显著下降。在此基础上,以化合物1制备的凝胶为载体,通过紫外-可见光谱对罗丹明B、亚甲基蓝和阿霉素的包封与释放应用进行了研究。结果表明,制备的凝胶可以作为药物载体,并在240 min时在水中达到的最大释放值为84％。本文为豆甾醇衍生物凝胶的制备,及将其作为药物载体在药物输送领域的应用提供了有益的思路。