Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

Review of electrospun hydrogel nanofiber system: Synthesis,Properties and Applications

Hydrogel-based nanofibers or vice versa are a relatively new class of nanomaterials, in which hydrogels are structured in nanofibrous form. Structure and size of the material directly governs its functionality, therefore, in hydrogel science, the nanofibrous form of hydrogels enables its usage in targeted applications. Hydrogel nanofiber system combines the desirable properties of both hydrogel and nanofiber like flexibility, soft consistency, elasticity, and biocompatibility due to high water content, large surface area to volume ratio, low density, small pore size and interconnected pores, high stiffness, tensile strength, and surface functionality. Swelling behavior is a critical property of hydrogels that is significantly increased in hydrogel nanofibers due to their small size. Electrospinning is the most popular method to fabricate “hydrogel nanofibers,” while other processes like self-assembly, solution blowing and template synthesis also exist. Merging the characteristics of both hydrogels and nanofibers in one system allows applications in drug delivery, tissue engineering, actuation, wound dressing, photoluminescence, light-addressable potentiometric sensor (LAPS), waterproof breathable membranes, and enzymatic immobilization. Treatment of wastewater, detection, and adsorption of metal ions are also emerging applications. In this review paper, we intend to summarize in detail about electrospun “hydrogel nanofiber” in relation to its synthesis, properties, and applications.     

Designing Semipermeable Hydrogel Shells with Controlled Thickness through Internal Osmosis in Triple-Emulsion Droplets

Hydrogel shells that compartmentalize the water core from the aqueous surrounding provide molecular selectivity on size and charge in transmembrane transport. It is highly demanding to produce thin hydrogel shells to minimize diffusion length and maximize core volume. Here, internal osmosis in water-in-oil-in-water-in-oil (W/O/W/O) triple-emulsion droplets is used to produce thin hydrogel shells enclosing a large water core. The triple-emulsion droplets are prepared to have an ultrathin middle oil layer using a capillary microfluidic device. The innermost water droplet has a higher osmolarity than the outer water layer containing photopolymerizable hydrogel precursors, which pumps water from the outer layer to the core through the ultrathin oil layer by the osmosis. Therefore, the outer layer gets thinner and hydrogel precursors are enriched while the size of the triple-emulsion droplets remains unchanged. Through photopolymerization of precursors and phase transfer from oil to water, hydrogel shells enclosing water core are produced in the water environment; the oil layer is ruptured for molecular exchange through the shells. The thickness and composition of the hydrogel shells are precisely controllable by the osmotic conditions. The shells show a high permeation rate due to the thinness as well as controlled cut-off threshold of permeation for neutral and charged molecules.     

Long-term sustained-released in situ gels of a water-insoluble drug amphotericin B for mycotic arthritis intra-articular administration: preparation,in vitro and in vivo evaluation

Amphotericin B (AMB) was often used in intra-articular injection administration for fungal arthritis, because it could often bring a satisfactory therapeutic efficacy and a minimum systemic toxic side effect. However, because of the multiple operations and the frequent injections, the compliance of the patients was bad. Therefore, to develop a long-term sustained-released preparation of AMB for mycotic arthritis intra-articular administration is of great significance. The purpose of present study was to develop a long-term sustained-released in situ gel of a water-insoluble drug AMB for mycotic arthritis intra-articular administration. Based on the evaluations of the in vitro properties of the formulations, the formulation containing 10% (w/w) ethanol, 15% (w/w) PG, 0.75% (w/w) HA, 5% (w/w) purified soybean oil, 0.03% (w/w) α-tocopherol, 15% (w/w) water and 55% (w/w) glyceryl monooleate was selected as a suitable intra-articular injectable in situ gel drug delivery system for water-insoluble drug AMB. Furthermore, the results of the in vivo study on rabbits showed that the selected formulation was a safe and effective long-term sustained-released intra-articular injectable AMB preparation. Therefore, the presented in situ AMB gel could reduce the frequency of the administration in the AMB treatment of fungal arthritis, and then would get a good patient compliance.     

Formulation of sage essential oil (Salvia officinalis,L.) monoterpenes into chitosan hydrogels and permeation study with GC-MS analysis

This study deals with the formulation of natural drugs into hydrogels. For the first time, compounds from the sage essential oil were formulated into chitosan hydrogels. A sample preparation procedure for hydrophobic volatile analytes present in a hydrophilic water matrix along with an analytical method based on the gas chromatography coupled with the mass spectrometry (GC-MS) was developed and applied for the evaluation of the identity and quantity of essential oil components in the hydrogels and saline samples. The experimental results revealed that the chitosan hydrogels are suitable for the formulation of sage essential oil. The monoterpene release can be effectively controlled by both chitosan and caffeine concentration in the hydrogels. Permeation experiment, based on a hydrogel with the optimized composition [3.5% (w/w) sage essential oil, 2.0% (w/w) caffeine, 2.5% (w/w) chitosan and 0.1% (w/w) Tween-80] in donor compartment, saline solution in acceptor compartment, and semi-permeable cellophane membrane, demonstrated the useful permeation selectivity. Here, (according to lipophilicity) an enhanced permeation of the bicyclic monoterpenes with antiflogistic and antiseptic properties (eucalyptol, camphor and borneol) and, at the same time, suppressed permeation of toxic thujone (not exceeding its permitted applicable concentration) was observed. These properties highlight the pharmaceutical importance of the developed chitosan hydrogel formulating sage essential oil in the dermal applications.     

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.     

温度敏感葡聚糖凝胶的合成及其细胞相容性研究

合成了N-异丙基丙烯酰胺（NIPAAm）与葡聚糖的共聚水凝胶，利用红外光谱表征了单体和凝胶结构，研究了水凝胶在去离子水和细胞培养基中的温度响应性，并对凝胶进行了细胞培养和脱附研究．结果表明，共聚凝胶具有很好的温度敏感性和细胞相容性，可以通过控制温度变化，实现对细胞的无损伤脱附．     

Investigation of the relationships between the chain organization and rheological properties of atactic poly(vinyl alcohol) hydrogels

The structure and rheological behavior of atactic poly(vinyl alcohol) (a-PVA) hydrogels prepared by freeze/thaw cycles were investigated as a function of polymer concentration and number of freeze/thaw cycles. The presence of phases with different mobilities was observed using ¹³C CP/MAS and DP/MAS NMR experiments. The degree of crystallinity of the a-PVA-rich phase was determined by ¹H NMR free decay experiments. Measurements of the shear storage and loss modulus were performed at a fixed frequency of 1 Hz and a strain value of 0.1%, i.e. under conditions where the deformation imposed on the gel structure is entirely reversible. Results thus obtained showed that an increase in the number of freeze/thaw cycles induces an increase in the degree of crystallinity in the polymer-rich phase together with an increase in the storage modulus. The a-PVA hydrogels became more fragile as the number of freeze/thaw cycles was increased. Moreover, both the percentage of protons in a rigid environment measured by ¹H NMR and the storage modulus values tended to a limiting value after six freeze/thaw cycles. These results show that the first five or six freeze/thaw cycles play a very important role in determining the hydrogel structure and rheological properties. A more detailed comparison of NMR and rheological data led to the conclusion that the storage modulus is mainly controlled by the a-PVA crystallinity while the hydrogen bond interactions have a much smaller contribution.