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Potential customers of utilizing Biocatalysis for the Functionality as well as Customization of Polymers.
Furthermore, we demonstrated that CLD-hFGF2 enhances fibroblast migration, and significantly improves skin regeneration for accelerating wound healing without any significant toxicity. This paper highlights the importance of CLD as an emerging delivery system; it is also providing a new and applicable therapeutic research direction through enhancing the skin permeation of hFGF2 to accelerate wound healing.Nanogels were prepared in aqueous media without the use of any organic solvent via a simple polyelectrolyte complexation method between aminated pullulan and fucoidan followed by covalent crosslinking with genipin. Homogeneously distributed genipin crosslinked nanogels (G-PECs) were obtained with a mean hydrodynamic diameter of ~155 nm and zeta potential of 0.86 ± 4.35 mV. Their capacity to bind to human activated platelets was evaluated in vitro, as well as their cytocompatibility within human endothelial cells after 1 day of incubation up to 1000 µg/mL of G-PECs (94.56 ± 7.82% of viable cells). Additional hemolysis tests support the biocompatible character of the developed nanosystems (hemolysis rate of 2.09 ± 0.06% for 1000 µg/mL of G-PECs). Under acid conditions, the surface charge of G-PECs was tuned to around ~10 mV allowing miRNA incorporation via electrostatic interactions. G-PECs were able to promote miRNA delivery inside cells, as demonstrated by fluorescence microscopy images of labelled miRNA. With further studies to demonstrate the biological activity of delivered miRNA, these nanogels could be an interesting platform for miRNA-based therapeutics in atherothrombotic-related diseases thanks to the possibility to target over-expressed P-selectin.Siderophores are low-molecular-weight chelators produced by microorganisms to scavenge iron from the environment and deliver it to cells via specific receptors. Tremendous researches on the molecular basis of siderophore regulation, synthesis, secretion, and uptake have inspired their diverse applications in the medical field. Replacing iron with radionuclides in siderophores, such as the most prominent Ga-68 for positron emission tomography (PET), carves out ways for targeted imaging of infectious diseases and cancers. Additionally, the high affinity of siderophores for metal ions or microorganisms makes them a potent detecting moiety in sensors that can be used for diagnosis. As for therapeutics, the notable Trojan horse-inspired siderophore-antibiotic conjugates demonstrate enhanced toxicity against multi-drug resistant (MDR) pathogens. Besides, siderophores can tackle iron overload diseases and, when combined with moieties such as hydrogels and nanoparticles, a wide spectrum of iron-induced diseases and even cancers. In this review, we briefly outline the related mechanisms, before summarizing the siderophore-based applications in imaging, sensors, and therapeutics.Benznidazole (BZ) and nifurtimox are first-line drugs for the treatment of Chagas disease, with BZ preferred due to its moderate side effects compared to nifurtimox. However, BZ has low aqueous solubility and a low dissolution rate which potentially limit its oral bioavailability. We now report for the first time efforts to improve the aqueous dissolution of BZ via processing and γ-cyclodextrin (γ-CD) complexation using supercritical carbon dioxide (scCO2). We first investigated the solubility of BZ in scCO2 and the effect of scCO2 processing on the solid-state, particle size characteristics and dissolution behaviour of processed BZ compared to un-processed BZ. find more Moreover, the efficacy of scCO2 in dissolving and complexing BZ with γ-CD was studied and compared with conventional freeze-drying (FD). The solubility of BZ in scCO2 was time-dependent (1.78 × 10-6 to 3.18 × 10-5 mol. mol-1) and reached the equilibrium after 10 h. Complexation efficiency and loading capacity were in the range of 4 ± 1.4% to 54 ± 10% and 1.8 ± 0.1% to 27 ± 5%, respectively, and they varied depend on the preparation method and conditions. XRD, DSC, and FTIR results revealed that although scCO2 was able to solubilise BZ, it did not change the solid-state morphology of BZ. Contrary, FD and γ-CD complexation were shown to affect the solid-state characteristics of BZ and γ-CD. The mean particle size of processed BZ was significantly reduced from 604 ± 61.50 nm (un-processed BZ) to 257 ± 41-385 ± 36.56 nm (processed BZ). Both the dissolution rate profiles and dissolution efficiency differed depending on preparation methods, process conditions, and BZ-to-γ-CD ratio, but they were significantly increased compared to un-processed BZ. Overall, this study demonstrated that the preparation methodology had substantial effects on the solid-state particle size/morphology characteristics and aqueous dissolution behaviour of BZ, both alone or in complexes with γ-CD, with potential to develop improved formulations.Interest in 3D-printing technologies for pharmaceutical manufacturing of oral dosage forms is driven by the need for personalized medicines. Most research to date has focused on printing of polymeric-based drug delivery systems at high temperatures. Furthermore, oral formulation development is continuously challenged by the large number of poorly water-soluble drugs, which require more advanced enabling formulations to improve oral bioavailability. In this work, we used semi-solid extrusion (SSE) printing of emulsion gels with three types of emulsified lipid-based formulations (LBFs) to produce solid lipid tablets incorporating the poorly water-soluble drug, fenofibrate. Tablets were successfully 3D-printed from emulsion gels using SSE at room temperature, making the methodology particularly useful for thermolabile compounds. The tablets were well-defined in mass and disintegrated rapidly ( less then 15 min). Importantly, the oil droplet size reconstituted after dispersion of the tablets and subsequent lipid digestion was similar to traditional liquid LBFs. This work demonstrates the successful use of SSE for fabricating solid lipid tablets based on emulsion gels. The method is further promising for on demand production of personalized dosage forms, necessary for flexible dosage adjustment in e.g., pediatric patients, when poorly water-soluble compounds constitute the core of the therapy.There has been a growing and evolving research to find a treatment or a prevention against coronavirus 2019 (COVID-19). Though mass vaccination will certainly help in reducing number of COVID-19 patients, an effective therapeutic measure must be available too. Intravenous remdesivir (RDV) was the first drug receiving Food and Drug Administration (FDA) approval for the treatment of COVID-19. However, in a pandemic like COVID-19, it is essential that drug formulations are readily available, affordable and convenient to administer to every patient around the globe. In this study, we have developed a Self-injectable extended release subcutaneous injection of Remdesivir (SelfExRem) for the treatment of COVID-19. As opposed to intravenous injection, extended release subcutaneous injection has the benefits of reducing face-to-face contact, minimizing hospitalization, reducing dosing frequency and reducing overall health care cost. SelfExRem was developed using a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), dissolved in a biocompatible vehicle. Six different batches were formulated using 2 different grades of low molecular weight PLGA and 3 different PLGA concentration. The force of injection of various polymeric solutions through 23-30-gauge needles were analyzed using a TA.XTplus texture analyzer. The time required for injection was evaluated both manually and by using an autoinjector. In vitro release of all the batches were carried out in 1% v/v tween 80 in phosphate buffer saline. The study indicated that SelfExRem developed with15% w/v PLGA(7525) provided a steady release of drug for 48 h and may be a breakthrough approach for the treatment of COVID-19.Properties regarding stratum corneum (SC), the outermost membrane of the skin, remain an active area in dermatologic and cosmetic research. The reduced thickness of SC is associated with varied adverse statuses such as skin lipid deficiency, skin barrier dysfunctions and skin deceases, etc. Emulsifiers with existing irritative effects on skin components also face the risk of decreasing SC thickness. We have been focusing on the effects of PEGylated emulsifiers on the skin and have an interest in finding the role of their polyethylene glycol (PEG)-chain length in tuning skin irritations. With this aim, PEG-stearyl ethers with different numbers of hydrophilic chains were applied on the skin, and their influence on skin thickness was discovered to determine their skin barrier effect. Confocal Raman spectroscopy (CRS) with extensive application in skin research was used here. To obtain the precise determination of skin thickness, our secondary aim was to find the optimal CRS configuration referring to varied objectives and pinhole sizes where further study is still in demand. Therefore, SC thickness measured via eddy current approach served as reference. The applied PEG-stearyl ethers formed the system to achieve varied thicknesses. Results confirmed that the skin interactions rose with increasing PEG-chain length, however only up to a certain limit, with decreasing effects recorded from PEG-40 stearyl ether and no effects observed from PEG-100 stearyl ether. Simultaneously, CRS combined with water immersion objective and 50 μm pinhole presented the most consistent values to the references and exhibited better spectral intensity and signal-to-noise ratio. Correlation plots involving different cases of configurations were calculated for error corrections. Taken together, this work helps to identify the potential mechanisms governing the interactions between PEG-stearyl ethers and skin and offers powerful evidence of using CRS as a reliable alternative to obtain accurate thickness values.The prodrug approach targeting influx transporters has been extensively studied as a means of central nervous system drug delivery. Transporter and enzyme expression, localization and activity may contribute to significant species differences in preclinical studies. However, data about the possible species differences in the intra-brain distribution of transporter utilizing compounds is scarce. Here, we investigated the species differences in the intra-brain distribution of an L-type amino acid transporter 1 (LAT1)-utilizing L-lysine analogue of ketoprofen (KPF) (compound 1) and KPF itself by the whole tissue and brain microdialysis methods in mice, and compared the results to those previously reported in rats. Their pharmacodynamic responses in both species were assessed by measuring the brain prostaglandin E2 (PGE2) levels by LC-MS/MS. The intracellular delivery of compound 1 was much lower in mice than in rats. Higher target site concentrations of compound 1 and released KPF were reflected on a more pronounced effect on PGE2 levels in the rat brain. In conclusion, these results highlight the need for cross-species characterization of prodrug pharmacokinetics and pharmacodynamics in preclinical studies.Almost all studies on non-invasive topical drug delivery to the eye have emphasized the importance of biological barriers, static membrane barriers such as the cornea and the conjunctiva/sclera and dynamic barriers such as the lacrimal drainage. Hardly any have discussed the importance of the thermodynamic activity of the permeating drug molecules. Most drugs permeate from the eye surface into the eye by passive diffusion where, according to Fick's first law, the drug concentration gradient over the various permeation barriers (e.g., the tear fluid and the lipophilic membrane barriers) is the driving force. At the barrier interphases the dissolved drug molecules must partition from one barrier to another. For example, at the tear-cornea interphase the drug molecules must partition from the aqueous exterior into the lipophilic membrane. The drug partition coefficient between two phases is commonly defined as the equilibrium concentration ratio. However, these are only approximations. The actual driving force in Fick's first law is the gradient of the chemical potential and the equilibrium between two phases is attained when the chemical potential of the drug in one phase is equal to that in the other phase.
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