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This study provides a graphical solution for the management of process scale-up and scale-down between both types of product containers depending on their respective KV and product resistance to mass transfer.Toxic and environmental harmful organic solvents are widely applied to prepare poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NP) in standard preparation methods. Alternative non-toxic solvents suffer from disadvantages like high viscosity and plasticizing effects. To overcome these hurdles, Cyrene™ as a new sustainable, non-toxic and low viscous solvent was used to formulate PLGA NPs. A new preparation method was developed and optimized. Small sized blank NPs around 220 nm with a narrow size distribution and highly negative charge ( less then -23 mV) were obtained. To test the application for drug delivery, the lipophilic model drug atorvastatin was encapsulated in high drug loads with comparable physicochemical characteristics as the blank NPs, and a total drug release within 24 h. No changes of the crystallinity or plasticizing effects could be observed. Highly purified NPs were obtained with a residual Cyrene™ content less then 2.5%. Finally, the biocompatibility of Cyrene™ itself and of the NPs formed in the presence of Cyrene™ was demonstrated in a hen's egg test. Conclusively, the use of Cyrene™ as solvent offers a simple, fast and non-toxic procedure for preparation of PLGA NPs as drug delivery systems circumventing the downsides of standard methods.Despite the advantages of transdermal drug delivery (TDD), which makes it a fast-growing area of research in pharmaceutics, numerous challenges affect their development, which limits exploring the full potential of this alternate drug delivery route. In trying to address one of these problems, it is strongly believed that the need for a sustainable skin alternative is paramount. Efforts made in an attempt to provide a sustainable alternative to employing skin in pharmaceutical analysis, by better utilising a polymer membrane, namely poly(dimethylsiloxane), also known as PDMS are discussed. Several combined properties of this polymer, which includes its relative stability in comparison with human skin, make it a good candidate for the replacement of skin. Modifications undertaken to this polymer membrane (to create an enhanced skin mimic for permeation analysis) are discussed and reviewed in this paper, including the improved ability to predict permeability for both hydrophobic and hydrophilic drugs. Optimisations related to studying TDD including limitations encountered are also documented and reviewed. It is hoped that such developments in this field will ultimately lead to researchers replacing skin with optimised polymer-based alternatives to predict transdermal drug delivery.
Acute lung injury (ALI) is characterized by alveolar macrophage overactivation and uncontrolled pulmonary inflammation. Mitochondrial damage-associated molecular patterns (MTDs), one type of damage-associated molecular patterns (DAMPs) released from ruptured mitochondrial, can induce inflammation which participates in the pathogenesis of ALI. Despite the critical role of autophagy in inflammatory response, little is known about its function in MTDs-induced ALI. Herein we have studied how autophagy attenuates MTDs-induced ALI in vitro and in vivo.
Exogenous MTDs were injected into mice through tail vein injection or directly treated with cultured alveolar macrophage cell lines to construct MTDs-induced ALI models. Immunology inhibitor Rapamycin and 3-MA were used to regulate autophagy in vivo and in vitro. The expressions of Caspase-1, IL-1β, and their precursor were measured. Inhibition the activation of NLRP3 inflammasome to discover the candidate targets and potential molecular pathways involved in autophagy mitigating the pression level of NLRP3 inflammasome-associated proteins were greatly decreased in MTDs-induced mouse model. MTDs-induced inflammation and lung injury were alleviated by autophagy enhancement. Autophagy can function as an effective way to alleviate inflammation in MTDs-induced ALI by inhibiting NLRP3 inflammasome and may represent a therapeutic target in modulating MTDs-induced inflammatory response.
Ischemic renal disease (IRD) can cause kidney damage and eventually lead to end-stage renal disease. Adiponectin (APN), a recently discovered collagen-like protein secreted by adipose tissues, plays an important role in regulating energy metabolism and inflammation. This study aimed to explore the specific mechanism by which APN affects IRD.
We cultured human renal tubular epithelial cells (HK-2) and created a mouse model of IRD to detect apoptosis-related indicators in vitro and in vivo.
Compared with those in the control group, the apoptosis rate and expression levels of Bax and Fas increased in the CoCl
-induced hypoxia model group. However, the expression of Bcl-2 decreased, and after the combined treatment with APN, the phenomenon mentioned above was reversed. Moreover, studies have found that stanniocalcin-1 (STC-1) and uncoupling protein3 (UCP3) are also involved in the protective effect of APN. Additionally, we found that the glomeruli of the mice were significantly enlarged after the APN gene was knocked out; furthermore, the number of collagen fibers in the renal tubules, as well as the expression of the corresponding fibrogenic factors, increased significantly. More importantly, after the knockout of the APN gene, the expression of the hypoxia-inducible factors HIF-1α and HIF-1β and the apoptotic rate of renal tissue cells also increased.
These results indicate that APN can alleviate the symptoms of IRD by inhibiting renal cell apoptosis. Thus, in the future, APN may be a new target for the treatment of IRD.
Cobalt chloride (PubChem CID 24643).
Cobalt chloride (PubChem CID 24643).Liver regeneration after partial hepatectomy (PH) is a complex and well-orchestrated process involving multiple factors such as cytokines, growth factors, and signaling pathways. MicroRNAs (miRNAs) participate in various biological processes including liver regeneration after PH. In the current study, we investigated the expression and function of human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived exosomal miRNAs on liver regeneration using a rat PH model. We found that hUCB-MSC derived exosomes promoted rat liver regeneration and ameliorated liver injury after PH. MicroRNA microarray was performed to identify the differentially expressed miRNAs in hUCB-MSC derived exosomes involving in liver regeneration after PH. We demonstrated that hUCB-MSC derived exosomal miR-124 could promote liver regeneration and prevent against liver injury after PH in rats. Inhibition of miR-124 abrogated the protective role of hUCB-MSC derived exosome in rat liver regeneration after PH. In addition, we identified that transcription factor Foxg1 was a direct target of miR-124 and miR-124 promoted rat liver cell proliferation via suppressing Foxg1 expression.
Homepage: https://www.selleckchem.com/products/1400w.html
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