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DOP-DEDA LNP encapsulating siRNA against polo-like kinase 1 (siPLK1) highly suppressed the expression of PLK1 mRNA and its protein. The cellular uptake of DOP-DEDA LNP was increased in an apolipoprotein E3 (apoE3) dose-dependent manner. In addition, DOP-DEDA LNP was taken up into cancer cells via both clathrin- and caveola-mediated endocytosis pathways. These findings indicate that LNP composed of this charge-reversible lipid should be a highly stable and potent siRNA delivery vector.In this study, microemulsions capable of transforming into nanostructured hexagonal phase gels in vivo upon uptake of biological fluids for naltrexone prolonged release were investigated as a strategy for management of alcohol use disorder (AUD). Microemulsions were prepared using monoolein, tricaprylin, water and propylene glycol; after preliminary characterization, one formulation was selected, which contained 55% of monoolein-tricaprylin (M-55). This microemulsion displayed size below 200 nm and Newtonian rheological behavior. Liquid crystalline gels formed in vitro upon 8 h of contact with water following a second order kinetics. After 120 h, less then 50% of naltrexone was released in vitro independently on drug loading (5 or 10%). In vivo, gels formed within 24 h of M-55 subcutaneous administration, and persisted locally for over 30 days providing slow release of the fluorescent marker Alexa fluor compared to a solution. Using the conditioned place preference paradigm, a test used to measure drug’s rewarding effects, a single dose of M-55 containing 5% naltrexone reduced the time spent in the ethanol-paired compartment by 1.8-fold compared to saline; this effect was similar to that obtained with daily naltrexone injections, demonstrating the formulation efficacy and its ability to reduce dosing frequency. A more robust effect was observed following administration of M-55 containing 10% of naltrexone, which was compatible with aversion. These results support M-55 as a platform for sustained release of drugs that can be further explored for management of AUD to reduce dosing frequency and aid treatment adherence.Antimicrobial resistance (AMR) has become a global health problem. Bacteria are able to adapt to different environments, with the presence or absence of a host, forming colonies and biofilms. In fact, biofilm formation confers chemical protection to the microbial cells, thus making most of the conventional antibiotics ineffective. Prevention and destruction of biofilms is a challenging task that should be addressed by a multidisciplinary approach from different research fields. One of the medical strategies used against biofilms is the therapy with drug delivery systems. Lipidic nanovesicles are a good choice for encapsulating drugs, increasing their pharmacodynamics and reducing side effects. These soft nanovesicles show significant advantages for their high biocompatibility, physical and chemistry properties, good affinity with drugs, and easy route of administration. This review summarizes the current knowledge on different types of vesicles which may be used as antibiotic carriers. The main preparation and purification methods for the synthesis of these vesicles are also presented. The advantages of drug encapsulation are critically reviewed. In addition, recent works on endolysin formulations as novel, “greener” and efficient antibiofilm solution are included. This paper can provide useful background for the design of novel efficient formulations and synergistic nanomaterials and could be also useful at the pharmaceutical industry to develop wastewater treatments and reduce the antibiotics in the environmental waters.Ethnopharmacological relevance Peach kernel (taoren TR) is the dried mature seed of peach, Prunus persica (L.) Batsch, which belongs to the Rosaceae family. Rhubarb (dahuang DH) is the dried root and rhizome of rhubarb (Rheum palmatum L., Rheum officinale Baill., or Rheum tanguticum Maxim. ex Balf.). TR-DH (TD) is a traditional Chinese medicine herb pair that promotes blood circulation and removes blood stasis. In recent years, TD has shown definite benefits in the cardio-cerebrovascular system, but its specific mechanism is not very clear. Aim of study The purpose of this study was to explore the mechanism by which TD affects cerebral ischaemia/reperfusion (I/R) injury and to optimize the mixture ratio. Methods The affected metabolic pathways in rat brain tissues after I/R were analysed by network pharmacology and verified with animal pharmacological experiments. Results TD had a certain therapeutic effect on cerebral I/R injury. TD with a TRDH ratio of 11 had the best therapeutic effect. selleck Metabolic pathway analysis showed that the protective mechanism of TD against I/R injury involves mainly regulation of brain tissue ADORA2A protein levels and action on the arachidonic acid (AA) pathway. Conclusion TD can ameliorate cerebral I/R injury by regulating ADORA2A degradation in the AA metabolic pathway to attenuate AA metabolic dysfunction and the inflammatory response.Ethnopharmacological relevance Diminished ovarian reserve (DOR) can lead to poor fertility and shorten the reproductive lifespan of female. The Dingkun Pill (DKP), a traditional Chinese-patented medication has been an integral part of Chinese treatment for centuries for the management of gynecological diseases. Relevant clinical studies have shown that DKP is able to protect against DOR, however, its mechanism of action is not yet fully known. Study goals This experiment seeks to explore the impact of tripterygium wilfordii polyglycosidium (TWP) on the PI3K/AKT/mTOR pathway in the context of the pathophysiology of DOR and the mechanism of action of DKP. Materials and methods Eighty female Balb/c mice with regular estrous cycle were divided into Blank, Model, DKP and hormone replacement therapy (HRT) group by random. With the exception of the Blank group, mice from other groups were exposed to 40 mg/kg/d TWP suspension for 30 days to induce DOR. Following this, either DKP or hormones were orally administrated e to improve levels of serum hormones and promote recovery of a normal estrous cycle. DKP augmented the total amount of primordial follicles while reducing the total follicles that were atretic follicles. The apoptosis index of growing follicles and Bax, Cyt C and Caspase-3 expressions were also decreased while increasing the Bcl-2 Bax ratio. DKP suppressed levels of the phosphorylation and mRNA expressions of mTOR, AKT and PI3K. Conclusion DKP was demonstrated to increase ovarian reserve through inhibition of the PI3K/AKT/mTOR signaling pathway, leading to suppression of primordial follicle activity and reduction in apoptosis of early growing follicles. This highlights its potentially useful role in the treatment of DOR.