Traditional Chinese medicine (TCM) has been practiced for thousands of years with a recent increase in popularity. Despite promising biological activities of active ingredients and fractions from ...TCM, their poor solubility, poor stability, short biological half-life, ease of metabolism and rapid elimination hinder their clinical application. Therefore, overcoming these problems to improve the therapeutic efficacy of TCM preparations is a major focus of pharmaceutical sciences. Recently, nanocarriers have drawn increasing attention for their excellent and efficient delivery of active TCM ingredients or fractions. This review discusses problems in the delivery of active TCM ingredients or fractions; focuses on recent advances in nanocarriers that represent potential solutions to these problems, including lipid-based nanoparticles and polymeric, inorganic, and hybrid nanocarriers; and discusses unanswered questions in the field and criteria for the development of better nanocarriers for the delivery of active TCM ingredients or fractions to be focused on in future studies.
Performance of nanocarriers in delivering active ingredients or fractions from TCM Display omitted
•Improving efficacy of TCM preparations is a challenge in pharmaceutical sciences.•Goals in nanocarries to deliver active TCM ingredients or fractions are reviewed.•Nanocarriers are efficient in delivering active TCM ingredients or fractions.•This review focuses on recent advances in various nanocarriers.•The remaining questions and criteria for the desirable nanocarriers are discussed.
Erythrocytes (red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems (DDS) because of their features of biocompatibility, ...biodegradability, and long circulating half-life. Accordingly, a "camouflage" comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed, providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems.
The objective of this study was to develop self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble drug, oridonin. The influence of the ...oil, surfactant and co-surfactant types on the drug solubility and their ratios on forming efficient and stable SMEDDS were investigated in detail. The SMEDDS were characterized by morphological observation, droplet size and zeta-potential determination, cloud point measurement and
in vitro release study. The optimum formulation consisted of 30% mixture of Maisine 35-1 and Labrafac CC (1:1), 46.7% Cremopher EL, and 23.3% Transcutol P.
In
vitro release test showed a complete release of oridonin from SMEDDS in an approximately 12
h. The absorption of oridonin from SMEDDS showed a 2.2-fold increase in relative bioavailability compared with that of the suspension. Our studies demonstrated the promising use of SMEDDS for the delivery of oridonin by the oral route.
The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of tumours. Ferroptosis, resulting from the iron-dependent accumulation of lipid peroxides, has the ...potential to reverse multidrug resistance. However, simultaneous delivery of the iron sources, ferroptosis inducers, drugs, and enhanced circulation carriers within matrices remains a significant challenge. Herein, we designed and fabricated a defect self-assembly of metal-organic framework (MOF)-red blood cell (RBC) membrane-camouflaged multi-drug-delivery nanoplatform for combined ferroptosis-apoptosis treatment of multidrug-resistant cancer. Ferroptosis and chemotherapeutic drugs are embedded in the centre of the iron (III)-based MOF at defect sites by coordination with metal clusters during a one-pot solvothermal synthesis process. The RBC membrane could camouflage the nanoplatform for longer circulation. Our results demonstrate that this defect self-assembly-enabled MOF-membrane-camouflaged nanoplatform could deplete the glutathione, amplify the reactive oxidative species oxidative stress, and enable remarkable anticancer properties. Our work provides an alternative strategy for overcoming multidrug resistance, which could regulate the fluidity and permeability of the cell membrane by ferroptosis to downregulate of P-glycoprotein protein expression by ferroptosis. This defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform has great therapeutic potential.
The defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform provides simultaneous delivery of iron sources, ferroptosis inducers and guest drugs during a one-pot solvothermal synthesis process. The embedded complexation within defect nanostructures can prevent unexpected drug leakage. Ferroptosis is driven by oxidative phospholipid damage, which could downregulate P-gp protein expression and then reduce drug resistance. Display omitted
•Fabricated a defect self-assembly-enabled MOF.•Ferroptosis-inducing reverse multidrug resistance.•MOF-membrane-camouflaged multi-drug-delivery nanoplatform.•Ferroptosis-apoptosis treatment of multidrug-resistant cancer therapy.
Ischemic stroke is a common disease threatening human health. ADAMTS9-AS2 is a lncRNA that has been widely studied in tumors, but not in ischemic stroke. The purpose of this study was to investigate ...the role and potential molecular mechanism of ADAMTS9-AS2 in endothelial cell function after ischemic stroke in vivo and in vitro. The results showed that ADAMTS9-AS2 was decreased in the plasma of acute ischemic stroke (AIS) patients and in the brain tissue and plasma of MCAO mice, and the low expression of ADAMTS9-AS2 was associated with the increase in infarct size. Besides, compared with the control group, MCAO treatment slightly promoted angiogenesis, which was enhanced by the overexpression of ADAMTS9-AS2. Molecular mechanism results indicated that ADAMTS9-AS2 and miR-185-5p affected the pathological process of ischemic stroke through ceRNA mechanism, and IGFBP-2 was a downstream target gene of miR-185-5p. These findings demonstrated that ADAMTS9-AS2 promoted angiogenesis through regulating miR-185-5p/IGFBP-2 axis, suggesting that ADAMTS9-AS2 may be a potential marker for the diagnosis and treatment of neurological diseases.
Similar to blood, interstitial fluid (ISF) contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis. However, current ISF extraction techniques require bulky ...instruments and are both time-consuming and complicated, which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles. Currently, microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis. The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring, while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification. Herein, we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.
Display omitted
•The advances in microneedle-assisted interstitial fluid extraction for drug analysis are reviewed.•The microneedles-mediated wearable devices for diagnosis and treatment are discussed.•Microneedles for in vivo sampling from living herbs are described.
Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the ...solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of ~25 nm and vertical distance of ~1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.
Melittin is a promising antitumor substance; however, it is a nonspecific cytolytic peptide, which limits its clinical application. In this study, melittin liposomes (Mel-Lip) and hyaluronic acid ...(HA)-modified Mel-Lip (Mel-HA-Lip) were designed to reduce the toxicity and increase the anti-tumor effects of melittin. The optimal preparation procedure was evaluated using a uniform design based on the single factor method, and the concentration of HA was determined based on the cellular uptake of coumarin 6 labeled HA-Lip. Liposomes and HA-modified liposomes were evaluated in vitro by assessing cytotoxicity, cellular uptake, and release behavior. Liposomes prepared in the optimum formulation improved stability, with a particle size of 132.7 ± 1.55 nm, zeta potential of −11.5 ± 1.51 mV, entrapment efficiency of 86.25 ± 1.28%, and drug-loading efficiency of 3.91 ± 0.49%. Cellular uptake tests revealed that the uptake of nanoparticles significantly increased with HA modification, suggesting that HA modification enhanced the internalization of liposomes within cells, which was consistent with the results of the cytotoxicity analysis. Furthermore, in vitro release experiments showed that Mel-HA-Lip possessed a stronger sustained-release effect compared with Mel-Lip. The results of this experiment provide insight into the potential tumor-targeting effects of melittin.
In this study, the skin permeation of liposomes containing psoralen was investigated by in vivo skin microdialysis. Psoralen-loaded nano-sized liposomes were prepared with a mean size of 117.5 nm and ...a polydispersity index of 0.21, indicating the uniform dispersion of phosphatidylcholine vesicles in the liposomal solution. Based on in vivo microdialysis experiments, the drug concentration in local deep skin of rat increased rapidly and reached a peak concentration (Cmax) of 319.35±23.72 µg/mL at 180 min, and decreased slowly thereafter. The local area under the concentration–time curve (AUC)0–t was 3.81-fold higher than the compared aqueous suspension. The in vivo systemic pharmacokinetics were in agreement with the microdialysis results, in view of the Cmax and AUC0–t from liposomal group were both significantly higher (p<0.05) than the compared group. Liposome-associated transdermal psoralen delivery was significantly more effective than delivery via an aqueous suspension. The enhanced skin permeability may be associated with improved skin hydration, lipid exchange and fusion with the stratum corneum (SC), and changes in SC structure, promoting drug permeation into deep skin. After 10 h of treatment with the perfusate, the microstructure of the microdialysis probe exhibited no obvious differences with control probes. The skin surface and the tissue around the probe showed no swelling or inflammation. These findings indicated that liposomes effectively enhanced the skin deposition of psoralen and showed good biocompatibility with skin tissues; additionally, ethanol at a low concentration in ringer’s solution is an alternative perfusate for in vivo skin microdialysis studies.
Background:
Alzheimer’s disease (AD) is the most common form of dementia in old age and poses a severe threat to the health and life of the elderly. However, traditional diagnostic methods and the ...ATN diagnostic framework have limitations in clinical practice. Developing novel biomarkers and diagnostic models is necessary to complement existing diagnostic procedures.
Methods:
The AD expression profile dataset GSE63060 was downloaded from the NCBI GEO public database for preprocessing. AD-related differentially expressed genes were screened using a weighted co-expression network and differential expression analysis, and functional enrichment analysis was performed. Subsequently, we screened hub genes by random forest, analyzed the correlation between hub genes and immune cells using ssGSEA, and finally built an AD diagnostic model using an artificial neural network and validated it.
Results:
Based on the random forest algorithm, we screened a total of seven hub genes from AD-related DEGs, based on which we confirmed that hub genes play an essential role in the immune microenvironment and successfully established a novel diagnostic model for AD using artificial neural networks, and validated its effectiveness in the publicly available datasets GSE63060 and GSE97760.
Conclusion:
Our study establishes a reliable model for screening and diagnosing AD that provides a theoretical basis for adding diagnostic biomarkers for the AD gene.
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