Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model.

Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood-brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/ß-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain-blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/ß-catenin pathway.

HA-Coated PLGA Nanoparticles Loaded with Apigenin for Colon Cancer with High Expression of CD44.

Apigenin (API) possesses excellent antitumor properties but its limited water solubility and low bioavailability restrict its therapeutic impact. Thus, a suitable delivery system is needed to overcome these limitations and improve the therapeutic efficiency. Poly (lactic-co-glycolic acid) (PLGA) is a copolymer extensively utilized in drug delivery. Hyaluronic acid (HA) is a major extracellular matrix component and can specifically bind to CD44 on colon cancer cells. Herein, we aimed to prepare receptor-selective HA-coated PLGA nanoparticles (HA-PLGA-API-NPs) for colon cancers with high expression of CD44; chitosan (CS) was introduced into the system as an intermediate, simultaneously binding HA and PLGA through electrostatic interaction to facilitate a tighter connection between them. API was encapsulated in PLGA to obtain PLGA-API-NPs, which were then sequentially coated with CS and HA to form HA-PLGA-API-NPs. HA-PLGA-API-NPs had a stronger sustained-release capability. The cellular uptake of HA-PLGA-API-NPs was enhanced in HT-29 cells with high expression of CD44. In vivo, HA-PLGA-API-NPs showed enhanced targeting specificity towards the HT-29 ectopic tumor model in nude mice in comparison with PLGA-API-NPs. Overall, HA-PLGA-API-NPs were an effective drug delivery platform for API in the treatment of colon cancers with high expression of CD44.

Soft materials as biological and artificial membranes.

The past few decades have seen emerging growth in the field of soft materials for synthetic biology. This review focuses on soft materials involved in biological and artificial membranes. The biological membranes discussed here are mainly those involved in the structure and function of cells and organelles. As building blocks in medicine, non-native membranes including nanocarriers (NCs), especially liposomes and DQAsomes, and polymeric membranes for scaffolds are constructed from amphiphilic combinations of lipids, proteins, and carbohydrates. Artificial membranes can be prepared using synthetic, soft materials and molecules and then incorporated into structures through self-organization to form micelles or niosomes. The modification of artificial membranes can be realized using traditional chemical methods such as click reactions to target the delivery of NCs and control the release of therapeutics. The biomembrane, a lamellar structure inlaid with ion channels, receptors, lipid rafts, enzymes, and other functional units, separates cells and organelles from the environment. An active domain inserted into the membrane and organelles for energy conversion and cellular communication can target disease by changing the membrane's composition, structure, and fluidity and affecting the on/off status of the membrane gates. The biological membrane targets analyzing pathological mechanisms and curing complex diseases, which inspires us to create NCs with artificial membranes.

Anti-apoptosis effect of polysaccharide isolated from the seeds of Cuscuta chinensis Lam on cardiomyocytes in aging rats.

To investigate the mechanism of apoptosis in myocardial cells of aging rats induced by D-galactose and to study the effect of the Polysaccharide isolated from the seeds of Cuscuta chinensis Lam (PCCL) on apoptosis of cardiomyocytes and its corresponding machinasim in aging rat model. Fifty male SD rats were randomly divided into 5 groups. Normal control group (NC). D-galactose (100 mg · kg(-1)d(-1) for 56 day) indued aging group (MC), D-galactose plus 100 mg kg(-1) d(-1) PCCL group (ML), D-galactose plus 200 mg kg(-1) d(-1) PCCL group (MM), and D-galactose plus 400 mg kg(-1) d(-1) PCCL group (MH). Same volume of solution (water, or PCCL aqueous solution) was given by gavage for 56 days. Then the hearts were collected and apoptosis parameters were evaluated. Caspase-3 and Cyt c were determined by fluorescence spectrometer, the apoptosis rate was assessed by AnnexinV-FITC method by Flow-Cytometry, [Ca(2+)]i and [Ca(2+)]i overloaded by KCL were observed by laser scanning confocal microscopy (LSCM); Bcl-2 and Bax were examined by immunohistochemistry. The content of Cyt C, [Ca(2+)]i of cardiomyocytes, the activity of Caspase-3, Bax expression level in D-galactose induced aging group were higher than NC (p < 0.05). The ratio of Bcl-2/Bax was decreased in D-galactose induced aging group compared to NC. On the other hand, the content of Cyt C, [Ca(2+)]i of cardiomyocytes, the activity of Caspase-3 and apoptosis rate, as well as Bax expression level in all three PCCL groups were decreased compared to galactose induced group (p < 0.05). Bcl-2/Bax ratio was increased in all PCCL groups compared to galactose induced aging group. PCCL could decrease the apoptosis of cardiomyocytes by the mitochondria apoptosis pathway.

Functional nanoparticles in targeting glioma diagnosis and therapies.

Successful therapy and diagnosis of glioma is one of the biggest challenges in the biomedical fields. The incidence is growing gradually around the world. Annually, there are approximately 13,000 cases of glioblastoma multiforme diagnosed with historical 1-year and 5-year survival rates of 29.3% and 3.3%, respectively. The prognosis of patients with malignant glioma remains dismal. Due to its highly proliferative, infiltrative, and invasive property, development of effective preventative strategies to control the gliomas is in high demand. Meanwhile, the efficiency of drug delivery to glioma remains low owing to the non-specific, non-targeted nature of anti-tumor agents. Furthermore, the presence of the blood brain barrier and blood brain tumor barrier is another obstacle for gliomas treatments. Nanotechnology has brought a paradigm shift in the diagnosis and treatment of glioma. This review discusses the potential of various nanoparticles in the diagnosis of gliomas using some metal oxide, and in the therapy of gliomas including receptor-mediated, magnetic directing, and cell-mediated drug delivery systems. In this review, some physical techniques combined with nanoparticles (NPs) such as ultrasound therapy, thermochemotherapy, photodynamic therapy, and fluorescent magnetic NPs have also been summarized.

3D printing processes in precise drug delivery for personalized medicine.

With the advent of personalized medicine, the drug delivery system will be changed significantly. The development of personalized medicine needs the support of many technologies, among which three-dimensional printing (3DP) technology is a novel formulation-preparing process that creates 3D objects by depositing printing materials layer-by-layer based on the computer-aided design method. Compared with traditional pharmaceutical processes, 3DP produces complex drug combinations, personalized dosage, and flexible shape and structure of dosage forms (DFs) on demand. In the future, personalized 3DP drugs may supplement and even replace their traditional counterpart. We systematically introduce the applications of 3DP technologies in the pharmaceutical industry and summarize the virtues and shortcomings of each technique. The release behaviors and control mechanisms of the pharmaceutical DFs with desired structures are also analyzed. Finally, the benefits, challenges, and prospects of 3DP technology to the pharmaceutical industry are discussed.

MicroRNA-195 liposomes for therapy of Alzheimer's disease.

The complex etiologies and mechanisms of Alzheimer's disease (AD) underscore the importance for devising multitarget drugs to achieve effective therapy. MicroRNAs (miRNAs) are capable of concurrently regulating the expression of multiple proteins by selectively targeting disease- associated genes in a sequence-specific fashion. Nonetheless, as RNA-based drugs, their stability in the circulation and capacity of traversing the blood-brain barrier (BBB) is largely compromised, thereby limiting their potential clinical applications. In this study, we formulated the nanoliposomes encapsulating polyethyleneimine (PEI)/miR-195 complex (DPMT@PEI/miR-195) that was engineered through dual modifications to contain P-aminophenyl-alpha-d-mannopyranoside (MAN) and cationic cell-penetrating peptide (TAT). DPMT@PEI/miR-195 exhibited the enhanced BBB- and cell membrane penetrating capability. As expected, we observed that DPMT@PEI/miR-195 administered through intravenous tail injection of produced greater effectiveness than donepezil and the same range of effect as aducanumab in alleviating the cognitive decline in 7-month-old APP/PS1 mice. Moreover, the combination treatment with DPMT@PEI/miR-195 and donepezil effectively ameliorated the deterioration of cognition in 16-month-old APP/PS1 mice, with enhanced effects than either DPMT@PEI/miR-195 or donepezil alone. Furthermore, DPMT@PEI/miR-195 effectively attenuated the positive signals of Aß, AT8, and CD68 in APP/PS1 mice without notable side effects. Our findings indicate DPMT@PEI/miR-195 as a promising potentially new agent or approach for the prophylaxis and treatment of early and advanced stages of Alzheimer's disease.

Lentivirus-mediated CD/TK fusion gene transfection neural stem cell therapy for C6 glioblastoma.

A suicide gene can convert nontoxic prodrugs into toxic products to kill tumor cells. In this study, our aim was to transfect lentivirus-mediated CD/TK fusion gene into Wistar rat's neural stem cells (NSC) and then implant the NSC into a C6 glioma model to observe a C6 glioma growth inhibition effect. Primary NSC and stable transfection CD/TK fusion gene cell lines were established. To observe the tumor size and rat survival period in different groups, C6 glioma cell apoptosis and cell viability rate were applied to analyze the tumor inhibition effect of the neural stem cells' transfected CD/TK fusion gene. C6 cell viability showed that CDglyTK-NSC + GCV/5-Fc (group 1) was lower than CDglyTK-NSC (group 2), NSC + GCV/5-Fc (group 3), and control (group 4) from day 2 (p < 0.05), and the apoptosis rate was higher in group 1 compared with that of other groups (50.6%, p < 0.05) either in vitro or in vivo (35.47%, p < 0.05); both cell viability and apoptosis had no significance in the other three groups. In vivo, tumor size in group 1 was 7.76 ± 1.37 mm(3), which is smaller than the others (group2 27.28 ± 4.11 mm(3), group3 27.94 ± 2.08 and 28.61 ± 2.97 mm(3); p < 0.05). The other groups' tumor size was not significant (p > 0.05). Survival time of rats treated with CDglyTK-NSC + GCV/5-Fc (group 1) was significantly longer than that of the other groups (p < 0.05; group 1 48.86 ± 1.97, group 2 28.67 ± 3.75, group 3 31.5 ± 1.27, group 4 29.3 ± 1.33). We also showed that the transfected C6 cells had a migratory capacity toward gliomas in vivo. Transfected CD/TK fusion gene neural stem cells combined with propyl-guanosine and 5-flucytosine double prodrug significantly inhibit the development of glioma.

Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4.

Myocardial fibrosis can lead to ischemic damage of the myocardium, which can be life-threatening in severe cases. Cardiac fibroblast (CF) transdifferentiation is an important process in myocardial fibrosis. Fucoxanthin (FX) plays a key role in ameliorating myocardial fibrosis; however, its mechanism of action is not fully understood. This study investigated the role of FX in the angiotensin II (Ang II)-induced transdifferentiation of CFs and its potential mechanisms of action. We found that FX inhibited Ang II-induced transdifferentiation of CFs. Simultaneously, FX downregulated bromodomain-containing protein 4 (BRD4) expression in CFs and increased nuclear expression of nuclear factorerythroid 2-related factor 2 (Nrf2). FX reverses AngII-induced inhibition of the Keap1/Nrf2/HO-1 pathway and elevates the level of reactive oxygen species (ROS). FX failed to reverse Ang II-induced changes in fibrosis-associated proteins and ROS levels after Nrf2 silencing. BRD4 silencing reversed the inhibitory effect of Ang II on the Keap1/Nrf2/HO-1 antioxidant signalling pathway. In conclusion, we demonstrated that FX inhibited Ang II-induced transdifferentiation of CFs and that this effect may be related to the activation of the Keap1/Nrf2/HO-1 pathway by reducing BRD4 expression and, ultimately, oxidative stress.

Challenges and opportunities in delivering oral peptides and proteins.

INTRODUCTION: Rapid advances in bioengineering enable the use of complex proteins as therapeutic agents to treat diseases. Compared with conventional small molecule drugs, proteins have multiple advantages, including high bioactivity and specificity with low toxicity. Developing oral dosage forms with active proteins is a route to improve patient compliance and significantly reduce production costs. However, the gastrointestinal environment remains a challenge to this delivery path due to enzymatic degradation, low permeability, and weak absorption, leading to reduced delivery efficiency and poor clinical outcomes. AREAS COVERED: This review describes the barriers to oral delivery of peptides and complex proteins, current oral delivery strategies utilized and the opportunities and challenges ahead to try and circumvent these barriers. Oral protein drugs on the market and clinical trials provide insights and approaches for advancing delivery strategies. EXPERT OPINION: Although most current studies on oral protein delivery rely on in vitro and in vivo animal data, the safety and limitations of the approach in humans remain uncertain. The shortage of clinical data limits the development of new or alternative strategies. Therefore, designing appropriate oral delivery strategies remains a significant challenge and requires new ideas, innovative design strategies and novel model systems.

The liposomal daunorubicin plus tamoxifen: improving the stability, uptake, and biodistribution of carriers.

The synergistic effects of tamoxifen on the sensitivity of MCF-7 cells to daunorubicin have been reported. Whether the effects of daunorubicin on MCF-7/adr cells can be improved by tamoxifen in liposomes and how tamoxifen changes daunorubicin's behavior in vivo remains unclear. The aim of this study was to investigate the effects of tamoxifen on the uptake and biodistribution of daunorubicin liposomes by breast-cancer-resistant MCF-7/adr cells in vitro and in vivo. The uptake of liposomes by MCF-7/adr cells in vitro studies was measured using flow cytometry and laser confocal microscopy. The biodistributions of carriers and free drugs were evaluated by DiR dye using in vivo imaging. Tamoxifen obviously enhanced the cellular uptake of liposomes by MCF-7/adr cells in time-dependent manners. According to the results from in vivo imaging analysis, the mean fluorescence intensity of DiR liposomes with tamoxifen in the tumor regions of MCF-7/adr tumor-bearing nude mice was much stronger than that of DiR liposomes alone (16,450 ± 1,331 versus 3,666 ± 321; n = 3). Pegylated liposomes elongated the existence of daunorubicin in the circulatory system and the enhanced permeability and retention effect enhanced its concentration in local tumor tissues, which may provide the precondition for tamoxifen further promoting the uptake by MCF-7/Adr cells in vivo. Using daunorubicin liposomes and tamoxifen together generates better biodistribution profiles in tumor tissue than using daunorubicin liposomes only, which contributes to improving the therapeutic effect of breast cancer treatment.

Effect of Malt-PEG-Abz@RSL3 micelles on HepG2 cells based on NADPH depletion and GPX4 inhibition in ferroptosis.

Ferroptosis is a regulated cell death pathway which depends on iron. Ferroptosis can be induced by limiting intracellular glutathione (GSH) synthesis, or inhibiting the activity of GPX4, or increasing intracellular accumulation of PE-AA-OOH, all of which involve NADPH. Therefore, NADPH depletion, excessive PE-AA-OOH, and GPX4 deficiency are generally considered to be the main characteristics of ferroptosis. In this research, the novel self-assembly nanomicelles modified by maltose ligand (Malt-PEG-Abz@RSL3) with superior nano characteristics were designed and fabricated. Malt-PEG-Abz@RSL3 micelles achieved active targeted drug delivery due to the high expression of glucose transporter (GLUT) and high uptake by HepG2 cells. Maltose-polyethylene glycol broke to release RSL3 for inhibiting GPX4 activity when Malt-PEG-Abz@RSL3 micelles entered the cells. Meanwhile, key coenzyme NADPH that participated in synthesis of GSH and Trx(SH)2 was depleted by azobenzene moiety, resulting in decreasing GSH and Trx(SH)2, which dually induced ferroptosis in tumour cells and promoted cell apoptosis.

Integrated platform of oxygen self-enriched nanovesicles: SP94 peptide-directed chemo/sonodynamic therapy for liver cancer.

Hepatocellular carcinoma (HCC) is a most common primary liver cancer among the most deadly malignancies. Selectively killing the cancer cells within the liver urgently requires the novel treatment strategies. The combination of sonodynamic therapy (SDT) and chemotherapy based on the nanotechnology have achieved some achievements in the HCC treatments. However, off-targeting drug delivery to healthy cells and the hypoxic microenvironment in the solid tumors frustrate the efforts to the combined strategy. The hypoxic microenvironment restrains the generation of ROS, leading to the decreased effects of SDT. To improve the clinical outcomes of chemo/SDT strategy, we created a novel oxygen self-enriched active targeted nanovesicle (ICG-DOX NPs/PFH@SP94-Lip). SP94 peptide could enhance the selectivity of the nanovesicles to liver tumor cells rather than normal liver cells. Besides, an oxygen carrier, perfluorohexanes (PFH), was co-loaded into liposomes to increase the oxygen level in tumor tissue, thus improving the effects of SDT. The in vivo studies showed that the ICG-DOX NPs/PFH@SP94-Lip combined with the external US stimulation significantly inhibited effects on tumor growth. Therefore, this novel oxygen self-enriched chemo/SDT nanocomposites represents a proof-of-concept liver tumor treatment strategy.

Design and evaluation of glutathione responsive glycosylated camptothecin nanosupramolecular prodrug.

A novel tumor-targeted glutathione responsive Glycosylated-Camptothecin nanosupramolecular prodrug (CPT-GL NSp) was designed and fabricated via a disulfide bond. The effects of glycoligand with different polarities on solubility, self-assembly, stability, cellular uptake, and glutathione responsive cleaving were explored, and an optimal glycosylated ligand was selected for nanosupramolecular prodrug. It has been found that CPT-GL NSp exhibited higher drug loading than traditional nanoparticles. Among of which maltose modified NSp had the strongest anti-tumor effects than that of glucose and maltotriose. CPT-SS-Maltose had a similar anti-tumor ability to Irinotecan (IR), but the superior performance in solubility, hemolysis, and uptake of HepG2 cells.

Effects of polyethylene glycol on the surface of nanoparticles for targeted drug delivery.

The rapid development of drug nanocarriers has benefited from the surface hydrophilic polymers of particles, which has improved the pharmacokinetics of the drugs. Polyethylene glycol (PEG) is a kind of polymeric material with unique hydrophilicity and electrical neutrality. PEG coating is a crucial factor to improve the biophysical and chemical properties of nanoparticles and is widely studied. Protein adherence and macrophage removal are effectively relieved due to the existence of PEG on the particles. This review discusses the PEGylation methods of nanoparticles and related techniques that have been used to detect the PEG coverage density and thickness on the surface of the nanoparticles in recent years. The molecular weight (MW) and coverage density of the PEG coating on the surface of nanoparticles are then described to explain the effects on the biophysical and chemical properties of nanoparticles.

Dual pH-responsive-charge-reversal micelle platform for enhanced anticancer therapy.

A novel nanodrug delivery system (NDDS) based on block copolymers of Poly(DEA)-block-Poly(PgMA) (PDPP) was developed to enhance in vitro cellular uptake and anticancer efficacy. pH-responsive doxorubicin (DOX) based small molecule prodrug (DOX-hyd-N3) and mPEG-N3 were co-conjugated onto PDPP via copper-catalyzed "Click chemistry" to give a dual pH-responsive polymeric prodrug (mPEG-g-PDPP-g-hyd-DOX), which could be self-assembled into core-shell polymeric micelles (M(DOX)) with particles size of 81 ± 1 nm in aqueous phase. Additionally, the pH-responsive charge-reversal, stability and drug release behaviour at different pHs were then evaluated. Moreover, the surface charge of M(DOX) could quickly convert from negative (-6.64 ± 3.37 mV) to positive (5.35 ± 1.33 mV) thanks to the protonation of Poly(DEA) moieties as the pH value decreased from 7.4 during blood circulation to 6.5 in extracellular of tumour tissues. Meanwhile, according to the cytotoxicity determined by CCK-8 assay, cellular uptake, flow-cytometric and apoptosis profiles of two human cancer cell lines (HeLa and SW480), we could draw the conclusion that the cellular uptake and anticancer efficacy were significantly enhanced when cells were incubated with micelles at pH 6.5 due to the charge-reversal of micelles from negative to positive. With the protonation of Poly(DEA) moieties in acidic extracellular microenvironment and the pH-responsive DOX release with hydrazone linkage in endo/lysosome pH, this dual pH-responsive-charge-reversal micelle platform might become an encouraging strategy for more effective cancer treatment.

Delivery of RGD-modified liposome as a targeted colorectal carcinoma therapy and its autophagy mechanism.

Liposomes are among the most extensively applied drug carriers due to their excellent biocompatibility, controllable size and ease of modification. In the present study, we prepared untargeted liposomes (LP) and targeting liposomes modified with Arg-Gly-Asp (RGD-LP), and Doxorubicin Hydrochloride (DOX) or fluorescent probe was loaded. RGD-LP/DOX was identified to be uniformly spherical in size 131.2 ± 2.7 nm. Based on flow cytometry analysis and the confocal laser scanning microscopy, RGD-LP had a higher uptake into HRT-18 colorectal cancer cells than LP. Further, in vivo imaging study further suggested that RGD-LP could significantly increase the liposome accumulation in the tumour tissues of the mice bearing subcutaneous tumours. By investigating the targeting mechanism of RGD-LP, we found that they entered the cell via macropinocytosis. When loaded with DOX, RGD-LP exerted stronger tumour growth inhibitory activity against tumours of colorectal carcinoma compared to LP. Moreover, RGD-LP induced autophagy. Therefore, RGD-LP have the potential to be applied as a targeted colorectal carcinoma therapy.

Serum Metabonomics Reveals Risk Factors in Different Periods of Cerebral Infarction in Humans.

Studies of key metabolite variations and their biological mechanisms in cerebral infarction (CI) have increased our understanding of the pathophysiology of the disease. However, how metabolite variations in different periods of CI influence these biological processes and whether key metabolites from different periods may better predict disease progression are still unknown. We performed a systematic investigation using the metabonomics method. Various metabolites in different pathways were investigated by serum metabolic profiling of 143 patients diagnosed with CI and 59 healthy controls. Phe-Phe, carnitine C18:1, palmitic acid, cis-8,11,14-eicosatrienoic acid, palmitoleic acid, 1-linoleoyl-rac-glycerol, MAG 18:1, MAG 20:3, phosphoric acid, 5α-dihydrotestosterone, Ca, K, and GGT were the major components in the early period of CI. GCDCA, glycocholate, PC 36:5, LPC 18:2, and PA showed obvious changes in the intermediate time. In contrast, trans-vaccenic acid, linolenic acid, linoleic acid, all-cis-4,7,10,13,16-docosapentaenoic acid, arachidonic acid, DHA, FFA 18:1, FFA 18:2, FFA 18:3, FFA 20:4, FFA 22:6, PC 34:1, PC 36:3, PC 38:4, ALP, and Crea displayed changes in the later time. More importantly, we found that phenylalanine metabolism, medium-chain acylcarnitines, long-chain acylcarnitines, choline, DHEA, LPC 18:0, LPC 18:1, FFA 18:0, FFA 22:4, TG, ALB, IDBIL, and DBIL played vital roles in the development of different periods of CI. Increased phenylacetyl-L-glutamine was detected and may be a biomarker for CI. It was of great significance that we identified key metabolic pathways and risk metabolites in different periods of CI different from those previously reported. Specific data are detailed in the Conclusion section. In addition, we also explored metabolite differences of CI patients complicated with high blood glucose compared with healthy controls. Further work in this area may inform personalized treatment approaches in clinical practice for CI by experimentally elucidating the pathophysiological mechanisms.

Advances in kidney-targeted drug delivery systems.

The management and treatment of kidney diseases currently have caused a huge global burden. Although the application of nanotechnology for the therapy of kidney diseases is still at an early stages, it has profound potential of development. More and more nano-based drug delivery systems provide novel solutions for the treatment of kidney diseases. This article summarizes the physiological and anatomical properties of the kidney and the biological and physicochemical characters of drug delivery systems, which affects the ability of drug to target the kidney, and highlights the prospects, opportunities, and challenges of nanotechnology in the therapy of kidney diseases.

Kidney-targeted astaxanthin natural antioxidant nanosystem for diabetic nephropathy therapy.

Diabetic nephropathy (DN) is a frequent and severe microvascular complication associated with oxidative stress of diabetes mellitus. A novel astaxanthin-based natural antioxidant nanosystem, namely AST-GLU-LIP, with preferential renal uptake and bioavailability were prepared and applied for treatment of diabetic nephropathy in rats. Our results of kidney-targeted evaluation showed that glucose-PEG600-DSPE ligand modified AST liposomes could be specifically transported by overexpressed GLUT1 on the membrane of glomerular mesangial cells and achieved excellent kidney-targeted drug delivery. In addition, the results of pharmacodynamics and therapeutics in DN rats demonstrated that AST-GLU-LIP could improve the bioavailability and antioxidant capacity of AST to scavenge redundant ROS induced by oxidative stress. AST-GLU-LIP could also significantly improve the renal pathological morphology to protect the kidney as a therapeutic drug for diabetic nephropathy.