Preparation and in vivo and ex vivo studies of sirolimus nano-in-situ gel ophthalmic formulation.

Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system.

LncRNA nuclear-enriched abundant transcript 1 aggravates cerebral ischemia/reperfusion injury through activating early growth response-1/RNA binding motif protein 25 axis.

Ischemic stroke is a major global health issue. Ischemia and subsequent reperfusion results in stroke-related brain injury. Previous studies have demonstrated that nuclear-enriched abundant transcript 1 (NEATa and early growth response 1 (EGR1) are involved in ischemia reperfusion (IR) injury). In this study, we aimed to explore the roles of NEAT1/EGR1 axis as well as its downstream effector RNA binding motif protein 25 (RBM25) in cerebral IR injury. Oxygen-glucose deprivation/reperfusion (OGD/R) and middle cerebral artery occlusion (MCAO) were used to establish in vitro and in vivo models of cerebral IR injury, respectively. According to our data, NEAT1, EGR1, and RBM25 levels were elevated in OGD/R-exposed SK-N-SH and SH-SY5Y cells and cerebral cortex of MCAO mice. NEAT1, EGR1, or RBM25 knockdown effectively reduced infarct volumes and apoptosis, and improved neurological function. Mechanistically, NEAT1 directly interacted with EGR1, which restrained WW domain containing E3 ubiquitin protein ligase 1 (WWP1)-mediated ubiquitination of EGR1 and subsequently caused EGR1 accumulation. EGR1 bound to RBM25 promoter and transcriptionally activated RBM25. Rescue experiments indicated that RBM25 overexpression abolished the therapeutic effects of NEAT1 knockdown. In conclusion, this work identified a novel NEAT1/EGR1/RBM25 axis in potentiating brain injury after IR insults, suggesting a potential therapeutic target for ischemic stroke.

Investigation on Potential Biomarkers and Immune-Related Mechanisms of Ischemic Stroke.

BACKGROUND: This study aimed to reveal the detailed immune-related mechanisms underlying ischemic stroke (IS) and identify new immune-associated biomarkers for clinical management. METHODS: Differentially expressed genes (DEGs) between IS samples and normal controls were identified using the GSE16561 dataset. The feature genes of the immune cells were investigated using the GSE72642 dataset. Weighted correlation network analysis (WGCNA) was performed to reveal module genes, followed by an investigation of common DEGs and a functional enrichment analysis. Potential biomarkers were identified based on hub genes in protein-protein interaction networks and WGCNA. Finally, GSE158312 was used for biomarker verification. RESULTS: In total, 1230 DEGs were identified between the IS samples and normal controls. Seven clinically significant modules were identified using WGCNA. The yellow module genes were positively correlated with polymorphonuclear cells (PMNC), whereas the brown module genes were positively correlated with CD4+ T cells. Eight genes were selected as hub genes. These genes are mainly involved in functions such as the innate immune response. Upregulated TLR2 and ARG1 levels were significantly different between the two groups in the verification dataset. CONCLUSIONS: Our findings suggest ARG1 and TLR2 as novel biomarkers for IS. Upregulated TLR2 might play a role in IS development by participating in the innate immune response function.

LncRNA MEG3 suppresses PI3K/AKT/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF-α-treated keratinocytes and psoriatic mice.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disorder that causes patches of thick red skin and silvery scales and affects 1-3% of the population, which reduces patient's quality of life. Understanding the pathogenesis of psoriasis is crucial for developing novel therapeutic strategies. METHODS: HaCaT and NHEK cells were treated with TNF-α in vitro. A mouse model of psoriasis was established by topical imiquimod application on back skin. LncRNA MEG3 was cloned into the pcDNA3.1 vector and transfected in TNF-α-treated HaCaT and NHEK cells to overexpress its expression. Liposome-encapsulated pcDNA3.1-MEG3 was injected into imiquimod-treated mice via tail vein. RT-qPCR and western blot assays were used to examine the expression of lncRNA MEG3, IL-6, IL-8, IFN-γ, IL-1ß, LC3, Beclin 1, p62, p-p65, p65, NLRP3, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR respectively. The secretion of IL-6, IL-8, IFN-γ and IL-1ß was determined using ELISA assay. Immunofluorescence and immunohistochemistry methods were performed for analyzing the expression of LC3 and NLRP3 in cells and skin tissues respectively. LY294002 was used to block the PI3K/AKT/mTOR signalling. MTT assay was applied to test the toxicity of LY294002 to HaCaT and NHEK cells. RESULTS: LncRNA MEG3 expression levels were downregulated in TNF-α-treated HaCaT and NHEK cells and skin tissues of psoriatic mice model. TNF-α treatment enhanced inflammation and suppressed autophagy in HaCaT and NHEK cells, which were largely reversed by overexpression of lncRNA MEG3. Autophagy puncta and NLRP3 inflammasome assembly showed the same patterns with the expression of inflammation and autophagy markers in TNF-α-treated HaCaT and NHEK cells with or without lncRNA MEG3 overexpression. TNF-α-induced activation of the PI3K/AKT/mTOR signalling was abolished by lncRNA MEG3 overexpression in HaCaT and NHEK cells. Blocking the PI3K/AKT/mTOR signalling inhibited TNF-α-induced inflammation and restored autophagy level in TNF-α-treated HaCaT and NHEK cells. Overexpression of lncRNA MEG3 suppressed inflammation, promoted autophagy and inhibited the activation of the PI3K/AKT/mTOR signalling in a mouse model of psoriasis. CONCLUSION: LncRNA MEG3 facilitates autophagy and suppresses inflammation in TNF-α-treated keratinocytes and psoriatic mice, which is dependent on the PI3K/AKT/mTOR signalling pathway. Our study enhances the understanding of psoriasis and provides potential therapeutic targets for psoriasis.

Preparation, characterization, and anti-colon cancer activity of oridonin-loaded long-circulating liposomes.

In this study, oridonin-loaded long-circulating liposomes (LC-lipo@ORI) were prepared with the ethanol injection method. Its physicochemical properties and the morphology were characterized, and its stability and release profiles were evaluated. Furthermore, its antitumor effects were studied using two in vitro cell models of colon cancer and two tumor-bearing models in nude mice. The prepared LC-lipo@ORI was quasi-spherical, with a mean particle size of 109.55 ± 2.30 nm. The zeta potential was -1.38 ± 0.21 mV, the encapsulation efficiency was 85.79%±3.25%, and the drug loading was 5.87%±0.21%. In vitro release results showed that the cumulative release rate of LC-lipo@ORI at 12 h was 63.83%. However, ORI dispersion was almost completely released after 12 h. In vitro cytotoxicity results showed that, the inhibiting effects of LC-lipo@ORI on the proliferation of two types of colon cancer cells were apparently higher than those of ORI dispersion, whereas those of the blank carrier were not noticeable. In vivo studies confirmed that, the encapsulation of LC-lipo enhanced the inhibitory effects of ORI on tumor growth. These results indicated that LC-lipo@ORI a promising formulations for colon cancer treatment.

pH-sensitive chitosan-deoxycholic acid/alginate nanoparticles for oral insulin delivery.

Oral absorption of peptides/proteins is usually compromised by various gastrointestinal tract barriers. To improve delivery efficiency, chitosan-conjugated deoxycholic acid (CS-DCA) coupled with sodium alginate (ALG) was prepared to load insulin into pH-sensitive nanoparticles. The insulin-loaded chitosan-deoxycholic acid/alginate nanoparticles (CDA NPs) were characterized by size (143.3 ± 10.8 nm), zeta potential (19.5 ± 1.6 mV), entrapment efficiency (61.14 ± 1.67%), and insulin drug loading (3.36 ± 0.09%). The CDA NPs exhibited pH-triggered release characteristics in vitro and protected the wrapped insulin from gastric degradation. Stability of the CDA NPs in enzyme-containing simulated gastrointestinal fluids suggested that the NPs could partially protect the wrapped insulin from enzymatic degradation. Additionally, CS-DCA-modified NPs promoted the permeability of Caco-2 cells and enhanced intracellular absorption of FITC-labeled insulin by 9.4 and 1.2-folds, when compared to insulin solution and unmodified NPs, respectively. The positively charged NPs increased intestinal villi adhesion and enhanced insulin absorption in the intestines of diabetic rat models. Furthermore, the hypoglycemic test showed that CDA NPs prolonged insulin release in vivo and exerted a remarkable hypoglycemic effect on diabetic rats with an oral bioavailability of 15%. In conclusion, CDA NPs is a potential oral insulin delivery system.

Pharmacokinetic Study of Ferulic Acid Following Transdermal or Intragastric Administration in Rats.

Ferulic acid is contained in some Chinese herbal medicines such as Ligusticum chuanxiong or Angelica sinensis. Studies have focused on the treatment of inflammatory diseases and pain using ferulic acid. However, little is known about its pharmacokinetics after transdermal administration. The present research investigated the pharmacokinetic behavior of ferulic acid in rat plasma and skin microdialysate after ferulic acid transdermal or intragastric administration. Samples collected at predetermined time points were determined by a simple and sensitive HPLC-UV method. The pharmacokinetic parameters were estimated using non-compartmental analysis with DAS 2.0 software. The values of AUC0-t and Cmax after intragastric administration (20 mg/kg) in plasma were 281.47 ± 46.76 min mg/L and 12.20 ± 2.46 mg/L, respectively. After emulsion transdermal administration (117 mg/kg, 35 mg/4 cm2), the values of AUC0-t and Cmax in plasma and skin microdialysate were 953.90 ± 175.30 min mg/L, 7630.47 ± 1410.33 min mg/L, 3.00 ± 0.61 mg/L, and 19.08 ± 4.39 mg/L, respectively. Here, we show a promising delivery system for ferulic acid that could replace traditional administration, and a better understanding of the transdermal pharmacokinetics of ferulic acid, which may be helpful for further clinical and laboratory studies.

Hypothermia alleviated LPS-induced acute lung injury in Rat models through TLR2/MyD88 pathway.

Acute lung injury (ALI) is a common clinical syndrome in ICU departments with high mortality. The pathology of ALI is still not clear and there is no specific and efficient treatment against ALI. In this study, we established ALI rat model through lipopolysaccharide administration. We found that hypothermia therapy led to significant improvement in oxygenation index, edema formation and pathological score, demonstrating that hypothermia is beneficial to the recovery of lung function and alleviation of lung injury. Besides, hypothermia resulted in a decrease in plasminogen activator inhibitor-1(PAI-1) concentration, showing the inflammation was partially inhibited. This was also confirmed by a decrease in TNF-α mRNA and protein level in hypothermia group. The effect of hypothermia was mediated by TLR2/MyD88 signaling, which led to the alteration in NF-κB p65 level. Collectively, this study indicated that hypothermia therapy was potentially an efficient therapy against ALI.

Genome-wide gene expression profiling of tongue squamous cell carcinoma by RNA-seq.

OBJECTIVE: Tongue squamous cell carcinoma (TSCC) is significantly more malignant than other type of oral squamous cell carcinoma (OSCC). In this study, we aimed to identify specific global gene expression signatures of TSCC to investigate the more invasive behavior of the deeply infiltrating cancer. METHODS: Using RNA-seq technology, we detected gene expression of 20 TSCCs, 20 matched paratumor tissues, and 10 healthy normal mucosa tissues. Enrichment analysis of gene ontology (GO) and pathway was conducted using online tools DAVID for the dysregulated genes. Additionally, we performed the quantitative real-time RT-PCR (qRT-PCR) to validate the findings of RNA-Seq in 10 samples of TSCC, matched paratumor, and normal mucosa, respectively. RESULTS: We detected 252 differentially expressed genes (DEGs) between TSCC and matched paratumor tissue, including 117 up-regulated and 135 down-regulated genes. For comparison between TSCC and normal mucosa, 234 DEGS were identified, consisting of 67 up-regulated and 167 down-regulated genes. For both two comparisons, GO categories of muscle contraction (GO: 0006936), epidermis development (GO: 0008544), epithelial cell differentiation (GO: 0030855), and keratinization (GO: 0031424) were commonly enriched. Altered gene expression affected some cancer-related pathways, such as tight junction. The qRT-PCR validation showed that gene expression patterns of FOLR1, NKX3-1, TFF3, PIGR, NEFL, MMP13, and HMGA2 were fully in concordance with RNA-Seq results. CONCLUSION: Findings in this study demonstrated the genetic and molecular alterations associated with TSCC, providing new clues for understanding the molecular mechanisms of TSCC pathogenesis.

Liver, blood microdialysate and plasma pharmacokinetics of matrine following transdermal or intravenous administration.

Matrine is contained in several herbs used in traditional Chinese medicine, named Sophora alopecuroides, Sophora flavescens or Sophora subprostrata. In vitro and in vivo studies have focused on the treatment of chronic hepatitis or liver fibrosis using matrine. However, little is known about its liver pharmacokinetic profile. In this study pharmacokinetics of matrine in rat organs and tissues, such as liver, blood and skin were studied after intravenous (40 mg/kg) or transdermal administration (6 mg/cm2, 5 cm2). Samples were collected at timed intervals for measurement of matrine by a HPLC-UV method. The pharmacokinetic parameters were calculated by non-compartmental analysis using DAS 2.0. The AUC(0-t) values in the liver, blood microdialysates and plasma after intravenous administration were 395.91±74.48, 848.86±146.35 and 1304.07±305.92 min·mg/l, respectively. Following transdermal administration, the AUC(0-t) value in the liver, blood, plasma and skin microdialysates were 695.30±233.79, 1096.07±390.71, 2767.57±518.48 and 42735.77±27938.33 min·mg/l, respectively. Here, we show a promising delivery system for matrine that could replace traditional administration, and a better understanding of the transdermal pharmacokinetics of matrine, which may be helpful for further clinical and laboratory studies.

The anterolateral thigh flap for soft tissue reconstruction in patients with tongue squamous cell carcinoma.

BACKGROUND: Surgery remains the first choice of treatment for tongue cancer. Immediate reconstruction should be performed after wide resection of tumour. The aim of this study was to evaluate the anterolateral thigh flap for reconstruction of lingual defects. METHODS: We report 39 consecutive oral tongue squamous cell carcinoma patients who underwent lingual reconstruction with the anterolateral thigh flap between 2009 and 2010. RESULTS: The width of the skin island was 4 to 5 cm and the length of the skin island was 6 to 8 cm in 31 patients with T2 tumour, while the width of the skin island was 5.5 to 6 cm and the length of the skin island was 9 to 12 cm in 8 patients with T3/4 tumours. The all flap survival rate was 97.5 % in our series. CONCLUSIONS: We could obtain sufficient flap volume using the anterolateral thigh flap for tongue reconstruction. The single perforator-based anterolateral thigh flap is a good option for soft tissue reconstruction in patients with oral tongue squamous cell carcinoma.

The impact of clinical prognostic factors on the survival of patients with oral squamous cell carcinoma.

PURPOSE: This study investigated prognostic factors and useful predictors for survival in patients with oral squamous cell carcinoma. PATIENTS AND METHODS: The medical records of all patients with oral squamous cell carcinoma who underwent curative surgery with or without adjuvant radiation from 2009 through 2011 were retrospectively reviewed. RESULTS: Seventy-seven patients (63 men and 14 women) were enrolled. The 2-year disease-free and overall survival rates were 67.5% and 74%, respectively. Multivariate analyses showed that a diagnostic delay longer than 2 months (hazard ratio [HR]=4.43; 95% confidence interval [CI], 1.26-15.51; P=.02), T3 or T4 tumor (HR=4.40; 95% CI, 1.91-10.12; P=.001), neck metastasis (HR=1.96; 95% CI, 1.21-4.37; P=.01), and stage III or IV disease (HR=3.94; 95% CI, 1.64-9.47; P=.002) were independent adverse factors for survival rate. CONCLUSION: Oral squamous cell carcinoma is an important health issue associated with poor survival. A diagnostic delay longer than 2 months, T3 or T4 tumor, neck metastasis, and stage III or IV disease were independent adverse factors for subsequent survival rate and locoregional recurrence in patients with oral squamous cell carcinoma.

Effect of mild hypothermia on the expression of toll-like receptor 2 in lung tissues with experimental acute lung injury.

OBJECTIVE AND DESIGN: Our study aimed to determine the effect of mild hypothermia (MHT) on the expression of toll-like receptor 2 (TLR2) in lung tissue with acute lung injury. The animals were randomly divided into control, model and mild hypothermia groups. METHODS: A total of 40 rats was used in the study. Acute lung injury was induced by lipopolysaccharide and MHT was maintained at 32.5∼33.0 °C using body surface ice-bag placement combined with animal thermostat system. The ratio of PaO2/FiO2 was recorded. The mRNA and protein expressions of TLR2 were measured by real-time polymerase chain reaction and western blotting respectively. Moreover, enzyme linked immunosorbent assay were used for the quantification of TNF-α. RESULTS: The ratio of PaO2/FiO2 was increased by MHT. TLR2 and TNF-α were increased in the rat lung 1h and 8h in the rats with acute lung injury while they were significantly decreased by MHT. Histological examination revealed that MHT alleviated the degree of inflammation. CONCLUSION: Our study suggested that MHT might improve the lung function by inhibiting the inflammation via down-regulating the expressions of TLR2 in the acute injury lung tissues.

Brain microdialysate, CSF and plasma pharmacokinetics of ligustrazine hydrochloride in rats after intranasal and intravenous administration.

The aim of this work was to investigate the pharmacokinetics of ligustrazine hydrochloride (LZH) in plasma, cerebrospinal fluid (CSF) and cerebral cortex after intranasal (10 mg/kg) or intravenous administration (10 mg/kg) in male Sprague-Dawley rats. Plasma, CSF and cerebral cortex microdialysates were collected at timed intervals for the measurement of LZH by a quick and sensitive HPLC-UV method. LZH entered the brain quickly following both routes of administration. No significant difference was observed between the AUCCSF or cortex /AUCplasma ratio of LZH after intranasal administration (38.4%, 17.4%) and that after intravenous injection (45.9%, 19.9%). The drug targeting index (DTI) was 0.85 and 0.91 in the CSF and cortex, respectively. In conclusion, LZH is rapidly absorbed into the systemic circulation following intranasal administration. There is no direct pathway for LZH transport from the nasal cavity to the brain. The rapidity and magnitude of LZH penetration into the brain indicate that intranasal administration of this agent is a promising alternative to intravenous administration.

[Preparation and in vitro permeation of tetramethylpyrazine hydrochloride transdermal gel].

The purpose of this study was to prepare tetramethylpyrazine hydrochloride transdermal gel and to study its permeation ability in vitro. The skin permeation ability was evaluated by Valian-Chien permeation cells with isolated rat skin. The concentration of tetramethylpyrazine in samples was determined by HPLC. The optimal formulation was composed with 5% azone, 5% peppermint oil, 8% sodium carboxymethylcellulose and 8% tetramethylpyrazine hydrochloride. The accumulative permeation amount of the gel was (6 731.87 +/- 102.31) microg x cm(-2) in 12 h,and the permeation rate was (535.02 +/- 33.89) microg x cm(-2) x h(-1). The release profile in vitro was in line with zero-order formulation. Tetramethylpyrazine hydrochloride gel prepared in the study would be developed as a novel transdermal preparation.

Research progress of ophthalmic preparations of immunosuppressants.

Immune ophthalmopathy is a collection of autoimmune eye diseases. Immunosuppressants are drugs that can inhibit the body's immune response. Considering drug side effects such as hepatorenal toxicity and the unique structure of the eye, incorporating immunosuppressants into ophthalmic nanodrug delivery systems, such as microparticles, nanoparticles, liposomes, micelles, implants, and in situ gels, has the advantages of improving solubility, increasing bioavailability, high eye-target specificity, and reducing side effects. This study reviews recent research and applications of this aspect to provide a reference for the development of an ophthalmic drug delivery system.

Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery.

Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The objective of this study was to formulate an ophthalmic ion-sensitive in situ gel (ISG) of BRT to increase the retention time of the drug and its bioavailability. The optimum formulation of 2 mg/mL BRT-ISG was obtained with 0.45% gellan gum as the gel matrix. In vitro release results showed that the water-soluble drug bromonidine tartrate in ocular in situ gels exhibited a high burst effect and fast release in solution. The results of dialysis membrane permeation showed that there was a significant difference between the commercially available and BRT-ISG groups after 45 min. The results of the pre-corneal retention study indicated that gellan gum can effectively prolong ocular surface retention. Preliminary stability results showed that it should be stored in a cool and dark place, and the formulation under long-term preservation can be basically stable. The pharmacokinetic study of the BRT-ISG in the anterior chamber of the rabbit eye was studied by microdialysis technique, and microdialysis samples were analyzed by LC-MS/MS. The pharmacokinetic study showed that the BRT-ISG reached Cmax (8.16 mg/L) at 93 min after administration, which was 2.7 times that of the BRT eye drops, and the AUC(0-t) (1397.08 mg·min/L) was 3.4 times that of the BRT eye drops. The optimal prescription can prolong the retention time of BRT in front of the cornea and significantly improve the bioavailability of BRT in the eye. Combined with the results of in vitro release, permeation and pre-corneal retention studies, the improvement of BRT-ISG bioavailability in rabbit eyes was found to be mainly due to the retention effect after the mixture of ISG and tears.

A study on puerarin in situ gel eye drops: Formulation optimization and pharmacokinetics on rabbits by microdialysis.

Puerarin (PUE), an isoflavonoid isolated from Pueraria lobata (Willd) Ohwi root, is a ß-adrenergic receptor inhibitor used in treating glaucoma. The concentration range of gellan gum was determined based on the formulation viscosity and gelling capacity. PVP-K30 and gellan gum were used as variables, with the viscosity of formulation: STF = 40: 21, the 4 h permeation rate of rabbit isolated sclera, and 2 h in vitro release rate as response values. The JMP software was used to optimize the results, presenting that gellan gum was the main factor influencing viscosity. The in vitro release and permeation rate were primarily influenced by PVP-K30. The optimal prescription was 0.45% gellan gum and 6.0% PVP-K30. The in vitro release and permeation characteristics of puerarin in situ gel (PUE-ISG) were investigated using PUE solution as a control. The dialysis bag method results indicated that the release of the solution group leveled off after 4 h, while the PUE-ISG group had been continuously releasing. However, the cumulative release rates of the two were no longer significantly different at 10 h. The cumulative permeation rates of the ISG and solution groups were not significantly different (P > 0.05) in the rabbit isolated sclera. The apparent permeability Papp and steady-state flux Jss of PUE-ISG were 0.950 ± 0.059 cm/h and 9.504 ± 0.587 mg·(cm·h), respectively. A sensitive and stable HPLC-MS/MS analytical method for quantifying aqueous humor concentrations of PUE was validated. A microdialysis technique was successfully used in the aqueous humor pharmacokinetics study to sample aqueous humor from rabbit eye continuously. The results revealed that PUE-ISG significantly increased the drug concentration in the aqueous humor, with Cmax and AUC(0-t) 3.77 and 4.40 times higher than those of the solution group, respectively. Tmax was also significantly prolonged, indicating good prospects for clinical application. The developed PUE-ISG preparation has the characteristics of rapid drug release and sustained permeation, and increase the drug concentration in aqueous humor, with all inactive ingredients remaining within the maximum allowable limits recommended by the FDA guideline.

Precise nanodrug delivery systems with cell-specific targeting for ALI/ARDS treatment.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common acute and critical diseases in clinics and have no effective treatment to date. With the concept of "precision medicine", research into the precise drug delivery of therapeutic and diagnostic drugs has become a frontier in nanomedicine research and has entered the era of design of precise nanodrug delivery systems (NDDSs) with cell-specific targeting. Owing to the distinctive characteristics of ALI/ARDS, designing NDDSs for specific focal sites is an important strategy for changing drug distribution in the body and specifically increasing drug concentration at target sites while decreasing drug concentration at non-target sites. This strategy enhances drug efficacy, reduces adverse reactions, and ensures accurate nano-targeted treatment. On the basis of the characteristics of pathological ALI/ARDS microenvironments, this paper reviews NDDSs targeting vascular endothelial cells, neutrophils, alveolar macrophages, and alveolar epithelial cells to provide reference for designing accurate NDDSs for ALI/ARDS and novel insights into targeted treatments for ALI/ARDS.