Pulmonary vascular endothelial cells (VECs) are the main damaged cells in the pathogenesis of various respiratory diseases and they mediate the development and regulation of the diseases. Effective intervention targeting pulmonary VECs is of great significance for the treatment of respiratory diseases. A variety of cell markers are expressed on the surface of VECs, some of which can be specifically combined with the drugs or carriers modified by corresponding ligands such as ICAM-1, PECAM-1, and P-selectin, to achieve effective delivery of drugs in lung tissues. In addition, the great endothelial surface area of the pulmonary vessels, the “first pass effect” of venous blood in lung tissues, and the high volume and relatively slow blood perfusion rate of pulmonary capillaries further promote the drug distribution in lung tissues. This review summarizes the representative markers at the onset of respiratory diseases, drug delivery systems designed to target these markers and their therapeutic effects.

Osteoporosis is a common bone disorder where the declined bone mass is far more than normal physiological status and usually associated with enhanced fracture risk, reduced bone strength and even deteriorated quality of life. Recent studies showed that statins could exert beneficial effects on bones via promoting osteoblastic activity mediated by increased expression of bone morphogenetic protein 2 and also by suppressing osteoclast proliferation. In this study, we developed atorvastatin-loaded tetracycline-poly (ethylene glycol)-poly(lactic-co-glycolic acid) (TC-PEG-PLGA/ATO) micelles for the targeted treatment of osteoporosis. The TC-PEG-PLGA was synthesized under the action of coupling reagents and then ATO was encapsulated through solvent diffusion method with encapsulation efficiency and drug loading of 89.32 ± 2.48% and 8.20 ± 0.53%, respectively. The release of ATO from micelles could be maintained for more than 48 h in pH 7.4 PBS. Pharmacokinetic results further demonstrated that TC-PEG-PLGA micelles could effectively shield ATO leakage from micelles and prolong their circulation time. Benefiting from TC specifically binding to hydroxyapatite (HAp), TC-PEG-PLGA/ATO micelles exerted good bone-targeted ability, as demonstrated by in vitro HAp affinity assay and biodistribution. Pharmacodynamic studies showed that TC-PEG-PLGA/ATO micelles could effectively improve bone mineral density and bone mechanical strength in osteoporotic rats. These results suggest that TC-PEG-PLGA/ATO micelles hold significant promise for the targeted treatment of osteoporosis.

Introduction: Sodium-dependent glucose transporter 2 (SGLT2) inhibitors are novel, potent oral anti-diabetic agents in a β-cell function-independent manner, inhibiting SGLT2-mediated renal glucose reabsorption and thus increasing urinary glucose excretion. Ertugliflozin (Steglatro^TM) is a new oral SGLT2 inhibitor for the treatment of patients with type 2 diabetes mellitus (T2DM) as a monotherapy or in combination with other anti-diabetic agents. Areas covered: This review summarizes the collected data concerning the pharmacokinetics, clinical efficacy, as well as safety and tolerability profiles of ertugliflozin given as a monotherapy for the management of T2DM. Expert opinion: Good glycemic control is crucial to the management of T2DM, and accordingly, anti-diabetic agents with various anti-hyperglycemic mechanisms are developed one after another. Based on the available clinical trials of ertugliflozin as a monotherapy for T2DM, it could be found that ertugliflozin effectively improves the glycemic control, body weight and blood pressure of patients with a low risk of hypoglycemia. It is also found that ertugliflozin moderately reduces their blood pressure, which is beneficial for decreasing the risk of cardiovascular disease. These attributes show the good potential of ertugliflozin as an adjunct treatment to diet and exercise for improving glycemic control in patients with T2DM.

A mitochondria-targeted dual-functional aggregation-induced emission luminogen, TPP-TPEDCH, was rationally designed and developed for intracellular mitochondrial imaging and photodynamic therapy. TPP-TPEDCH clearly showed the movements of mitochondria at various time points. Moreover, both in vitro and in vivo results demonstrated its excellent ROS generation ability and strong antitumor activity.

Background: Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood–brain barrier (BBB), resulting in the poor therapeutic outcomes. Results: In this study, the derivatization and dual targeted delivery technologies were used to actively transport antioxidant melatonin (MLT) into the mitochondria of oxidative stress-damaged cells in brain tissues. A mitochondrial targeting molecule triphenylphosphine (TPP) was conjugated to melatonin (TPP-MLT) to increase the distribution of melatonin in intracellular mitochondria with the push of mitochondrial transmembrane potential. Then, TPP-MLT was encapsulated in dual targeted micelles mediated by TGN peptide (TGNYKALHPHNG) with high affinity for BBB and SHp peptide (CLEVSRKNG) for the glutamate receptor of oxidative stress-damaged neural cells.TGN/SHp/TPP-MLT micelles could effectively scavenge the overproduced ROS to protect neuronal cells from oxidative stress injury during CIS occurrence, as reflected by the improved infarct volume and neurological deficit in CIS model animals. Conclusions: These promising results showed this stepwise-targeting drug-loaded micelles potentially represent a significant advancement in the precise treatment of CIS. Graphical