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Milk exosomes (mExos) have demonstrated significant promise as vehicles for the oral administration of protein and peptide drugs owing to their superior capacity to traverse epithelial barriers. Nevertheless, certain challenges persist due to their intrinsic characteristics, including suboptimal drug loading efficiency, inadequate mucus penetration capability, and susceptibility to membrane protein loss. Herein, a hybrid vesicle with self-adaptive surface properties (mExos@DSPE-Hyd-PMPC) was designed by fusing functionalized liposomes with natural mExos, aiming to overcome the limitations associated with mExos and unlock their full potential in oral peptide delivery. The surface property transformation of mExos@DSPE-Hyd-PMPC was achieved by introducing a pH-sensitive hydrazone bond between the highly hydrophilic zwitterionic polymer and the phospholipids, utilizing the pH microenvironment on the jejunum surface. In comparison to natural mExos, hybrid vesicles exhibited a 2.4-fold enhancement in the encapsulation efficiency of the semaglutide (SET). The hydrophilic and neutrally charged surfaces of mExos@DSPE-Hyd-PMPC in the jejunal lumen exhibited improved preservation of membrane proteins and efficient traversal of the mucus barrier. Upon reaching the surface of jejunal epithelial cells, the highly retained membrane proteins and positively charged surfaces of the hybrid vesicle efficiently overcame the apical barrier, the intracellular transport barrier, and the basolateral exocytosis barrier. The self-adaptive surface properties of the hybrid vesicle resulted in an oral bioavailability of 8.7% and notably enhanced the pharmacological therapeutic effects. This study successfully addresses some limitations of natural mExos and holds promise for overcoming the sequential absorption barriers associated with the oral delivery of peptides.

Myelosuppression is a prevalent and potentially life-threatening side effect during chemotherapy. As the main active component of ginseng, 20( S )-protopanaxadiol (PPD) is capable of relieving myelosuppression by restoring hematopoiesis and immunity. In this study, PPD was encapsulated in human albumin nanoparticles (PPD-HSA NPs) by nanoparticle albumin-bound (Nab) technology for intramuscular injection to optimize its pharmacokinetic properties and promote recovery of myelosuppression. The prepared PPD-HSA NPs had a particle size of about 280 nm with a narrow size distribution. PPD dispersed as an amorphous state within the PPD-HSA NPs, and the NPs exhibited in vitro sustained release behavior. PPD-HSA NPs showed a favorable pharmacokinetic profile with high absolute bioavailability, probably due to the fact that NPs entered into the blood circulation via lymphatic circulation and were eliminated slowly. In vivo distribution experiments demonstrated that PPD-HSA NPs were mainly distributed in the liver and spleen, but a strong fluorescence signal was also found in the inguinal lymph node, indicating drug absorption via a lymph route. The myelosuppressive model was established using cyclophosphamide as the inducer. Pharmacodynamic studies confirmed that PPD-HSA NPs were effective in promoting the level of white blood cells. Moreover, the neutrophil and lymphocyte counts were significantly higher in the PPD-HSA NPs group compared with the control group. This preliminary investigation revealed that PPD-HSA NPs via intramuscular administration may be an effective intervention strategy to alleviate myelosuppression.

g-C 3 N 4 -assisted interface engineering has been developed as an effective method to improve the efficiency and stability of perovskite solar cells (PSCs). However, most of the reported works used g-C 3 N 4 -induced single-interface modification, which is difficult to passivate the bilateral interfaces of the perovskite layer at the same time. In this paper, we fabricated two kinds of C 3 N 4 materials simultaneously (w-CN and y-CN) after the twice calcination of melamine and used them in the bilateral interface modification toward all-inorganic PSCs. The two kinds of C 3 N 4 play different roles in different interface engineering. On the front interface, w-CN could optimize band level arrangement and improve the perovskite film quality, which contributes to the efficiency of the device. On the back interface, y-CN could also improve the film quality of the perovskite layer, accelerating the extraction of charge carriers. The champion efficiency of the CsPbIBr 2 -based device treated by the bilateral interface is significantly enhanced from 7.8 to 10.1%. Moreover, the modified perovskite film exhibits negligible degradation after 40 min of exposure in the ambient environment with a relative humidity of 70%, while the pristine perovskite film has a rapid degradation within 20 min.