The epidemic of multidrug-resistant gram-negative bacteria is an ever-growing global concern. Polymyxin B (PMB), a kind of “old fashioned” antibiotic, has been revived in clinical practice and mainly used as...

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need and phototheranostics is a promising approach due to its noninvasive treatment, negligible drug resistance, high spatial resolution imaging, and little side effect on normal tissues. [1][2][3][4][5][6] However, its development is hindered by the distinctive characteristics of GBM tumors. First, the penetration depth of the irradiating light should be sufficient to cross the barriers of the scalp, skull, and healthy brain tissues, which can severely attenuate light. [7][8][9][10] To tackle the light attenuation problem, near-infrared-II (NIR-II, 1000-1700 nm) absorbing photothermal agents (PTAs) are better options due to their deeper tissue penetration and minimized phototoxicity to healthy tissues compared to PTAs with NIR-I (700-1000 nm) absorption. [11][12][13][14][15] Second, PTAs need to be effectively delivered to the tumor tissue bypassing the blood-brain barrier (BBB) that prevents most macromolecules from entering the brain parenchyma and only allows essential nutrients and ions. [16][17][18][19] Third, an accurate imaging technique must be used to properly monitor the deep orthotopic brain tissue. Thus, the development of PTAs with strong NIR-II absorption, efficient BBB-crossing capability, and sensitive imaging properties is a remaining challenge and highly desired.Currently, most NIR-II PTAs research mainly focuses on organic molecules, including aggregation-induced emission dyes and conjugated polymers, [20][21][22][23] with respect to their good biocompatibility compared to the inorganic counterparts. Among organic materials, NIR-II-absorbing small organic molecules are still rare due to the deficiency of suitable building blocks. Perylenes, a class of commonly used small chromophore cores, have advantages in good photostability and high photothermal conversion efficiency (η), hence have been widely applied as NIR-I PTAs in photothermal therapy (PTT) and contrast agents in photoacoustic (PA) imaging. [24][25][26] However, to the best of our knowledge, perylene-derived PTAs with exceptional absorption in the NIR-II region have not been reported yet. The main design strategies endowing perylene-based PTAs with NIR-I absorption and high photothermal conversion efficiency include electron donor-acceptor (D-A) molecular Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near-infrared (NIR-II) bio-window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR-II-absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio-application after nano-encapsulation of N1 to function as a nano-agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor-acceptor unit and extending π-conjugation, the obtained N1 can absorb in 1000-1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline...

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Glycyrrhetinic acid (GA) is an anti-inflammatory drug with potential for development. However, the poor solubility of GA in water leads to extremely low bioavailability, which limits its clinical applications. Solid dispersions have become some of the most effective strategies for improving the solubility of poorly soluble drugs. Soluplus®, a non-cytotoxic amphiphilic solubilizer, significantly improves the solubility of BCS II drugs and improves the bioavailability of insoluble drugs. l-arginine (L-Arg) can be used as a small molecular weight excipient to assist in improving the solubility of insoluble drugs. In this study, we developed a new formulation for oral administration by reacting GA and L-Arg to form salts by co-solvent evaporation and then adding the polymer-solvent Soluplus® with an amphiphilic chemical structure to prepare a solid dispersion GA-SD. The chemical and physical properties of GA-SD were characterized by DLS, TEM, XRD, FT-IR and TG. The anti-inflammatory activity of GA-SD was verified by LPS stimulation of RAW 267.5 cells simulating a cellular inflammation model, TPA-induced ear edema model in mice, and ethanol-induced gastric ulcer model. The results showed that the amide bond and salt formation of GA-SD greatly improved GA solubility. GA-SD effectively improved the anti-inflammatory effect of free GA in vivo and in vitro, and GA-SD had no significant effect on liver and kidney function, no significant tissue toxicity, and good biosafety. In conclusion, GA-SD with L-Arg and Soluplus® is an effective method to improve the solubility and bioavailability of GA. As a safe and effective solid dispersion, it is a promising anti-inflammatory oral formulation and provides some references for other oral drug candidates with low bioavailability.