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Background/Objectives: In addition to oncological applications, poly(ADP-ribose) polymerase (PARP) inhibitors have potential as anti-inflammatory agents. Colon-targeted delivery of PARP inhibitors has been evaluated as a pharmaceutical strategy to enhance their safety and therapeutic efficacy against gut inflammation. Methods: Colon-targeted PARP inhibitors 5-aminoisoquinoline (5-AIQ) and 3-aminobenzamide (3-AB) were designed and synthesized by azo coupling with salicylic acid (SA), yielding 5-AIQ azo-linked with SA (AQSA) and 3-AB azo-linked with SA (ABSA). Additional conjugation of AQSA with acidic amino acids yielded glutamic acid-conjugated AQSA (AQSA-Glu) and aspartic acid-conjugated AQSA, which further increased the hydrophilicity of AQSA. Results: The distribution coefficients of PARP inhibitors were lowered by chemical modifications, which correlated well with drug permeability via the Caco-2 cell monolayer. All derivatives were effectively converted to their corresponding PARP inhibitors in the cecal contents. Compared with observations in the oral administration of PARP inhibitors, AQSA-Glu and ABSA resulted in the accumulation of much greater amounts of each PARP inhibitor in the cecum. ABSA accumulated mesalazine (5-ASA) in the cecum to a similar extent as sulfasalazine (SSZ), a colon-targeted 5-ASA prodrug. In the DNBS-induced rat colitis model, AQSA-Glu enhanced the anticolitic potency of 5-AIQ. Furthermore, ABSA was more effective against rat colitis than SSZ or AQSA-Glu, and the anticolitic effects of AQSA-Glu were augmented by combined treatment with a colon-targeted 5-ASA prodrug. In addition, the colon-targeted delivery of PARP inhibitors substantially reduced their systemic absorption. Conclusions: Colon-targeted PARP inhibitors may improve the therapeutic and toxicological properties of inhibitors and synergize the anticolitic effects of 5-ASA. [ABSTRACT FROM AUTHOR]

Background/Objectives: Owing to the growing resistance of methicillin-resistant Staphylococcus aureus (MRSA) to conventional antibiotics, the development of innovative therapeutic strategies for the treatment of MRSA-infected cutaneous wounds poses a significant challenge. Methods: Here, by using polyhydroxyalkanoates (PHA), emerging biodegradable and biocompatible polymers naturally produced by various microorganisms, we developed clindamycin-loaded PHA nanoparticles (Cly-PHA NPs) as a novel approach for the treatment of MRSA-infected cutaneous wounds. Results: Cly-PHA NPs were characterized in terms of mean particle size (216.2 ± 38.9 nm), polydispersity index (0.093 ± 0.03), zeta potential (11.3 ± 0.5 mV), and drug loading (6.76 ± 0.19%). Owing to the sustained release of clindamycin over 2 days provided by the PHA, Cly-PHA NPs exhibited potent antibacterial effects against MRSA. Furthermore, Cly-PHA NPs significantly facilitated wound healing in a mouse model of MRSA-infected full-thickness wounds by effectively eradicating MRSA from the wound bed. Conclusions: Therefore, our results suggest that Cly-PHA NPs offer a promising approach for combating MRSA infections and accelerating cutaneous wound healing. [ABSTRACT FROM AUTHOR]

Self-healing hydrogels have good mechanical strength, can endure greater external force, and have the ability to heal independently, resulting in a strong bond between the wound and the material. Bacterial biofilm infections are life-threatening. Clindamycin (Cly) can be produced in the form of a self-healing hydrogel preparation. It is noteworthy that the antibacterial self-healing hydrogels show great promise as a wound dressing for bacterial biofilm infection. In this study, we developed a polyvinyl alcohol/borax (PVA/B) self-healing hydrogel wound dressing that releases Cly. Four ratios of PVA, B, and Cly were used to make self-healing hydrogels: F1 (4%:0.8%:1%), F2 (4%:1.2%:1%), F3 (1.6%:1%), and F4 (4%:1.6%:0). The results showed that F4 had the best physicochemical properties, including a self-healing duration of 11.81 ± 0.34 min, swelling ratio of 85.99 ± 0.12%, pH value of 7.63 ± 0.32, and drug loading of 98.34 ± 11.47%. The B–O–C cross-linking between PVA and borax caused self-healing, according to FTIR spectra. The F4 formula had a more equal pore structure in the SEM image. The PVA/B-Cly self-healing hydrogel remained stable at 6 ± 2 °C for 28 days throughout the stability test. The Korsmeyer–Peppas model released Cly by Fickian diffusion. In biofilm-infected mouse wounds, PVA/B-Cly enhanced wound healing and re-epithelialization. Our results indicate that the PVA/B-Cly produced in this work has reliable physicochemical properties for biofilm-infected wound therapy. [ABSTRACT FROM AUTHOR]

Synthesis of benzo[a]fluorene, benzo[c]fluorene, and benzo[j]fluoranthene have been accomplished from readily accessible enol ether precursors via a Lewis acid‐catalyzed Prins‐type cycloaromatization. Mechanistically, it was proposed that Lewis acids catalyze the generation of oxonium species, which accelerate subsequent annulation and aromatization. This protocol offers the benefit of an operationally simple, transition‐metal‐free, and air‐tolerant reaction condition, enabling gram‐scale syntheses of the desired products. The total synthesis of viridistratin A further supported this synthetic strategy for establishing polycyclic aromatic hydrocarbon architectures. [ABSTRACT FROM AUTHOR]