Synthetic Studies of Zoaramine: Construction of the Tetracyclic Skeleton in High Oxidation State.

We report herein the synthetic studies toward zoaramine, a member of the family of zoaramine-type marine natural products bearing a unique structure. The major synthetic challenge is the stereoselective construction of the congested tetracyclic [6-6-6-6] skeleton in a high oxidation state. Our key strategies are the following: (1) radical cyclization was designed to install the quaternary stereocenters at C-9, C-22, and C-12 as well as formation of the B and D rings; (2) selective oxidations were realized to introduce the functional groups at C-11 and C-24 by using O/-BuOK-promoted hydroxylation and MeReO-catalyzed Rubottom oxidation.

Prolonged local retention of vancomycin achieved by a multivesicular liposomes in thermoresponsive gel system for the prevention and treatment of intervertebral disc infection.

The therapeutic efficacy of intervertebral disc (IVD) infections treated with intravenous vancomycin (VCM) is often limited by inadequate blood supply to the IVD. In this study, we developed a localized and sustained-release drug delivery system for the intradiscal administration of VCM. First, VCM-loaded multivesicular liposomes (VCM-MVLs) were prepared using a two-step emulsification process, and we investigated the effects of the preparation process and formulation composition on the quality of the MVLs.

pH-responsive ZIF-8 nanoplatform co-loaded with DSF and ICG for multiple synergistic antitumor therapy.

Disulfiram (Allensworth et al.), an "old drug" for the treatment of chronic alcohol dependence, has received extensive attention due to its potential antitumor activity for new medical applications. However, the application of DSF in cancer therapy was limited by its extremely terrible solubility in water.

Chitosan based surface modulation of core-shell nanoparticles for oral delivery of exenatide via balancing mucus penetration and cellular uptake.

Oral delivery of peptide and protein drugs (PDs) is hindered by the impermeable intestinal mucosa, which consists of both the mucus layer and the epithelium. Therefore, double-layer (mucus layer and epithelium) overcoming nanocarriers need to be designed to enhance the transporting efficiency of PDs. However, the requirements for surface properties to penetrate these two barriers are quite distinct.

Long-acting release of fluocinolone acetonide microspheres using electrospray technology for noninfectious uveitis therapy.

Intravitreous long-acting drug delivery system offers an excellent alternative to multiple injections for the treatment of noninfectious uveitis (NIU). However, the adverse effects of non-biodegradable intravitreal implants of fluocinolone acetonide (FA), such as postoperative hypotony and secondary injury during removal of the implant matrix, are frequent occurrence to affect patient's compliance. Herein, biodegradable poly (lactic-co-glycolic acid) (PLGA)-based microspheres (MS) containing fluocinolone acetonide (FA@MS) were prepared using an optimized electrospray technology with a voltage of 10.

Modulating the elasticity of milk exosome-based hybrid vesicles to optimize transepithelial transport and enhance oral peptide delivery.

To address challenges such as limited loading capacity, restricted targeting precision, and low yield of natural exosomes as drug carriers, the fusion of liposomes and exosomes to create hybrid vesicles has emerged as a viable solution approach. While current research mainly focuses on designing functionalized liposomes, less attention is given to how liposome membrane materials affect the elasticity of these hybrids and their delivery efficiency. This study utilized milk exosomes (mExos) as model exosomes, and generated hybrid vesicles with varying elasticity through the fusion of phospholipids with differing chain lengths, examining the disparities among various hybrid vesicles in their ability to overcoming the gastrointestinal barriers.

Characteristics of Tylvalosin Tartrate Enteric Amorphous Pellets Prepared by Liquid Layering.

Purpose: Tylvalosin Tartrate (TAT), a new-generation macrolide antibiotic, undergoes significant degradation in the stomach and in vivo rapid elimination upon oral administration, resulting in poor bioavailability. This study developed TAT enteric amorphous pellets by liquid layering (TAT/EAP-LL) with pH-sensitive and burst release characteristics, to enhance drug stability in the stomach and concentration enrichment in the duodenum.

Methods: The drug loading layer, isolation layer and enteric layer were formed on the surface of the blank core pellets.

Molecular mechanisms of nitric oxide regulating high photosynthetic performance of wheat plants in waterlogging at flowering.

Nitric oxide (NO) positively contributes to maintaining a high photosynthetic rate in waterlogged-wheat plants by maintaining high stomatal conductance (g), mesophyll conductance (g), and electron transport rates in PSII (J). However, the molecular mechanisms underlying the synergistic regulation of photosynthetic characteristics during wheat waterlogging remain unclear. Pot experiments were conducted with two cultivars: Yangmai15 (YM15: high waterlogging-tolerance capacity) and Yangmai24 (YM24: conventional waterlogging-tolerance capacity).

Valsartan Loaded Solid Self-Nanoemulsifying Delivery System to Enhance Oral Absorption and Bioavailability.

Valsartan (VST) is an angiotensin II receptor antagonist with low oral bioavailability. The present study developed a solid self-nanoemulsifying drug delivery system (S-SNEDDS) to enhance the oral absorption and bioavailability of VST. VST-loaded liquid SNEDDS (VST@L-SNEDDS) was prepared by investigating the solubility of VST and constructing the pseudo-ternary phase diagrams.

Lactoferrin-functionalized PEGylation liposomes loaded with norcantharidin acid for targeted therapy of hepatocellular carcinoma.

Norcantharidin (NCTD), an antitumor agent with an increased leukocyte function, has been used for the treatment of hepatocellular carcinoma (HCC) in clinical. However, the clinical application of NCTD is limited due to its inadequate hydrophilicity and lipophilicity, short half-life (t), as well as adverse effects such as vascular irritation, cardiotoxicity, and nephrotoxicity. Herein, a lactoferrin (Lf) and DSPE-mPEG functionalized liposomes loaded with norcantharidic acid (NCA), an active metabolite of NCTD, was constructed for the targeted therapy of HCC.

Enantioselective Excited-State Nazarov Reaction: A Relay Strategy of Electrocyclization and Parallel Kinetic Resolution.

We report herein the enantioselective photoinduced Nazarov reaction using a relay strategy of an electrocyclization, followed by parallel kinetic resolution (PKR). No enantioselectivity was observed during electrocyclization due to weak coordination between chiral ligands and the substrate's carbonyl group. However, PKR was successfully achieved in the deprotonation step with a bifunctional chiral thiourea ligand.

Catalyst-free and wavelength-tuned glycosylation based on excited-state intramolecular proton transfer.

The chemoselectivity of organic reactions is a fundamental topic in organic chemistry. In the long history of chemical synthesis, achieving chemoselectivity is mainly limited to thermodynamic conditions by an exogenous activation strategy. Here, we design an endogenous activation method, which can be used to control the chemoselectivity of phenol and naphthol through the photo-induced excited-state intramolecular proton transfer (ESIPT).

The journey of nanoparticles in the abdominal cavity: Exploring their in vivo fate and impact factors.

Peritoneal carcinomatosis (PC) is caused by metastasis of primary tumor cells from intra-abdominal organs to the peritoneal surface. Intraperitoneal (IP) chemotherapy allows close contact of high concentrations of therapeutic agents with cancer cells in the peritoneal cavity to prolong patient survival. However, conventional IP chemotherapy is prone to rapid elimination from the peritoneal cavity and lacks specificity towards cancer cells.

Asymmetric Photoinduced Excited-State Nazarov Reaction.

We report herein the first asymmetric photoinduced excited-state Nazarov reaction of non-aromatic dicyclic divinyl ketones by using hydrogen-bonding catalysis. The enantioselectivity of photoinduced electrocyclization is highly dependent on the structural features of the substrate and its interaction with chiral catalysts. For the simple dicyclic divinyl ketone substrates, there is no discernible selectivity of the hydrogen bond coordination between the thiourea and carbonyl groups of the substrates in the ground state.

Sodium glycocholate liposome encapsulated semaglutide increases oral bioavailability by promoting intestinal absorption.

The aim of this study was to prepare sodium glycocholate liposomes (SGC-Lip) encapsulating semaglutide (Sml) to improve oral bioavailability and better exert hypoglycemic effect. In this paper, SGC-Lip was prepared by reverse-phase evaporation method with particle size around 140 nm, potential around -27 mV, rounded morphology and better stability. The hypoglycemic and intestinal uptake effects of SGC-Lip and cholesterol-containing liposomes (CH-Lip) were comparatively investigated in rats, and the oral safety of SGC-Lip was examined by cytotoxicity assay.

Redox-sensitive disulfide-bridged self-assembled nanoparticles of dexamethasone with high drug loading for acute lung injury therapy.

Acute lung injury (ALI) arises from an excessive inflammatory response, usually progressing to acute respiratory distress syndrome (ARDS) if not promptly addressed. There is currently a limited array of effective treatments available for ALI. In this study, we developed disulfide bond-bridged prodrug self-assembled nanoparticles (referred to as DSSS NPs).

Milk Exosome-Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides.

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.

Glucocorticoids-based prodrug design: Current strategies and research progress.

Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract.

Research on the loading and release kinetics of the vincristine sulfate liposomes and its anti-breast cancer activity.

Vincristine (VCR), as a cytotoxic drug, is used clinically to treat acute lymphatic leukemia and breast cancer, and commonly used clinically as vincristine sulfate (VCRS). However, its clinical use is limited by unpredictable pharmacologic characteristics, a narrow therapeutic index, and neurotoxicity. The pH gradient method was used for active drug loading of VCRS, and the process route mainly includes the preparation of blank liposomes and drug-loaded liposomes.

Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

Purpose: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release.

Dual-Targeted Self-Adjuvant Heterocyclic Lipidoid@Polyester Hybrid Nanovaccines for Boosting Cancer Immunotherapy.

Tumor vaccines have demonstrated a modest response rate, primarily attributed to their inefficient delivery to dendritic cells (DCs), low cross-presentation, DC-intrinsic immunosuppressive signals, and an immunosuppressive tumor microenvironment (TME). Here, draining lymph node (DLN)-targeted and tumor-targeted nanovaccines were proposed to address these limitations, and heterocyclic lipidoid (A18) and polyester (BR647) were synthesized to achieve dual-targeted cancer immunotherapy. Meanwhile, oligo hyaluronic acid (HA) and DMG-PEG-Mannose were incorporated to prepare dual-targeted nanovaccines encapsulated with STAT3 siRNA and model antigens.

Development and in vitro/in vivo evaluation of famotidine hydrochloride bioadhesive sustained release suspension.

To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions to improve patient drug activities to achieve the expected therapeutic effect. The famotidine drug resin was prepared using the water bath method with carbomer 934 used as coating material. Microcapsules were prepared using the emulsified solvent coating method and appropriate excipients were used to prepare famotidine sustained release suspension.

Preparation and in vitro/in vivo evaluation of a pantoprazole sodium drug-resin liquid delayed release suspension.

A drug-resin liquid delayed-release suspension of pantoprazole sodium (PAZ-Na) was prepared to improve the effectiveness, convenience and safety of peptic ulcer treatment in children, the elderly and patients with dysphagia. Pantoprazole sodium drug-resin complexes (PAZ-Na-DRC) were prepared using the bath method. The fluidized bed coating method is used to coat it and then add excipients to make a dry suspension prepared before use.