Capsaicin Enhanced the Efficacy of Photodynamic Therapy Against Osteosarcoma via a Pro-Death Strategy by Inducing Ferroptosis and Alleviating Hypoxia.

Ferroptosis, a novel form of nonapoptotic cell death, can effectively enhance photodynamic therapy (PDT) performance by disrupting intracellular redox homeostasis and promoting apoptosis. However, the extremely hypoxic tumor microenvironment (TME) together with highly expressed hypoxia-inducible factor-1α (HIF-1α) presents a considerable challenge for clinical PDT against osteosarcoma (OS). Hence, an innovative nanoplatform that enhances antitumor PDT by inducing ferroptosis and alleviating hypoxia is fabricated. Capsaicin (CAP) is widely reported to specifically activate transient receptor potential vanilloid 1 (TRPV1) channel, trigger an increase in intracellular Ca2+ concentration, which is closely linked with ferroptosis, and participate in decreased oxygen consumption by inhibiting HIF-1α in tumor cells, potentiating PDT antitumor efficiency. Thus, CAP and the photosensitizer IR780 are coencapsulated into highly biocompatible human serum albumin (HSA) to construct a nanoplatform (CI@HSA NPs) for synergistic tumor treatment under near-infrared (NIR) irradiation. Furthermore, the potential underlying signaling pathways of the combination therapy are investigated. CI@HSA NPs achieve real-time dynamic distribution monitoring and exhibit excellent antitumor efficacy with superior biosafety in vivo. Overall, this work highlights a promising NIR imaging-guided "pro-death" strategy to overcome the limitations of PDT for OS by promoting ferroptosis and alleviating hypoxia, providing inspiration and support for future innovative tumor therapy approaches.

Dexamethasone Palmitate Encapsulated in Palmitic Acid Modified Human Serum Albumin Nanoparticles for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory joint condition characterized by symmetric, erosive synovitis leading to cartilage erosion and significant disability. Macrophages, pivotal in disease progression, release pro-inflammatory factors upon activation. We developed a nanoparticle delivery system (DXP-PSA NPs), based on palmitic acid modified human serum albumin (PSA), to deliver dexamethasone palmitate (DXP) directly to sites of inflammation, enhancing treatment effectiveness and minimizing possible side effects. The system actively targets scavenger receptor-A on activated macrophages, achieving selective accumulation at inflamed joints. In vitro effect and preliminary targeting abilities were investigated on LPS-activated RAW264.7 cells. The in vivo efficacy and safety were evaluated and compared side to side with commercially available lipid emulsion Limethason® in an advanced adjuvant-induced arthritis rat model. DXP-PSA NPs offer a novel approach to RA treatment and presents promising prospects for clinical translation.

The Advances in Phospholipids-Based Phase Separation Gels for the Sustained Release of Peptides, Proteins, and Chemotherapeutics.

Implantable drug delivery systems formed upon injection offer a host of advantages, including localized drug administration, sustained release, minimized side effects, and enhanced patient compliance. Among the various techniques utilized for the development of in situ forming drug implants, solvent-induced phase inversion emerges as a particularly promising approach. However, synthetic polymer-based implants have been associated with undesirable effects arising from polymer degradation. In response to this challenge, a novel category of drug delivery systems, known as phospholipids-based phase separation gels (PPSGs), has emerged. These gels, characterized by their low initial viscosity, exhibit injectability and undergo rapid transformation into in situ implants when exposed to an aqueous environment. A typical PPSG formulation comprises biodegradable components, such as phospholipids, pharmaceutical oil, and a minimal amount of ethanol. The minimized organic solvents in the composition show good biocompatibility. And the relatively simple composition holds promise for industrial-scale manufacturing. This comprehensive review provides an overview of the principles and advancements in PPSG systems, with specific emphasis on their suitability as drug delivery systems for a wide range of active pharmaceutical ingredients (APIs), spanning from small molecules to peptides and proteins. Additionally, we explore the critical parameters and underlying principles governing the formulation of PPSG-based drug delivery strategies, offering valuable insights on optimization strategies.

An in situ forming gel co-loaded with pirarubicin and celecoxib inhibits postoperative recurrence and metastasis of breast cancer.

Surgical removal combined with postoperative chemotherapy is still the mainstay of treatment for most solid tumors. Although chemotherapy reduces the risk of recurrence and metastasis after surgery, it may produce serious adverse effects and impair patient compliance. In situ drug delivery systems are promising tools for postoperative cancer treatment, improving drug delivery efficiency and reducing side effects. Herein, an injectable phospholipid-based in situ forming gel (IPG) was prepared for the co-delivery of antitumor agent pirarubicin (THP) and cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) in the surgical incision, and the latter are used extensively in adjuvant chemotherapy for cancer. After injection, the IPG co-loaded with THP and CXB (THP-CXB-IPG) underwent spontaneous phase transition and formed a drug reservoir that fitted the irregular surgical incisions perfectly. In vitro drug release studies and in vivo pharmacokinetic analysis had demonstrated the sustained release behaviors of THP-CXB-IPG. The in vivo therapeutic efficacy was evaluated in mice that had undergone surgical resection of breast cancer, and the THP-CXB-IPG showed considerable inhibition of residual tumor growth after surgery and reduced the incidence of pulmonary metastasis. Moreover, it reduced the systemic toxicity of chemotherapeutic agents. Therefore, THP-CXB-IPG can be a promising candidate for preventing postoperative recurrence and metastasis.

A new long-acting analgesic formulation for postoperative pain management.

Local anesthetics (LA), as part of multimodal analgesia, have garnered significant interest for their role in delaying the initiation of opioid therapy, reducing postoperative opioid usage, and mitigating both hospitalization duration and related expenses. Despite numerous endeavors to extend the duration of local anesthetic effects, achieving truly satisfactory long-acting analgesia remains elusive. Drawing upon prior investigations, vesicular phospholipid gels (VPGs) emerge as promising candidates for extended-release modalities in small-molecule drug delivery systems. Therefore, we tried to use the amphiphilicity of phospholipids to co-encapsulate levobupivacaine hydrochloride and meloxicam, two drugs with different hydrophilicity, to obtain a long-term synergistic analgesic effect. Initially, the physicochemical attributes of the formulation were characterized, followed by an examination of its in vitro release kinetics, substantiating the viability of extending the release duration of the dual drugs. Sequentially, in vivo investigations encompassing pharmacokinetic profiling and assessment of analgesic efficacy were undertaken, revealing a prolonged release duration of up to 120 h and attainment of optimal postoperative analgesia. Subsequently, inquiries into the mechanism underlying synergistic analgesic effects and safety evaluations pertinent to the delivery strategy were pursued. In summation, we successfully developed a promising formulation to achieve long-acting analgesia.

Dual-Targeting Macrophages and Hepatic Stellate Cells by Modified Albumin Nanoparticles for Liver Cirrhosis Treatment.

Hepatic cirrhosis has become a global public health concern with high mortality and currently lacks effective clinical treatment methods. Activation of hepatic stellate cells (HSCs) and the large number of macrophages infiltrating into the liver play a critical role in the development of liver cirrhosis. This study developed a novel modified nanoparticle system (SRF-CS-PSA NPs) in which Sorafenib (SRF) was encapsulated by palmitic acid-modified albumin (PSA) and further modified with chondroitin sulfate (CS). These modifications enabled the SRF-CS-PSA NPs to effectively target hepatic stellate cells (HSCs) and macrophages. SRF-CS-PSA NPs showed uniform particle size distribution of approximately 120 nm and high loading efficiency of up to 99.5% and can be taken up by HSCs and macrophages via CD44 and SR-A receptors, respectively. In a mouse model of liver cirrhosis, SRF-CS-PSA NPs demonstrated superior targeting and inhibition of HSCs and macrophages, effectively reversing the process of liver cirrhosis. Overall, our study demonstrates the potential of SRF-CS-PSA NPs as a targeted therapy for liver cirrhosis, with promising clinical applications.

Palmitic acid-modified human serum albumin paclitaxel nanoparticles targeting tumor and macrophages against breast cancer.

Breast cancer is the most common malignant tumor in women, and the liver is the main target organ for breast cancer metastasis. Once metastasis occurs, the prognosis is very poor. The uptake of PSA NPs made by our synthesized Palmitic acid-modified human serum albumin (PSA) in macrophages is about 15 times higher than that of HSA NPs. As a first-line chemotherapeutic drug, paclitaxel not only does not kill macrophages, but it can also polarize macrophages into classically activated macrophages (M1). We combined these two characteristics into PTX-PSA NPs, which achieved dual targeting of macrophages and tumor cells, improved the tumor microenvironment, and achieved a more effective anti-breast cancer drug effect than PTX-HSA NPs. On this basis, we also used the pathological characteristics of low vascular perfusion of breast cancer liver metastasis, and used the characteristics of macrophages that can release paclitaxel after internalizing paclitaxel, and use macrophages as the delivery system of breast cancer liver metastasis. Therefore,PTX-PSA NPs is better than PTX-HSA NPs to achieve anti-breast cancer liver metastasis.

Thinned-Young Apple Polyphenols Inhibit Halitosis-Related Bacteria Through Damage to the Cell Membrane.

The thinned young apple is a by-product and is generally discarded in the orchard during fruit thinning. The polyphenol content of thinned young apples is about 10 times more than that of ripe apples. In our study, the antibacterial effect of thinned young apple polyphenols (YAP) on the halitosis-related bacteria including Porphyromonas gingivalis, Prevotella intermedius, and Fusobacterium nucleatum was investigated. The minimum inhibitory concentrations of YAP against P. gingivalis, P. intermedia, and F. nucleatum were 8.0, 8.0, and 12.0 mg/ml, while the minimum bactericidal concentrations were 10.0, 10.0, and 14.0 mg/ml, respectively. The scanning electron microscopy and transmission electron microscopy analyses showed that after YAP treatment, the membrane surface of halitosis-related bacterial cells was coarse and the cell wall and membrane were separated and eventually ruptured. The integrity of the cell membrane was determined by flow cytometry, indicating that the cells with the integrity membrane significantly reduced as the YAP concentration treatment increased. The release of proteins and nucleic acids into the cell suspension significantly increased, and the membrane potential reduced after the YAP treatment. This research illustrated the antibacterial mechanism of YAP against halitosis-related bacteria and provided a scientific basis of utilizing the polyphenols from the discarded thinned young apples.

Effect of free amino acids and peptide hydrolysates from sunflower seed protein on the formation of pyrazines under different heating conditions.

Most research concerning pyrazine formation in the Maillard reaction is mainly focused on free amino acids (FAAs), but limited information is available on the effect of peptides and proteins. In this study, three Maillard model systems (i.e., glucose and native sunflower seed protein, hydrolyzed peptides or FAAs, respectively) were prepared, and their effect on the formation of volatiles were further compared at different heating conditions by using of headspace solid-phase microextraction equipped with gas chromatography/mass spectrometry (HS-SPME-GC/MS). It was found that pyrazines were the characteristic volatile compounds in tested Maillard models, and with increasing heating temperature and time, the varieties of pyrazine formation significantly increased. The optimum reaction condition for pyrazine formation was at 140 °C for 90 min, which was subsequently applied to all sets of Maillard models. Further analysis showed that the short chain peptides generated by hydrolyzing sunflower seed protein (SSP), especially the molecular weight ranging from 1.2 to 3.0 kDa, significantly promoted the formation of pyrazines, which highlights the important role of peptides in the Maillard reaction models and is expected to intensify aroma promotion in sunflower seed oil.