Comparison of a poloxamer-based thermally sensitive gel and an HPMC-based standard gel used to increase sildenafil citrate retention in the uterus.

Objective: Sildenafil citrate (SC) could promote uterine lining development, leading to successful embryo implantation. Due to the low oral bioavailability of the first-pass elimination of SC, it is necessary to develop a gel for vaginal administration to improve the efficacy.

Methods: A vaginal gel was prepared using the cold method to increase the retention of SC in the uterus, which allows for prolonged contact between SC and the vaginal mucosa.

Mupirocin-Piperine Microemulsion Hydrogels Accelerate Healing of Infected Wounds through Deep Penetration and Biofilm Disruption.

The emergence of bacteria resistant to multiple first-line antibiotics has created an urgent demand for effective alternatives and a comprehensive approach to the healing of infected wounds. This study developed synergistic microemulsion hydrogels (Mup-Pip-ME-gels) combining piperine's biofilm-disrupting properties with mupirocin's antibacterial activity to combat antibiotic resistance and enhance wound healing. The optimization of the formulation was carried out using a pseudoternary phase diagram and response surface methodology, resulting in a microemulsion with stable physical properties: an average particle size of 57.

Microneedle-mediated biomimetic nanoparticles for targeted antioxidant and anti-inflammatory therapy in age-related macular degeneration.

Age-related macular degeneration (AMD) remains the leading cause of vision loss worldwide, with the lack of effective treatment for dry AMD posing a significant clinical challenge. Current therapies for wet AMD, while effective, are invasive, costly, and associated with notable side effects. Dry AMD, which is characterized by progressive retinal damage driven by oxidative stress and inflammation, lacks targeted therapeutic options, underscoring the critical need for innovative intervention strategies.

Emodin nanocrystals enhanced mucus penetration and ameliorated bleomycin-induced pulmonary fibrosis by pulmonary delivery.

Pulmonary fibrosis (PF) is a progressive interstitial disease characterised by extracellular matrix deposition and destruction of lung tissue structure. Emodin (Emo) is a natural active compound with anti-inflammatory and antioxidant properties. The initiation of PF is prevented by reducing oxidative stress-induced damage to alveolar epithelial cells.

Polydopamine nanoparticles loaded with sodium ferulate for targeted therapy of myocardial infarction in endothelial cells.

Myocardial infarction (MI) is a leading cause of heart failure and death in cardiovascular diseases. Most drug trials currently fail due to inadequate local drug activity and side effects. In this study, we developed a novel polydopamine (PDA) nano delivery system that carries sodium ferulate (SF) and is modified with RGD peptides (SF/RGD-PDA NPs) for precise targeted delivery.

Bromocriptine mesylate-loaded nanoparticles co-modified with low molecular weight protamine and lactoferrin for enhanced nose-to-brain delivery in Parkinson's disease treatment.

Parkinson's disease confronts challenges in drug delivery due to the blood-brain barrier. Intranasal delivery bypasses the blood-brain barrier for improved drug bioavailability, yet narrow nasal space and brief retention time hinder clinical applicability. We conducted a Bromocriptine Mesylate-loaded PLGA nanoparticles co-modified with low molecular weight protamine (LMWP) and lactoferrin (Lf) (LMWP/Lf-BCM-NPs) for nose-to-brain delivery.

Distinct pathway activities are associated with prognosis and response to bortezomib-containing treatment in MCL1-M based molecular subtypes of multiple myeloma.

Multiple myeloma (MM) is the second most prevalent hematological malignancy and remains incurable with remarkable heterogeneity in prognosis and treatment response across the patients. Clinical diagnosis and the existing molecular classification systems are inadequate for predicting treatment responses. Based on the convergence between plasma cell development and MM pathogenesis, we identified a gene co-expression module centered on the plasma cell survival regulator MCL1 (MCL1 module, MCL1-M) in the transcriptomes of pre-treated MM, which enabled stratification of MM patients into MCL1-M high and MCL1-M low molecular subtypes with subtype-specific prognosis and response to bortezomib-containing treatment.

Resveratrol-loaded microemulsion based thermosensitive hydrogel for potential topical treatment of the vaginal inflammation.

Background: Vaginal inflammation is a prevalent gynecological condition. If left untreated, it can potentially spread to the urinary and reproductive systems.

Methods: In this study, we propose a resveratrol-loaded microemulsion-based thermosensitive hydrogel (Res-Me-Tsgel) and compare it with a chitosan hydrogel-based Res-Me-Cogel.

Precisional detection of lymph node metastasis using tFCM in colorectal cancer.

The detection of colorectal cancer (CRC) lymph node (LN) metastases significantly influences treatment choices, yet identifying them in samples is time-consuming and error-prone. To enhance efficiency, we have established a LN metastasis detection method utilizing triple-parameter flow cytometry (tFCM) and have conducted a comparative assessment of its accuracy and cost-effectiveness in contrast to conventional pathological examinations. This technique utilized biomarkers cytokeratin 20 (CK20), epithelial cell adhesion molecules (EpCAM), and Pan-CK.

The effect of NK cell therapy on sepsis secondary to lung cancer: A case report.

Patients with sepsis face high mortality rates and a bleak prognosis, prompting the need for advanced therapeutic interventions. A male patient diagnosed with moderately low-differentiated squamous cell carcinoma received diverse treatments, including radiotherapy, chemotherapy, immunotherapy, and targeted therapy to inhibit angiogenesis. Subsequently, he developed sepsis after comprehensive treatment, and conventional antibiotic combinations proved ineffective in combating the infection.

and evaluation of pulmonary administration of itraconazole nanostructured lipid carriers for pulmonary aspergillosis.

Objective: Pulmonary aspergillosis, which is a secondary complication of fungal pneumonia, is widely considered to have an increasing incidence and high mortality. Itraconazole (Itz) can inhibit ergosterol biosynthesis to treat pulmonary aspergillosis. Nevereless, Itz's clinical application is limited because of its poor water solubility, low oral bioavailability, and systemic hepatotoxicity.

Siglec-15 Is an Immune Suppressor and Potential Target for Immunotherapy in the Pre-Metastatic Lymph Node of Colorectal Cancer.

Lymph node metastasis indicates a poor prognosis in colorectal cancer. To better understand the underlying mechanisms of lymph node metastasis, we analyzed transcriptome characteristics of the pre-metastatic lymph node, a putative microenvironment favorable for the seeding and proliferation of cancer cells. Thus, we tried to compare and elucidate the transcriptional and immune characteristics of sentinel lymph nodes (SNs) with matched non-sentinel lymph nodes (NSNs) in colorectal cancer patients.

Immune Characters and Plasticity of the Sentinel Lymph Node in Colorectal Cancer Patients.

Purpose: This study is aimed at immunologically characterizing sentinel lymph nodes (SNs) in colorectal cancer (CRC) patients and identifying changes in immunological phenotype and function of SNs isolated from the tumor immunosuppressive microenvironment.

Methods: A total of 53 pairs of matched SNs and non-SNs (NSNs) were collected by using a lymph node tracer dye. Flow cytometry was performed to detect the immunophenotype of T cells as well as the expression of activation and inhibitory markers.

Ultra-small lipid carriers with adjustable release profiles for synergistic treatment of drug-resistant ovarian cancer.

Multidrug resistance has dramatically compromised the effectiveness of paclitaxel (PTX). The combined application of PTX and tetrandrine (TET) is a promising avenue in drug-resistant cancer therapy. However, poor drug release and limited intracellular drug accumulation greatly impede this combinational antitumor therapy.

MiR-181c sensitizes ovarian cancer cells to paclitaxel by targeting GRP78 through the PI3K/Akt pathway.

Primary cytoreductive surgery with platinum-taxane-based chemotherapy is the standard treatment for ovarian cancer (OC) patients; however, resistance to chemotherapy is a contributing factor to OC mortality. Paclitaxel (PTX), the most widely used taxane, has become the first-line drug against OC. The molecular mechanism of PTX resistance is different from that of platinum-based agents and is still not completely elucidated.

In vivo Pharmacokinetics and in vitro Release of Imatinib Mesylate-Loaded Liposomes for Pulmonary Delivery.

Background: Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of vascular endothelial and smooth muscle cells and causes occlusion of pulmonary arterioles that eventually results in right heart failure and death. The platelet-derived growth factor (PDGF) plays a prominent role in abnormal remodeling of pulmonary resistance vessels. Imatinib mesylate (IM), a PDGF-receptor tyrosine kinase inhibitor, was able to ameliorate PAH by reversing pulmonary vascular remodeling.

Integrated transcriptomic and proteomic analysis indicated that neurotoxicity of rats with chronic fluorosis may be in mechanism involved in the changed cholinergic pathway and oxidative stress.

Background: To reveal the underling molecular mechanism in brain damage induced by chronic fluorosis, the neurotoxicity and its correlation were investigated by transcriptomics and proteomics.

Methods: Sprague-Dawley rats were treated with fluoride at different concentrations (0, 5, 50 and 100 ppm, prepared by NaF) for 3 months. Spatial learning and memory were evaluated by Morris water maze test; neuronal morphological change in the hippocampus was observed using Nissl staining; and the level of oxidative stress including reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by biological methods.

DPPC-coated lipid nanoparticles as an inhalable carrier for accumulation of resveratrol in the pulmonary vasculature, a new strategy for pulmonary arterial hypertension treatment.

In this study, we investigated the feasibility of dipalmitoylphosphatidylcholine-coated lipid nanoparticles (DPPC-LNs) as a carrier for preferential accumulation into lungs of Resveratrol (Res), a potentially promising drug for the treatment of pulmonary arterial hypertension (PAH). Res-loaded DPPC-LNs were prepared following a thin film hydration-ultrasonic dispersion technique using glyceryl monostearate as lipid core. DPPC can reduce the interactions between nanoparticles and pulmonary surfactant.

In vitro Permeability and Bioavailability Enhancement of Curcumin by Nanoemulsion via Pulmonary Administration.

Background: Curcumin has shown considerable pharmacological activity, including antiinflammatory activity. Nevertheless, the pharmacological effect of curcumin may be limited because of poor water solubility, metabolizing rapidly and systemic elimination.

Objective: In the current research, a novel curcumin nanoemulsion (Cur-NE) was developed for improving in vitro permeability and bioavailability via pulmonary administration.

α-Tocopherol liposome loaded chitosan hydrogel to suppress oxidative stress injury in cardiomyocytes.

Myocardial infarction (MI) continues to be a major contributor to the morbidity and mortality across the globe. Injectable hydrogel, a tissue-engineered scaffold, recently demonstrated very promising in myocardial repair. However, the undesirable retention and survival of transplanted cells has limited their applications due to the oxidative stress microenvironment of MI lesions.

Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance .

Multidrug resistance (MDR) is a main clinical hurdle for chemotherapy of cancer, and overexpression of P-glycoprotein (P-gp) is a key factor. In the present study, a new co-delivery system for reversing MDR was designed and developed. The system was composed of curcumin (Cur) and piperine (Pip) encapsulated in solid lipid nanoparticles (SLNs) with tocopheryl polyethylene glycol succinate (TPGS) and Brij 78 [(Cur+Pip)-SLNs].

Nanoemulsion enhances α-tocopherol succinate bioavailability in rats.

The vitamin E analogue, α-tocopherol succinate (α-TOS), has a broad anti-tumor effect. α-TOS can induce cancer cells apoptosis and suppress tumor growth by targeting mitochondria. Low bioavailability of α-TOS is the major problem encountered with formulation development.

Novel murine tumour models depend on strain and route of inoculation.

This study describes variations in tumour growth patterns which occur when changes in the routes of inoculation and mouse strain are used to introduce tumours into established murine model systems that are known to vary in location and aggression. Intraperitoneal, subcutaneous, intravenous and hydrodynamic inoculations of B16F10 cells were compared among CD-1, C57BL/6 and Balb/c mice. Most surprisingly, allogeneic tumour growth in Balb/c mice after intravenous and hydrodynamic inoculation of B16F10 cells was faster than tumour growth in the syngeneic C57BL/6 mice.

Vitamin E derivative-based multifunctional nanoemulsions for overcoming multidrug resistance in cancer.

The multidrug resistance (MDR), including intrinsic and acquired multidrug resistance, is a major problem in tumor chemotherapy. Here, we proposed a strategy for modulating intrinsic and/or acquired multidrug resistance by altering the levels of Bax and Bcl-2 expression and inhibiting the transport function of P-gp, increasing the intracellular concentration of its substrate anticancer drugs. Vitamin E derivative-based nanoemulsions containing paclitaxel (MNEs-PTX) were fabricated in this study, and in vitro anticancer efficacy of the nanoemulsion system was evaluated in the paclitaxel-resistant human ovarian carcinoma cell line A2780/Taxol.

Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea.

Purpose: Supplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route.