A study on the treatment of rheumatoid arthritis with lipid nanoparticles containing mRNA encoding heat shock protein 10.

In order to delay the progression of Rheumatoid Arthritis (RA) in patients, and to prevent further teratogenesis and irreversible bone erosion through drug intervention in the early stages of inflammation, this experiment used the mRNA encoding heat shock protein 10 (HSP10) (H-mRNA) as the main therapeutic drug and used Microfluidics technology to prepare lipid nanoparticles (LNP) (H-mRNA LNPs) containing H-mRNA, and the surface of H-mRNA-LNPs was modified using heparin particals to obtain the final formulation H-mRNA-LNPs @ heparin/ Protamine. Through the sequence modification and effect evaluation of H-mRNA, we explored the formulation screening, physical characterization, cytotoxicity in vitro, distribution in vivo, pharmacodynamics in vivo, and safety in vivo of the prepared lipid nanoparticles, which proved that this nano-preparation had good anti Rheumatoid Arthritis effects, and conducted a preliminary exploration for the application of nucleic acid drugs in the treatment of diseases outside of tumors. This research would provide new ideas for the treatment of RA.

Preparation and release pattern study of long-term controlled release Blonanserin microspheres.

To prepare a PLGA microsphere loaded with the antipsychotic Blonanserin without release leg period and released in a near-zero model for long time, in this study, 15 kDa and 75 kDa PLGA were chosen to be mixed with different ratios, and Blonanserin microspheres (Bn-MS) without significant differences in the particle size, drug loading capacity, and encapsulation rate were prepared by microfluidics. The release kinetic model was fitted to the release behavior by monitoring the changes in particle size and morphology during the Bn-MS release to investigate microspheres' in vitro release pattern. The results showed that the addition of appropriate ratios of mixed molecular weights to Bn-MS could eliminate the release hysteresis period.

Multifunctional injectable microspheres for osteoarthritis therapy via spatiotemporally modulating macrophage polarization and inflammation.

Local injection of anti-inflammatory drugs for osteoarthritis emerged as a promising administration in the clinic, and sustained-release dosage forms have great potential for future therapeutic applications. Controlling the response of patients only in the acute inflammatory phase is currently the focus of therapeutic interventions. To relieve acute pain in patients and to improve the long-term prognosis effect of osteoarthritis treatment, we designed a two-pronged approach in this research: an injectable double-layer microsphere containing a "nonsteroidal anti-inflammatory drug - macrophage polarizing factor" was constructed.

Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application.

Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.

Advancements in gradient bone scaffolds: enhancing bone regeneration in the treatment of various bone disorders.

Bone scaffolds are widely employed for treating various bone disorders, including defects, fractures, and accidents. Gradient bone scaffolds present a promising approach by incorporating gradients in shape, porosity, density, and other properties, mimicking the natural human body structure. This design offers several advantages over traditional scaffolds.

[A comparative study of raw Aurantii Fructus Immaturus and bran-fried products on dryness of rats with slow-transit constipation].

The differences in dryness between raw Aurantii Fructus Immaturus(AFI) and bran-fried products were investigated based on a slow-transit constipation(STC) model. Seventy healthy SPF-grade rats were randomly divided into a blank group(K), a positive drug group(Y), a model group(M), low-and high-dose raw AFI groups(SD and SG), and low-and high-dose bran-fried AFI groups(FD and FG). During the experiment, it was found that compared with the K group, the groups with drug treatment had little effect on the daily body weight of the STC rats.

Design of in vitro biomimetic experimental system and simulation analysis for transvascular transport of nano-preparation.

Recently, the enhanced penetration and retention (EPR) effect of nano-preparations has been questioned. Whether the vascular endothelial cell gap (VECG) is the main transport pathway of nano-preparations has become a hot issue at present. Therefore, we propose an in vitro biomimetic experimental system that demonstrates the transvascular transport of nano-preparation.

Relaxin-Loaded Inhaled Porous Microspheres Inhibit Idiopathic Pulmonary Fibrosis and Improve Pulmonary Function Post-Bleomycin Challenges.

Idiopathic pulmonary fibrosis (IPF) causes worsening pulmonary function, and no effective treatment for the disease etiology is available now. Recombinant Human Relaxin-2 (RLX), a peptide agent with anti-remodeling and anti-fibrotic effects, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, due to its short circulating half-life, optimal efficacy requires continuous infusion or repeated injections.

Advances in Mechanical Properties of Hydrogels for Cartilage Tissue Defect Repair.

Numerous factors, such as degeneration and accidents, frequently cause cartilage deterioration. Owing to the absence of blood vessels and nerves in cartilage tissue, the ability of cartilage tissue to heal itself after an injury is relatively low. Hydrogels are beneficial for cartilage tissue engineering owing to their cartilage-like structure and advantageous properties.

Novel coatings for the continuous repair of human bone defects.

Bone defects are the second most common tissue grafts after blood. However, bone grafts face several problems, such as bone scaffolds, which have low bioactivity and are prone to corrosion. Much of the current research on bone scaffolds is focused on the mechanical aspects such as structure and strength.

Bioinspired Nanocomplexes Comprising Phenolic Acid Derivative and Human Serum Albumin for Cancer Therapy.

Inspired by the natural phenomenon of phenolic-protein interactions, we translate this "naturally evolved interaction" to a "phenolic acid derivative based albumin bound" technology, through the synthesis of phenolic acid derivatives comprising a therapeutic cargo linked to a phenolic motif. Phenolic acid derivatives can bind to albumin and form nanocomplexes after microfluidic mixing. This strategy has been successfully applied to different types of anticancer drugs, including taxanes, anthraquinones, etoposides, and terpenoids.

Molecular dynamics simulation of hyaluronic acid hydrogels: Effect of water content on mechanical and tribological properties.

Background And Objective: Recently conducted biomedical studies have shown that the drug diffusivity of hyaluronic acid hydrogel plays an important role in the treatment of joint diseases. The drug diffusivity is closely related to the water content of hydrogel. In addition, different water content will not only affect its mechanical and tribological properties, but also change the effect of drug release.

Nanobubbles loaded with carbon quantum dots for ultrasonic fluorescence dual detection.

To increase the efficiency and accuracy of clinical tumor detection, we explored multiple imaging by preparing carbon quantum dot (CQD)-loaded nanobubbles for ultrasonic fluorescence dual detection. In this experiment, we prepared 1,2-dioleoyl3-trimethylammonium-propane chloride (DOTAP) cationic liposomes using the film dispersion method and chose perfluoropentane as the core gas material of the nanobubbles. The nanobubbles were coupled with the negatively charged CQDs through the charge effect to prepare the testing agent for two-way diagnosis with ultrasound contrast and fluorescence detection.

CFD simulation of porous microsphere particles in the airways of pulmonary fibrosis.

Background And Objective: Pulmonary fibrosis (PF) is a chronic progressive disease with an extremely high mortality rate and is a complication of COVID-19. Inhalable microspheres have been increasingly used in the treatment of lung diseases such as PF in recent years. Compared to the direct inhalation of drugs, a larger particle size is required to ensure the sustained release of microspheres.

Metal complex-based liposomes: Applications and prospects in cancer diagnostics and therapeutics.

Metal complexes are of increasing interest as pharmaceutical agents in cancer diagnostics and therapeutics, while some of them suffer from issues such as limited water solubility and severe systemic toxicity. These drawbacks severely hampered their efficacy and clinical applications. Liposomes hold promise as delivery vehicles for constructing metal complex-based liposomes to maximize the therapeutic efficacy and minimize the side effects of metal complexes.

Combination of oxaliplatin and POM-1 by nanoliposomes to reprogram the tumor immune microenvironment.

Some chemotherapy can damage tumor cells, releasing damage-related molecular patterns including ATP to improve immunological recognition against the tumor by immunogenic cell death (ICD). However, the immune-stimulating ATP may be rapidly degraded into immunosuppressive adenosine by highly expressed CD39 and CD73 in the tumor microenvironment, which leads to immune escape. Based on the above paradox, a liposome nanoplatform combined with ICD inducer (oxaliplatin) and CD39 inhibitor (POM-1) is designed for immunochemotherapy.

Design and research of bone repair scaffold based on two-way fluid-structure interaction.

Background And Objective: Porous bone repair scaffolds are an important method of repairing bone defects. Fluid flow in the scaffold plays a vital role in tissue differentiation and permeability and fluid shear stress (FSS) are two important factors. The differentiation of bone tissue depends on the osteogenic differentiation of cells, FSS affects cell proliferation and differentiation, and permeability affects the transportation of nutrients and metabolic waste.

Unique flower-like Cur-metal complexes loaded liposomes for primary and metastatic breast cancer therapy.

Mounting researches continue to support a favorable role for the drug metal complex against cancer progress and metastasis. However, pharmaceutical barriers were encountered when drug metal complexes needed further pre-clinical and clinical evaluations due to their poor aqueous solubility. In this research, liposomes loaded metal ion as nano-scaled reaction vehicles were used to carry out a synthesis reaction between metal ion and curcumin (Cur) to prepare Cur-metal drug liposomal formulations.

A facile and universal method to achieve liposomal remote loading of non-ionizable drugs with outstanding safety profiles and therapeutic effect.

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method.

Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting.

Therapeutic efficacy against cancer relies heavily on the ability of the therapeutic agents to reach their final targets. The optimal targets of most cancer therapeutic agents are usually biological macromolecules at the subcellular level, which play a key role in carcinogenesis. Therefore, to improve the therapeutic efficiency of drugs, researchers need to focus on delivering not only the therapeutic agents to the target tissues and cells but also the drugs to the relevant subcellular structures.

Remote loading paclitaxel-doxorubicin prodrug into liposomes for cancer combination therapy.

The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX--DOX (PSD).

Single-ligand dual-targeting irinotecan liposomes: Control of targeting ligand display by pH-responsive PEG-shedding strategy to enhance tumor-specific therapy and attenuate toxicity.

Along with the malignant proliferation of tumor requiring nutrients, the expression of L-type amino acid transporter 1(LAT1) and amino acid transporter B (ATB) in cancer cells is up-regulated that can be used as new targets for active targeting of tumor. However, since normal cells also express amino acid transporters in small amounts, traditional ligand-exposure drug delivery systems are potentially toxic to the body. Therefore, we designed a smart-response drug delivery system that buries the tyrosine ligand in PEG hydration layer at normal tissues and exposes the ligand by cleaving the pH-sensitive bond of PEG at the tumor site.