Current state of nanomedicine drug products: An industry perspective.

Nanomedicine drug products have reached an unprecedented high in terms of global commercial acceptance and media exposure with the approvals of the mRNA COVID-19 vaccines in 2021. In this paper, we examine the current state of the art for nanomedicine technologies as applied for pharmaceutical products and compare those trends with results from a recent IQ Consortium industry survey on nanomedicine drug products. We find that 1) industry companies continue to push the envelope in terms of new technologies for characterizing their specific drug products, 2) new analytical technologies continue to be utilized by industry to characterize the increasingly complex nanomedicine drug products and 3) alignment and communication are key between industry and regulatory authorities to better understand the regulatory filings that are being submitted.

Effects of antibiotics on the anti-tumor efficacy of immune checkpoint inhibitor therapy.

Purpose: Immunotherapy using immune checkpoint inhibitors (ICIs) has shown several benefits over traditional therapies. However, the eligible population remains small. Antibiotic (ATB) use might reduce immunotherapy efficacy by disrupting the gut microbiota.

Inequities in human papillomavirus vaccination among children aged 9-14 years old under constrained vaccine supply in China.

Background: Inequities in access to human papillomavirus (HPV) vaccine are becoming a growing critical issue globally. Few studies investigate the factors determining HPV vaccine uptake disparities when vaccine supply is constrained, especially in low- and middle-income countries. The aim of this study was to investigate inequities of HPV vaccination and related factors under the constrained vaccine supply in China.

A Review on Commercial Oligonucleotide Drug Products.

Oligonucleotide drug products commercially approved in the US and the EU are reviewed. A total of 20 products that includes 1 aptamer, 12 antisense oligonucleotides (ASOs), 6 small interfering ribonucleic acids (siRNAs), and 1 mixture of single-stranded and double-stranded polydeoxyribonucleotides have been identified. A typical oligonucleotide formulation is composed of an oligonucleotide with buffering agent(s), pH adjusting agents, and a tonicity adjusting agent.

High-SNR mid-infrared dual-comb spectroscopy using active phase control cooperating with CWs-dependent phase correction.

Mid-infrared (MIR) dual-comb spectroscopy (DCS) is a highly effective method for molecular metrology of rovibrational transition spectra in a quick accurate manner. However, due to limited comb frequency instability, manipulating coherence between two frequency combs to accomplish high-quality spectral analysis in the MIR region is a huge challenge. Here, we developed a comb-teeth resolved MIR DCS based on active phase control cooperating with a CWs-dependent (CWD) interferogram timing correction.

Iterative Residual Optimization Network for Limited-Angle Tomographic Reconstruction.

Limited-angle tomographic reconstruction is one of the typical ill-posed inverse problems, leading to edge divergence with degraded image quality. Recently, deep learning has been introduced into image reconstruction and achieved great results. However, existing deep reconstruction methods have not fully explored data consistency, resulting in poor performance.

Protective activity of leaf extract on HO-induced oxidative injury in H9C2 rat cardiomyocytes.

In this study, leaf extract (MDLE) was used to test its anti-oxidation capacity , it has been preliminarily analyzed for HO-induced oxidative damage in H9C2 cells and its main active components. The antioxidant capacity through DPPH (1, 1-Diphenyl-2-Picrylhydrazyl), ABTS• [2,2,2'-azino-BIS-(3-ethylbenzo-thiazoline-6-sulfonic acid)] radical ion, •OH (hydroxyl radical), and (superoxide anion) were determined . The proliferation of H9C2 cells was examined by MTT [3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-Tetrazolium bromide].

A Novel Therapeutic Tumor Vaccine Targeting MUC1 in Combination with PD-L1 Elicits Specific Anti-Tumor Immunity in Mice.

Dendritic cells (DCs), as professional antigen-presenting cells (APCs), play a key role in the initiation and regulation of humoral and cellular immunity. DC vaccines loaded with different tumor-associated antigens (TAAs) have been widely used to study their therapeutic effects on cancer. A number of clinical trials have shown that DCs are safe as an antitumor vaccine and can activate certain anti-tumor immune responses; however, the overall clinical efficacy of DC vaccine is not satisfactory, so its efficacy needs to be enhanced.

Single-cell transcriptomes identifies characteristic features of mouse macrophages in liver Mallory-Denk bodies formation.

Mallory-Denk bodies (MDBs) consist of intracellular aggregates of misfolded proteins in ballooned hepatocytes and serve as important markers of progression in certain liver diseases. Resident hepatic macrophage-mediated inflammation influences the development of chronic liver diseases and cancer. Here, the first systematic study of macrophages heterogeneity in mice was conducted to illustrate the pathogenesis of MDB formation using single-nucleus RNA sequencing (snRNA-seq).

A Novel PD-L1-Containing MSLN Targeting Vaccine for Lung Cancer Immunotherapy.

Therapeutic tumor vaccines have become an important breakthrough in the treatment of various solid tumors including lung cancer. Dendritic cells (DCs)-based tumor vaccines targeting tumor-associated antigens (TAAs) play a key role in immunotherapy and immunoprevention. However, the weak immunogenicity of TAAs and low immune response rates are a major challenge faced in the application of therapeutic tumor vaccines.

Multi-domain integrative Swin transformer network for sparse-view tomographic reconstruction.

Decreasing projection views to a lower X-ray radiation dose usually leads to severe streak artifacts. To improve image quality from sparse-view data, a multi-domain integrative Swin transformer network (MIST-net) was developed and is reported in this article. First, MIST-net incorporated lavish domain features from data, residual data, image, and residual image using flexible network architectures, where a residual data and residual image sub-network was considered as a data consistency module to eliminate interpolation and reconstruction errors.

Collaboration on evidence synthesis in Africa: a network study of growing research capacity.

Background: Evidence-based practice in medicine and social policy relies heavily on evidence synthesis. To translate evidence into practical guidelines for low- and middle-income countries, local expertise is essential. The objectives of this study are to assess the change in capacity for conducting evidence synthesis in Africa and to identify key African institutions for regional capacity-building.

Altered regulation of LncRNA analysis of human alcoholic hepatitis with Mallory-Denk Bodies (MDBs) is revealed by RNA sequencing.

Mallory-Denk Bodies (MDBs) are prevalent in a variety of liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. Long noncoding RNAs (lncRNAs) are considered as emerging new gene regulators, which participates in many functional activities through diverse mechanisms. We previously reported the mechanisms involved in the formation of liver MDBs in mouse model and in AH livers where MDBs had formed.

Charge reversible hyaluronic acid-modified dendrimer-based nanoparticles for siMDR-1 and doxorubicin co-delivery.

Dendrimer-based nanoparticles have shown promising applications in delivery of small interference RNA (siRNA) to downregulate proteins that contribute to multidrug resistance (MDR). Various types of modification can further enhance the anti-tumor efficacy of dendrimer-based nanoparticles. In this study, generation 4 polyamodoamine (PAMAM) was conjugated with PEG-DOPE.

Recent advancements in liposome technology.

The liposomes have continued to be well-recognized as an important nano-sized drug delivery system with attractive properties, such a characteristic bilayer structure assembling the cellular membrane, easy-to-prepare and high bio-compatibility. Extensive effort has been devoted to the development of liposome-based drug delivery systems during the past few decades. Many drug candidates have been encapsulated in liposomes and investigated for reduced toxicity and extended duration of therapeutic effect.

Folate targeted lipid chitosan hybrid nanoparticles for enhanced anti-tumor efficacy.

Folic acid is often used for active targeting of tumor cells to enhance therapeutic outcomes. Here, folic acid was conjugated with chitosan and folate-conjugated chitosan-lipid hybrid nanoparticles were prepared by ionic gelation method using anionic lipid. These nanoparticles were in size range of 200 to 400 nm with spherical shape.

Monoclonal Antibody 2C5-Modified Mixed Dendrimer Micelles for Tumor-Targeted Codelivery of Chemotherapeutics and siRNA.

Targeted delivery of chemotherapeutics to tumors has the potential to reach a high dose at the tumor while minimizing systemic exposure. Incorporation of antibody within a micellar platform represents a drug delivery system for tumor-targeted delivery of antitumor agents. Such modified immunomicelles can result in an increased accumulation of antitumor agents and enhanced cytotoxicity toward cancer cells.

Lipid-chitosan hybrid nanoparticles for controlled delivery of cisplatin.

Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipids and structural advantages of polymers can be obtained using this system for controlled drug delivery. In this study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid.

Surface-engineered polyethyleneimine-modified liposomes as novel carrier of siRNA and chemotherapeutics for combination treatment of drug-resistant cancers.

Modification of nanoparticle surfaces with PEG has been widely considered the gold standard for many years. However, PEGylation presents controversial and serious challenges including lack of functionality, hindered cellular interaction, allergic reactions, and stimulation of IgM production after repetitive dosing that accelerates blood clearance of the nanoparticles. We report the development of novel liposomal formulations surface-modified with a low molecular weight, branched polyethyleneimine (bPEI)-lipid conjugate for use as an alternative to PEG.

Polymeric Co-Delivery Systems in Cancer Treatment: An Overview on Component Drugs' Dosage Ratio Effect.

Multiple factors are involved in the development of cancers and their effects on survival rate. Many are related to chemo-resistance of tumor cells. Thus, treatment with a single therapeutic agent is often inadequate for successful cancer therapy.

Polyamidoamine dendrimers-based nanomedicine for combination therapy with siRNA and chemotherapeutics to overcome multidrug resistance.

Multidrug resistance (MDR) significantly decreases the therapeutic efficiency of anti-cancer drugs. Its reversal could serve as a potential method to restore the chemotherapeutic efficiency. Downregulation of MDR-related proteins with a small interfering RNA (siRNA) is a promising way to reverse the MDR effect.

Barrier Effects of the Kuroshio Current on the East Asian Northerly Monsoon: A Sensitivity Analysis.

Through the use of satellite scatterometer data, it is observed that the East Asian northerly monsoonal winds decrease drastically when crossing the Kuroshio Current. In a section across the Kuroshio Current region, as revealed by reanalysis data, it is suggested that the upward velocity has a two-cell structure extending to the 500 hPa height, and a strong atmospheric convergence is present below the 900 hPa level. The reanalysis data also show that the northerly wind speed decreases significantly when crossing the Kuroshio Current region below 850 hPa height.