Copper-induced injectable hydrogel with nitric oxide for enhanced immunotherapy by amplifying immunogenic cell death and regulating cancer associated fibroblasts.

Background: Immunogenic cell death (ICD) induced by different cancer treatments has been widely evaluated to recruit immune cells and trigger the specific antitumor immunity. However, cancer associated fibroblasts (CAFs) can hinder the invasion of immune cells and polarize the recruited monocytes to M2-type macrophages, which greatly restrict the efficacy of immunotherapy (IT).

Methods: In this study, an injectable hydrogel induced by copper (Cu) has been designed to contain antibody of PD-L1 and nitric oxide (NO) donor.

Polydopamine-coated thalidomide nanocrystals promote DSS-induced murine colitis recovery through Macrophage M2 polarization together with the synergistic anti-inflammatory and anti-angiogenic effects.

High levels of proinflammatory cytokines, macrophage polarization status and immune-mediated angiogenesis play pivotal roles in the pathogenesis of inflammatory bowel disease (IBD). Thalidomide, an anti-inflammatory, immunomodulatory and antiangiogenic agent, is used off-label for treatment of IBD. The therapeutic potential of thalidomide is limited by its poor solubility and side effects associated with its systemic exposure.

Tumor immunotherapy boosted by R837 nanocrystals through combining chemotherapy and mild hyperthermia.

Melanoma is a malignant skin cancer that is prone to metastasis in the early stage and has a poor prognosis. Immunomodulatory therapy for melanoma has been a hot research topic in recent years. However, low immune cell infiltration and loss of tumor immunogenicity may occur in tumors, resulting in low response rates to immunotherapy.

Surface Decoration via Physical Interaction of Cupric Diethyldithiocarbamate Nanocrystals and Its Impact on Biodistribution and Tumor Targeting.

The vascular wall is the first physiologic barrier that circulating nanoparticles (NPs) encounter, which also is a key biological barrier to cancer drug delivery. NPs can continually scavenge the endothelium for biomarkers of cancer, and the chance of NPs' extravasation into the tumors can be enhanced. Here, we envision P-selectin as a target for specific delivery of drug nanocrystals to tumors.

Preferential Oxycodone Loss of Physically Manipulated Abuse Deterrent Oxycodone HCl Extended Release Tablets Prepared for Nasal Insufflation Studies.

A method to reproducibly mill abuse deterrent oxycodone hydrochloride (HCl) extended release (ER) tablets was developed for a nasal insufflation pharmacokinetic (PK) study. Several comminution methods were explored before determining that a conical mill resulted in controlled milling of tablets to a size range equal to or below 1000 μm. However, milling resulted in significant loss of oxycodone from abuse deterrent oxycodone HCl ER tablets compared to minimal oxycodone loss from oxycodone HCl immediate release (IR) tablets.

One Single Site Clinical Study: To Evaluate the Safety and Efficacy of Immunotherapy With Autologous Dendritic Cells, Cytokine-Induced Killer Cells in Primary Hepatocellular Carcinoma Patients.

Dendritic cells (DCs) and cytokine-induced killer (CIK) cells play an important role in the anti-tumor immune response. In this study, we evaluated the clinical effectiveness of DC/CIK-CD24 immunotherapies to primary hepatocellular carcinoma patients who received radical resection. 36 resected primary hepatocellular carcinoma (HCC) patients were enrolled from August 2014 to December 2015.

A modified hydrophobic ion-pairing complex strategy for long-term peptide delivery with high drug encapsulation and reduced burst release from PLGA microspheres.

Poor encapsulation and high initial burst were two major obstacles for the water-soluble peptide drug loaded microspheres preparation using the industrial emulsification method. In the present study, we hypothesized that the hydrophobic ion-pairing (HIP) complex strategy with a further healing of the pores within the microspheres may improve drug encapsulation and initial burst release. DSS was chosen as the most suitable one among the three test ion-pairing agents (SDS, DSS and STC) due to its high binding efficiency with drug and reversible dissociation capacity in presence of counter ions.

A novel nanoparticle drug delivery system based on PEGylated hemoglobin for cancer therapy.

Proteins such as albumin, gelatin, casein, transferrin, and collagen are widely used as drug delivery systems. However, only albumin-based paclitaxel (PTX) formulation Abraxane (PTX-albumin NPs prepared by nab-technology) has been successfully developed for treating metastatic breast cancer clinically due to abundant materials, simple industrial scale-up process, and well tumor-targeting ability. Hemoglobin (Hb) is another protein used for drug delivery with similar advantages.

Proton Oriented-"Smart Depot" for Responsive Release of Ca to Inhibit Peptide Acylation in PLGA Microspheres.

Purpose: The purpose of this study was to characterize and detail the mechanism of a smart Ca release depot (Ca(PO)) about its ability for sustainable inhibition on peptide acylation within PLGA microspheres.

Methods: The octreotide acetate release and acylation kinetics were analyzed by RP-HPLC. Changes of Ca concentration and adsorption behavior were determined by a Calcium Colorimetric Assay Kit.

Starvation-amplified CO generation for enhanced cancer therapy via an erythrocyte membrane-biomimetic gas nanofactory.

Carbon monoxide (CO)-based gas therapy has emerged as an attractive therapeutic strategy for cancer therapy. However, the main challenges are the in situ-triggered and efficient delivery of CO in tumors, which limit its further clinical application. Herein, we developed an erythrocyte membrane-biomimetic gas nanofactory (MGP@RBC) to amplify the in situ generation of CO for combined energy starvation of cancer cells and gas therapy.

Effect of inner pH on peptide acylation within PLGA microspheres.

Polymer degradation within the controlled-release depots comprising of lactide and glycolide (PLGA) forms an acidic microenvironment, in which severe acylation of the peptide by the polymer degradation products takes place. The aim of this study was to make out the role of the inner μpH on peptide acylation within the microspheres and how could it influence the reaction. The effects of pH on the acylation reaction within microspheres were composed of two aspects.

Preparation and Evaluation of Mosapride Citrate Dual-Release Dry Suspension.

In this paper, a novel formulation of dual-release dry suspension of mosapride citrate (DRDS-MC) was designed which can be quickly released in the stomach while having sustained-release effect. Co-grinding mixture of mosapride citrate (MC) together with L-HPC as hydrophilic excipient was prepared in order to improve the solubility of MC. The co-grinding mixture was characterized by solubility studies, DSC, X-RD, SEM, FTIR, and size distribution before the preparation of the DRDS-MC.

A switchable NO-releasing nanomedicine for enhanced cancer therapy and inhibition of metastasis.

Clinical chemotherapy for cancer is limited by the physiological barrier of tumors, resulting in low drug delivery to tumors, poor efficacy of drugs and inability to block tumor metastasis. Here we developed an intelligent switchable nitric oxide (NO)-releasing nanoparticle, IPH-NO, which loads a photosensitizer (IR780) and the chemotherapy drug paclitaxel (PTX) into NO donor-S-nitrosated human serum albumin (HSA-NO). NO exhibits two effects based on its concentration: enhancement of chemotherapy by increasing the enhanced permeability and retention (EPR) effect at low concentrations and direct killing of cancer cells at high concentrations.

Sodium tanshinone IIA sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis.

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated.

Exploring intracellular fate of drug nanocrystals with crystal-integrated and environment-sensitive fluorophores.

Formulating a poorly water-soluble drug substance into nanocrystals offers many advantages. Understanding of the in vivo fate of drug nanocrystals is however very limited. In this study, we utilized the hybrid nanocrystal concept and studied the kinetic process of dissolution in cancer cells.

Enhanced hepatic targeting, biodistribution and antifibrotic efficacy of tanshinone IIA loaded globin nanoparticles.

Tanshinone IIA (TA) has been recently used to treat liver diseases. However, the poor water solubility and fast metabolism obstruct TA in to be used for the treatment of liver diseases. To overcome this, TA was encapsulated into globin to form nanoparticles (TA-Gb-NPs) by our self-assembling method.

Replacing heme with paclitaxel to prepare drug-loaded globin nanoassembles for CD163 targeting.

Protein-based nanoparticles hold great promises in both preclinical and clinical practices, such as oncology diagnosis and treatment, because of their high biocompatibility and biodegradability. However, the complicated preparation and lack of targeting specific cells or tissues may limit their further uses. To overcome these limitations, we developed a novel replacing method for preparing dual-functional protein nanocarrier, such that one function is capable of encapsulating small molecule into protein, whereas the other function is cable of recognizing CD163 receptor [hemoglobin (Hb) scavenger receptor].

Design, synthesis and antiviral activity studies of schizonepetin derivatives.

A series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. The antiviral activity against HSV-1 and influenza virus H3N2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (CPE) inhibition assay in vitro. Compounds M2, M4, M5 and M34 showed higher inhibitory activity against HSV-1 virus with the TC50 values being in micromole.

Enhanced brain targeting of curcumin by intranasal administration of a thermosensitive poloxamer hydrogel.

Objectives: The aim of this study was to develop a curcumin intranasal thermosensitive hydrogel and to improve its brain targeting efficiency.

Methods: The hydrogel gelation temperature, gelation time, drug release and mucociliary toxicity characteristics as well as the nose-to-brain transport in the rat model were evaluated.

Key Findings: The developed nasal hydrogel, composed of Pluronic F127 and Poloxamer 188, had shorter gelation time, longer mucociliary transport time and produced prolonged curcumin retention in the rat nasal cavity at body temperature.

Molecular switch for the assembly of lipophilic drug incorporated plasma protein nanoparticles and in vivo image.

A strategy to manipulate the disulfide bond breaking triggered unfolding, and subsequently assembly of human serum albumin (HSA) in a lipophilic drug-dependent manner is present. In this study, the hydrophobic region, a molecular switch of the HSA, was regulated to form HSA-paclitaxel (HSA-PTX) nanoparticles by a facile route. High-resolution transmission electron microscopy and fluorescence quenching indicate that HSA coassembled with PTX, which acts as a bridge to form core-shell nanoparticles about 50-240 nm in size, and that PTX might bind to the subdomain IIA sites of HSA.