The novel design of an intelligent anti-depression transdermal drug delivery system.

Depression is a type of mental disorder with a significant and persistent low mood as the main clinical feature. It is often accompanied by symptoms such as slow thinking, decreased will, loss of appetite, and weight loss. The current treatment methods for depression are mainly medical treatment, psychotherapy, and physical therapy. These treatments are dependent on the patient's autonomy and the patients may suspend treatment due to forgetting or refusing. Therefore, an anti-depressant intelligent drug release system was designed, which can achieve autonomously controlled doses for the treatment of depression by transdermal drug delivery system. The work of this study is as follows: (1) The first module: the electrothermal material heating layer. Several preparation methods were screened, and multiple sets of graphene (GE) electric thermogenic layers were successfully prepared. After increasing the actual energization area to 1 cm × 1 cm, the GE electric thermogenic layer is used as the heating layer of the electrothermal material of the system, and can reach a uniform surface temperature of (45 ± 0.5) °C within 15 s at a voltage of 6 V keeping the temperature fluctuation range not exceeding ±0.03 °C, and the resistance fluctuation range not exceeding ±20 Ω, which plays a role in controlling the temperature and heat treatment of the drug loaded gel layer. (2) The second module: the drug-loaded gel layer. Based on the L16 (45) orthogonal test, the best formulation and process of N-Isopropyl acrylamide-Acrylamide copolymer (P(NIPAAm-co-AAm)) hydrogel was determined. Then, the percutaneous permeability of Selegiline liposome was studied in vitro. (3) A rat model of depression was established using chronic unpredictable mild stress (CUMS) combined with separation. From the aspects of behavior (body weight, sucrose preference test, forced swimming test, open field test) and biochemical indexes (serum proinflammatory cytokines (IL-1ß, TNF-α), hippocampus HE staining observation), the therapeutic effect of hyperthermia, Selegiline oral administration and transdermal administration was discussed.

High-performance SOD mimetic enzyme Au@Ce for arresting cell cycle and proliferation of acute myeloid leukemia.

SOD-like activity of CeO2 nanoparticles (Ce NPs) is driven by Ce3+/Ce4+, high oxidative stress can oxidize Ce3+ to reduce the ratio of Ce3+/Ce4+, inactivating the SOD activity of Ce NPs. Herein, we found Au@Ce NPs, assembled by Au NPs and Ce NPs, exhibited high-performance of SOD mimetic enzyme activity even upon the oxidation of H2O2. Ce NPs supported by nano-Au can acquire the electrons from Au NPs through the enhanced localized surface plasmon resonance (LSPR), maintaining the stability of Ce3+/Ce4+ and SOD-like activity. Meanwhile, Au@Ce NPs retained the peroxidase function and catalase function. As a result, Au@Ce NPs effectively scavenged O2•- and the derived ROS in AML cells, which are the important signaling source that drives AML cell proliferation and accelerates cell cycle progression. When HL-60 cells were treated by Au@Ce NPs, the removal of endogenous ROS signal significantly arrested cell cycle at G1 phase and suppressed the cell proliferation by blocking the mitogen-activated protein kinases (MAPKs) signaling and the Akt/Cyclin D1 cell cycle signaling. Importantly, this treatment strategy showed therapeutic effect for subcutaneous transplantation of AML model as well as a satisfactory result in diminishing the leukocyte infiltration of liver and spleen particularly. Thus, assembled Au@Ce NPs show the high-performance SOD-like activity, promising the potential in treating AML and regulating abnormal ROS in other diseases safely and efficiently.

Safety, heart specificity, and therapeutic effect evaluation of Guanfu base A-loaded solid nanolipids in treating arrhythmia.

Guanfu base A·HCl (GFA·HCl) solution, approved by the China Food and Drug Administration (CFDA) in 2005, has been used in the treatment of arrhythmia. However, the poor targeting and absorption of GFA·HCl have severely affected its clinical application. In this study, a nanolipid-based, Guanfu base A (GFA) delivery system was designed to improve the deficiency of GFA·HCl and realize better clinical effect. The GFA-loaded solid nanolipids (GFASN) with a core/shell structure, composed of Poloxamer 188, lecithin, and medium-chain fatty acid, were prepared using a high-pressure homogenate emulsification method. Results showed that GFASN possessed well morphology and stability during the process of lyophilization and rehydration at 220-260 nm. Safety evaluation revealed that ear vein injection of GFASN (14 mg/kg) were safe enough and of good biocompatibility. More importantly, GFASN can better alleviate the arrhythmia of rats, especially in ventricular ectopia and ventricular tachycardia, than GFA·HCl solution. Pharmacokinetic behaviors and targeting evaluation in mice demonstrated that nanolipids can help GFA achieve longer circulation time in blood and better heart specificity. Collectively, these promising findings suggested that this kind of nanolipids was an ideal delivery carrier for GFA in the treatment of cardiovascular disease.

Paclitaxel-Loaded Magnetic Nanoparticles: Synthesis, Characterization, and Application in Targeting.

Iron oxide magnetic nanoparticles (MNPs) are good candidates to implement fluid therapy in critical patients in clinic integrated system. Herein, we synthesized paclitaxel (PTX)-loaded MNPs modified with methoxy polyethylene glycol (PEG)-lysine-oleic acid2 (PTX-MNPs-PLO), which is expected to act as a magnetic resonance imaging (MRI) contrast agent and meanwhile for cancer therapy. MNPs were synthesized by thermal decomposition. Dialysis method was applied to prepare PTX-MNPs-PLO with 3 different PEG molecular weights (1000, 2000, and 4000 Da), which were subsequently freeze-dried into powders. PTX-MNPs-PLO was characterized by transmission electron microscope, scanning electron microscope, thermogravimetric analysis, vibrating sample magnetometer, and MRI. What is more is that pharmacokinetics and distribution in vivo were processed, the results of which exhibited that PTX-MNPs-PLO2000 had the longer circulation lifetime compared with Taxol, PTX-MNPs-PLO1000, and PTX-MNPs-PLO4000. Results of magnetic targeting in kidneys suggested that deep buried or ultrasmall magnet is likely to be more preferable. PTX-MNPs-PLO2000 holds great promise in the application of magnetic accumulation, target drug delivery, and thermal therapy.