Coaxial double-walled microspheres for drug and gene delivery applications

Polymeric double-walled microspheres were developed by coaxial electrohydrodynamic atomization (CEHDA) and precision particle fabrication (PPF) techniques. Here, we focus on double-walled microspheres consisting of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(D,L-lactic acid) (PDLLA) or poly(L-lactic acid) (PLLA) shell layer. The first study involves bridging the experimental work on the fabrication of double-walled microspheres from CEHDA and the simulation work on the generation of compound droplets from the same process. Process conditions and solution parameters were investigated to ensure the formation of double-walled microspheres with a doxorubicin-loaded PLGA core surrounded by a relatively drug-free PDLLA shell layer. Numerical simulation of CEHDA process was performed based on a computational fluid dynamics (CFD) model in Fluent. The simulation results were compared with the experimental work to illustrate the capability of the CFD model to predict the production of consistent double-walled microspheres. The second study involves drug release and degradation behavior of two double-walled microsphere formulations consisting of a doxorubicin-loaded PLGA core surrounded by a PDLLA shell layer. It was postulated that different molecular weights of the shell layer could modulate the erosion of the outer coating and limit the occurrence of water penetration into the inner drug-loaded core on various time scales, and therefore control the drug release from the microspheres. For both microsphere formulations, the drug release profiles were observed to be similar. Interestingly, both microsphere formulations exhibited occurrence of bulk erosion of PDLLA on a similar time scale despite different PDLLA molecular weights forming the shell layer. The shell layer of the double-walled microspheres served as an effective diffusion barrier during the initial lag phase period and controlled the release rate of the hydrophilic drug independent of the molecular weight of the shell layer. The third study involves designing and evaluating double-walled microspheres loaded with chitosan-p53 nanoparticles (chi-p53, gene encoding p53 tumor suppressor protein) and/or doxorubicin in the shell and core phases, respectively, for combined gene therapy and chemotherapy. The microspheres were monodisperse with a mean diameter of 65 to 75 μm and uniform shell thickness of 8 to 17 μm. The encapsulation efficiency of doxorubicin was significantly higher when it was encapsulated alone compared to co-encapsulation with chi-p53. However, the encapsulation efficiency of chi-p53 was not affected by the presence of doxorubicin. As desired, chi-p53 was released first, followed by simultaneous release of chi-p53 and doxorubicin at a near zero-order rate. Next, the therapeutic efficiencies of doxorubicin and/or chi-p53 in microsphere formulations were compared to free drug(s) and evaluated in terms of growth inhibition, and cellular expression of tumor suppressor p53 and apoptotic caspase 3 proteins in human hepatocellular carcinoma HepG2 cells. Overall, the combined doxorubicin and chi-p53 treatment exhibited enhanced cytotoxicity as compared to either doxorubicin or chi-p53 treatments alone. Moreover, the antiproliferative effect was more substantial when cells were treated with microspheres than those treated with free drugs. Overall, double-walled microspheres present a promising dual anticancer delivery system for combined chemotherapy and gene therapy

Keep Moving to Retain the Healthy Self: The Influence of Physical Exercise in Health Anxiety among Chinese Menopausal Women

Menopause is a period of high incidence of chronic diseases. Women experience various physical and psychological discomforts during menopause, and hormonal changes exacerbate mood swings in menopausal women and also cause them to begin to experience excessive worry and anxiety about their health problems. This study was a cross-sectional survey investigating the relationship between physical activity and women’s health anxiety. Using cluster sampling, a valid sample of 455 females aged 45–50 was collected from 78 communities in five municipal districts in Changsha, China, and AMOS v.23 was adopted to construct a structural equation model to verify the hypotheses. The results indicate that interpersonal competence and emotional intelligence are negatively associated with health anxiety. Furthermore, interpersonal competence and emotional intelligence mediate the relationship between physical exercise and health anxiety, which means that menopausal women with more physical exercise, higher interpersonal competence, and higher emotional intelligence reported lower health anxiety. Finally, to alleviate menopausal women’s health anxiety and reduce their risk of chronic diseases, the government, community, and family should create conditions and opportunities for women to participate in group physical activities

Single-cell sequencing of immune cells from the coronary sinus reveals immune mechanisms of the progression of persistent atrial fibrillation

Summary: Identifying the atlas of immune cells from coronary sinus circulation (CSC) of patients with persistent atrial fibrillation (PerAF) may provide new insights into the role of immune cells in the progression of AF. Single-cell sequencing revealed substantial alterations in immune cells from CSCs of patients with PerAF, especially a markedly elevated abundance of T cells, after which we identified a T cell subset: FGFBP2(+)TRDC(−)CD4(−) T cells (Ftc-T cells), which can promote the proliferation of cardiac fibroblasts (CFs),and the proportion of Ftc-T had a positive linear with AF recurrence post catheter ablation (CA). Moreover, IFI27 was found to be highly enriched in Ftc-T cells and promoted CFs proliferation and collagen expression. Altogether, our findings represent a unique resource providing in-depth insights into the heterogeneity of the immune cell from CSC of patients with PerAF and highlight the potential role of Ftc-T cells and IFI27 for AF progression

Monodisperse double-walled microspheres loaded with chitosan-p53 nanoparticles and doxorubicin for combined gene therapy and chemotherapy

10.1016/j.jconrel.2012.08.032Journal of Controlled Release1632130-135JCRE

Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease

SARS-CoV-2 3CL protease (3CLpro) is essential for coronavirus replication and of great interest as an antiviral drug target. Here, the authors show that the naturally occurring flavonoid myricetin is a non-peptidomimetic and covalent inhibitor of 3CLpro, and they solve crystal structures of 3CLpro with myricetin and derivatives, which reveal that the pyrogallol group covalently modifies the catalytic cysteine

Combined modality doxorubicin-based chemotherapy and chitosan-mediated p53 gene therapy using double-walled microspheres for treatment of human hepatocellular carcinoma

10.1016/j.biomaterials.2013.03.044Biomaterials34215149-5162BIMA

Protein encapsulation in and release from monodisperse double-wall polymer microspheres

Journal of Pharmaceutical Sciences10251601-1609JPMS

Mechanism of drug release from double-walled PDLLA(PLGA) microspheres

10.1016/j.biomaterials.2013.02.015Biomaterials34153902-3911BIMA

Coaxial electrohydrodynamic atomization process for production of polymeric composite microspheres

10.1016/j.ces.2013.09.020Chemical Engineering Science104330-346CESC