Chitosan and chitosan coating nanoparticles for the treatment of brain disease.

Central nervous system diseases are a heavy burden on society and health care systems. Hence, the delivery of drugs to the brain has gained more and more interest. The brain is protected by the blood-brain barrier (BBB), a selective barrier formed by the endothelial cells of the cerebral microvessels, which at the same time acts as a bottleneck for drug delivery by preventing the vast majority of drugs to reach the brain. To overcome this obstacle, drugs can be loaded inside nanoparticles that can carry the drug through the BBB. However, not all particles are able to cross the BBB and a multitude of factors needs to be taken into account when developing a carrier system for this purpose. Depending on the chosen pathway to cross the BBB, nanoparticle material, size and surface properties such as functionalization and charge should be tailored to fit the specific route of BBB crossing.

/pdf/key-for-crossing-the-bbb-with-nanoparticles-the-rational-t4h065inp2.pdf

Key for crossing the BBB with nanoparticles: the rational design

Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise ~50% of all brain cells and are therefore likely to establish direct contact with GBM cells. As other tumor cell types can hijack fibroblasts or immune cells to facilitate tumor growth, GBM cells can actually activate astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM cells growth and limited response to radiation or chemotherapy (i.e., Temozolomide). Nevertheless, even though the interest in the cancer research community is increasing, the role of TAAs during GBM development is still overlooked. Yet, obtaining an in‐depth understanding of the mechanisms by which TAAs influence GBM progression might lead to the development of new therapeutic strategies. This article therefore reports the different levels of GBM progression at which TAAs have been recently described to be involved in, including tumor cells' proliferation/invasion and resistance to therapies, especially through the activity of extracellular vesicles.

/pdf/astrocytes-the-rising-stars-of-the-glioblastoma-2s3yzds4g5.pdf

Astrocytes, the rising stars of the glioblastoma microenvironment.

The development of realistic in vitro blood–brain barrier (BBB) models that recapitulate the physiological parameters and molecular aspect of the neurovascular unit (NVU) is of fundamental importan...

https://journals.sagepub.com/doi/pdf/10.1177/0271678X18788769

In-vitro blood-brain barrier modeling: A review of modern and fast-advancing technologies.

Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment.

Remodeling the blood-brain barrier microenvironment by natural products for brain tumor therapy.

Aim Patients in the hemodialysis stage are prone to psychological pressure of depression and anxiety and have resistance, which affects the clinical treatment effect. Effective psychological intervention plays a very important role in improving patients' psychological pressure and patients' compliance. The aim of this study is to explore the nursing effect of psychological intervention on uremic hemodialysis patients. Methods There were 126 uremic hemodialysis patients admitted to the hospital from August 2020 to December 2021. The patients were randomly divided into the routine nursing care group (n = 63) and psychological intervention group (n = 63). The routine nursing care group received routine nursing care for uremia hemodialysis patients. The psychological intervention group implemented psychological intervention on uremia hemodialysis patients. The methods of psychological intervention mainly include establishing a good nurse-patient relationship, popularizing hemodialysis knowledge, timely psychological counseling for patients, and organizing patient communication meetings. The treatment compliance, Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) of the two groups were compared before and after nursing. SF-36 scale was used to evaluate the quality of life of patients. The incidence of complications and nursing satisfaction were compared between the two groups. Results The treatment compliance rate and nursing satisfaction of hemodialysis uremic patients in the psychological intervention group were significantly higher than the routine nursing care group. The SAS and SDS of hemodialysis uremia patients in the psychological intervention group were significantly lower than the routine nursing care group after psychological intervention, and SF-36 scale was significantly higher than the routine nursing group. The main complications of uremic hemodialysis patients are hypotension, hyperkalemia, internal fistula occlusion, and infection. Compared with the routine nursing care group, the incidence of complications in the psychological intervention group was significantly reduced. Conclusion The implementation of psychological nursing intervention for uremic hemodialysis patients have a very significant effect on reducing the incidence of complications and improving anxiety, depression, treatment compliance, and the quality of life and the nursing satisfaction.

/pdf/study-on-nursing-effect-of-psychological-intervention-on-18ndebsq.pdf

Study on Nursing Effect of Psychological Intervention on Uremic Hemodialysis Patients

ATP-binding cassette (ABC) transporters are an example of ATP-dependent pumps, which limit central nervous system (CNS) uptake of certain drugs and molecules. It provides protection for the CNS from exposure to circulating chemicals, thus becoming major obstacles to CNS pharmacotherapy. P-glycoprotein (P-gp) is one of ABC transporters which has been widely studied. The nanocarrier drug delivery systems receive increasing attention for P-gp modulating activity, because of its pharmaceutical excipients that are used in their fabrication. In this chapter, we review the various strategies used to tackle the problem of P-gp efflux as well as the role of nanocarriers in confronting this issue.

Efflux pump inhibition to enhance brain targeting delivery

The treatment dilemma of triple-negative breast cancer (TNBC) revolves around drug resistance and metastasis. Cancer-associated fibroblasts (CAFs) contribute to cisplatin (Cis) resistance and further metastasis in TNBC, making TNBC a difficult-to-treat disease. The dense stromal barrier which restricts drug delivery, invasive phenotype of tumor cells, and immunosuppressive tumor microenvironment (TME) induced by CAFs serve as three "shields" for TNBC against Cis therapy. Here, we designed a silybin-loaded biomimetic nanoparticle coated with anisamide-modified red blood cell membrane (ARm@SNP) as a "nanospear" for CAFs-targeting, which could shatter the "shields" and significantly exhibit inhibitory effect on 4T1 cells in combination with Cis both in vitro and in vivo. The ARm@SNP/Cis elicited 4T1 tumor growth arrest and destroyed three "shields" as follows: disintegrating the stromal barrier by inhibiting blood vessels growth and the expression of fibronectin; decreasing 4T1 cell invasion and metastasis by affecting the TGF-β/Twist/EMT pathway which impeded EMT activation; reversing the immunosuppressive microenvironment by increasing the activity and infiltration of immunocompetent cells. Based on CAFs-targeting, ARm@SNP reversed the resistance of Cis, remodeled the TME and inhibited invasion and metastasis while significantly improving the therapeutic effect of Cis on 4T1 tumor-bearing mice, providing a promising approach for treating intractable TNBC. 

Biomimetic "nano-spears" for CAFs-targeting: Splintered three "shields" with enhanced cisplatin anti-TNBC efficiency.

As the protective barrier of the central nervous system (CNS), the blood-brain barrier (BBB) maintains the brain microenvironment, neuronal activity, and proper functioning of the CNS. Due to its robustness and cell integrity, it is also an outstanding opponent when it comes to the delivery of therapeutic agents to the brain, which requires the crossing through its highly organized structure. Different strategies to open the BBB for efficient CNS delivery are reviewed in this chapter. Both chemical and physical methods which can temporarily disrupt the overall organization and normal structure of the BBB and promote the penetration of nanoparticles to the CNS are described.

Physically open BBB

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