Introduction: The blood-brain barrier (BBB) selectively impedes the transportation of drug molecules into the brain, which makes the drug delivery and targeting of brain tumors very challenging. Areas covered: Having surveyed the recent literature, comprehensive insights are given into the impacts of the BBB on the advanced drug delivery and targeting modalities for brain tumors. Expert opinion: Brain capillary endothelial cells form the BBB in association with astrocytes, pericytes, neurons, and extracellular matrix. Coop of these forms the complex setting of neurovascular unite. The BBB maintains the brain homeostasis by restrictive controlling of the blood circulating nutrients/substances trafficking. Despite substantial progress on therapy of brain tumors, there is no impeccable strategy to safely deliver chemotherapeutics into the brain. Various strategies have been applied to deliver chemotherapeutics into the brain (e.g. BBB opening, direct delivery by infusion, injection, microdialysis, and implants, and smart nanosystems), which hold different pros and cons. Of note, smart nanoscale multifunctional nanomedicines can serve as targeting, imaging, and treatment modality for brain tumors. Given that aggressive brain tumors (e.g. gliomas) are often unresponsive to any treatments, an in-depth understanding of the molecular/cellular complexity of brain tumors might help the development of smart and effective treatment modalities.

The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor penetration across the blood-brain barrier, low bioavailability, and to some extent, short half-lives. Nanoparticle-mediated drug delivery systems (DDSs) are possible emerging alternatives to overcome such limitations. Nanoparticles are ideally 1–100 nm in size and are considered efficient DDSs mainly due to their unique characteristics, including water dispersity, prolonged half-life in blood circulation, smaller size, and biocompatibility. Nano-scale DDSs can reduce the drug dosage frequency and acute toxicity of drugs while enhancing therapeutic success. Different types of nanoparticles, such as chitosan, polymeric, and nanofibers, have been examined in RAS-related studies, especially in hypertension, cardiovascular disease, and COVID-19. In this review article, we summarize the physical and chemical characteristics of each nanoparticle to elaborate on their potential use in RAS-related nano-drug delivery research and clinical application.

Background: Despite the widespread use of newer basal insulins, Natural Protamine Hagedorn (NPH) insulin still represents a well-established basal formulation with its long history of use, featuring the native form of human insulin. However, NPH insulin exhibits an undesirable peak within hours after a single subcutaneous (s.c.) injection, which may lead to hypoglycemia followed by insufficient basal insulin delivery. This may be attributed to the s.c. enzyme activities degrading the protamine in NPH microcrystals. Methods: A thermogelling block copolymer Pluronic^® F127 (PF127) was utilized as a protective carrier for NPH microcrystals and as a modulator for insulin release from NPH. NPH insulin-loaded PF127 gel was prepared with varying concentrations of the polymer (15–25%) under mild conditions. The formulations were characterized for their gelling temperature, morphology, gel erosion, and in vitro insulin release, with trypsin concentrations up to 5 U/mL. Results: Scanning electron microscopy (SEM) showed that the integrity of NPH microcrystals was maintained after preparation. The burst release of insulin from NPH was significantly attenuated over the course of ~16h in the presence of PF127 with or without enzyme activity. Conclusion: NPH-PF127 successfully resisted the acceleration of NPH crystal dissolution and insulin release in vitro in the presence of protamine-degrading enzyme activity, warranting further testing.