The Development of Drug Delivery Systems for Efficient Intracranial Hemorrhage Therapy

Abstract

Intracerebral hemorrhage (ICH) is the most devastating form of stroke, which accounts for 10-15% of cases and causes high morbidity and mortality. With the continuous exploration of the pathological mechanism of ICH, extensive research focusing on ICH therapy has been conducted. However, the traditional treatment methods, such as surgery for removing the hematoma and pharmacotherapy for improving the clearance of the hematoma and neuroprotection, are greatly limited due to their poor practicality and treatment efficiency. The rapid development of drug delivery systems offers an important prospect for treating ICH as they exhibit great versatility, which can improve the pharmacokinetic behavior of drugs in vivo, increase the drug accumulation in specific cell types or tissues, and enhance the therapeutic effect with diminished toxic effect. In this review, the main molecular pathological mechanisms of ICH are comprehensively described and the limitation of traditional pharmacotherapy are also discussed. Then the development based on drug delivery systems for treating ICH is highlighted. Finally, based on these discussions the challenges of drug delivery systems with a view to providing a new feasible path for the treatment of ICH are summarized.

Neutrophil-like pH-responsive pro-efferocytic nanoparticles improve neurological recovery by promoting erythrophagocytosis after intracerebral hemorrhage

“…The blood-brain barrier (BBB) is a physiologic barrier that not only maintains intracerebral homeostasis, but also restricts the access of most drugs to the brain parenchyma, which impedes the therapy of brain disorders to a great extent 35 , 36 . Although the integrity of the BBB was partially compromised after ICH, which offered a probability for therapeutic agents entering the lesion situs, the accumulation of drugs in the brain relying on passively temporary openness of the BBB only slightly increased due to the timing and degree of the BBB opening varied highly with the severity of hemorrhage 10 , 72 , 73 . Inflammatory cells could actively be recruited to the lesions through chemotactic receptors on their membrane surface which interacted with corresponding ligands overexpressed on stressed endothelial cells at the damaged site.…”

“…More attention is deservedly attracted to the removal of cerebral hematoma, which is the most promising strategy for the management of ICH. However, most of the existing studies concentrate on the downstream events after ICH [10,[76][77][78]. There were few researches about endogenous clearance of hematoma, which mainly focused on how to enhance interaction between microglia/macrophage and erythrocytes by regulating the associated signaling pathways, such as promoting the expression of phagocytic receptors or reducing phagocytosis-inhibiting signal [4,7,[79][80][81].…”

“…However, this approach involves invasive craniotomy and intracranial catheterization, with high risks of infection and additional tissue damage 9 . Additionally, there are numerous patients, with serious diabetes or hypertension and less bleeding, who are not suitable for surgery 10 . Therefore, a workable pharmacological strategy to accelerate the endogenous removal of hematoma is exigently demanded.…”

Advances of nanotechnology for intracerebral hemorrhage therapy

“…For the bioavailability, the drug’s half-life in blood determines the dosage and administration frequency. However, many potential drug candidates have poor bioavailability due to insolubility in water, fast metabolic clearance in the circulation, first pass effect and difficulty in passing the physiological barriers ( Xu et al, 2022 ; Yu W. et al, 2023 ; Zhang et al, 2023 ). To address these challenges, various nanomaterials fabricated through polymerization, self-assembly and microfluidics were employed to modify or carry drugs pursuing enhanced bioavailability.…”

“…7.95 ± 0.64 h). In addition to prolonging the half-life, targeted delivery approaches aiming to transport the drug to specific positions or cells are also highly promising ( Yu W. et al, 2023 ). For example, rosuvastatin, a neuroprotective agent, is hard to directly use in ICH due to its toxicity and poor bioavailability ( White, 2002 ).…”