Advanced Oral Breviscapine Sustained-Release Tablets for Improved Ischemic Stroke Treatment

Introduction

Cardiovascular and cerebrovascular diseases, including ischemic stroke, are among the most formidable adversaries to human health, contributing significantly to global morbidity and mortality [1]. These conditions are typified by high prevalence, high case fatality rates, and a propensity for recurrence, with an alarming upward trend in incidence rates [2]. A notable demographic shift favoring younger patient populations has emerged, prompting an intensified societal and medical emphasis on the care and treatment of cardiovascular and cerebrovascular health [3]. This has led to a burgeoning demand for effective therapeutics, highlighting the substantial and burgeoning market potential for innovative treatments.

Ischemic stroke, a major contributor to neurological disability, is predominantly managed through thrombolytic therapy [4], [5]. However, this approach might lead to reperfusion injuries, further complicating the clinical management of stroke patients [6], [7]. Breviscapine (BRE), sourced from the Erigeron breviscapus (Vant.) Hand.-Mazz., has been extensively utilized in the medical management of post-stroke aftereffects [8], [9]. Its established efficacy in managing stroke-related complications, coronary heart disease and angina, has earned it a place in the clinical guidelines for ischemic stroke and coronary heart disease in China, underpinned by a robust safety profile [10].

Despite its clinical significance, the current administration of BRE, available in both injectable and oral formulations, is fraught with challenges. The injectable form, being invasive, often leads to poor patient acceptance and suboptimal compliance, and its use in conjunction with other acidic medications can result in precipitation and compatibility issues. The oral formulation has a short half-life, first-pass metabolism, and efflux transporter-mediated absorption inhibition in the gastrointestinal tract, which further impedes its poor gastrointestinal absorption and low bioavailability caused by the compound’s intrinsic poor aqueous solubility and permeability [11], [12]. Researchers have conducted multifaceted investigations on BRE sustained-release formulations. Wang et al. created BRE-PLGA microspheres for a month-long drug release, yet dosage adjustment challenges and safety concerns exist for stroke patients [13]. Gao’s nanotube technology demonstrated promising in vitro sustained release, but the oral safety of halloysite nanotubes and bioavailability enhancement require further investigation [14].

In response to these clinical challenges and unmet needs, this work is dedicated to optimize BRE’s therapeutic potential through advanced formulation technology [15], [16]. The study aims to develop a novel dosage form, an absorption-promoting oral BRE sustained-release tablet (Scheme 1). In order to optimize the gastrointestinal absorption of BRE, mesoporous silicon was utilized to increase BRE’s solubility and Cremophor EL (CrEL) was used to open up tight connections between cells. By employing formulation strategies that optimize the solubility and permeability of BRE, this work endeavors to enhance the drug absorption within the gastrointestinal tract and improve the overall bioavailability [17], [18]. The sustained-release tablet design is intended to reduce the frequency of administration, thereby improving patient adherence and mitigating the safety risks associated with missed doses in conventional controlled-release formulations. This research represents a significant stride in the treatment of ischemic stroke, offering an innovative method to enhance the therapeutic benefits of BRE. The development of such formulation provides a more effective, tolerable, and convenient option for patients and healthcare providers alike.

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Materials

BRE (purity 91.8%) was purchased from Yunnan Hongling Biotechnology Company. Cremophor EL, Pluronic P105, Pluronic P85, Kollicoat SR 30D and Kollicoat IR were gifts from BASF, Germany. Vitamin C, NaHSO3 and rutin were purchased from Sinopharm Chemical Reagent Company, and Transwell was purchased from Corning, USA. The mesoporous silica Syloid XDP3050, Syloid XDP3150, Syloid 244FP, Silsol 6035 were gifts from Grace & Co. USA, and the mesoporous silica AEROPERL 300 was a gift from Evonik.

Tingting Hao, Guangwei Jiang, Chenteng Lin, Cyrille Boyer, Rongqin Huang, Advanced Oral Breviscapine Sustained-Release Tablets for Improved Ischemic Stroke Treatment, Biomaterials, 2024, 123030, ISSN 0142-9612, https://doi.org/10.1016/j.biomaterials.2024.123030.

Read also our introduction article on Mesoporous Silica here: