Department of Pharmaceutics, Institute of Pharmacy, Nirma University, SG Highway, Chharodi, Ahmedabad, Gujarat, 382481, India.
Department of Pharmaceutical Technology, L.J. Institute of Pharmacy, L J University, Sarkhej-Sanand Circle Off. S.G. Road, Ahmedabad, Gujarat, 382210, India.
Drugs. 2022 May;82(7):749-792. doi: 10.1007/s40265-022-01717-z. Epub 2022 May 21.
The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (B) are two of the most complex and sophisticated concierges that defend the central nervous system (CNS) by numerous mechanisms. While they maintain the neuro-ecological homeostasis through the regulated entry of essential biomolecules, their conservative nature challenges the entry of most of the drugs intended for CNS delivery. Targeted delivery challenges for a diverse spectrum of therapeutic agents/drugs (non-small molecules, small molecules, gene-based therapeutics, protein and peptides, antibodies) are diverse and demand specialized delivery and disease-targeting strategies. This review aims to capture the trends that have shaped the current brain targeting research scenario. This review discusses the physiological, neuropharmacological, and etiological factors that participate in the transportation of various drug delivery cargoes across the BBB/B and influence their therapeutic intracranial concentrations. Recent research works spanning various invasive, minimally invasive, and non-invasive brain- targeting approaches are discussed. While the pre-clinical outcomes from many of these approaches seem promising, further research is warranted to overcome the translational glitches that prevent their clinical use. Non-invasive approaches like intranasal administration, P-glycoprotein (P-gp) inhibition, pro-drugs, and carrier/targeted nanocarrier-aided delivery systems (alone or often in combination) hold positive clinical prospects for brain targeting if explored further in the right direction.
血脑屏障 (BBB) 和血脑脊液屏障 (B) 是通过多种机制保护中枢神经系统 (CNS) 的最复杂和最精巧的门卫之一。虽然它们通过调节必需生物分子的进入来维持神经生态平衡，但它们的保守性质阻碍了大多数旨在向 CNS 输送的药物的进入。针对各种治疗剂/药物（非小分子、小分子、基于基因的治疗剂、蛋白质和肽、抗体）的靶向输送挑战是多种多样的，需要专门的输送和疾病靶向策略。本综述旨在捕捉塑造当前大脑靶向研究格局的趋势。本综述讨论了参与各种药物输送载体穿过 BBB/B 运输的生理、神经药理学和病因学因素，并影响它们的治疗性颅内浓度。讨论了跨越各种侵入性、微创性和非侵入性大脑靶向方法的最新研究工作。虽然这些方法中的许多临床前结果似乎很有希望，但需要进一步的研究来克服阻止其临床应用的转化障碍。如果朝着正确的方向进一步探索，非侵入性方法，如鼻内给药、P-糖蛋白 (P-gp) 抑制、前药和载体/靶向纳米载体辅助的输送系统（单独或通常联合使用）为大脑靶向提供了积极的临床前景。
