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Evolution of blood-brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2306-2325页

作者： Liang Han Chen Jiang Jiangsu Key Laboratory of Neuropsychiatric Diseases Research College of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China Key Laboratory of Smart Drug Delivery Ministry of EducationState Key Laboratory of Medical NeurobiologyDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 200032China

Bloode-brain barrier(BBB)strictly controls matter exchange between blood and brain,and severely limits brain penetration of systemically administered drugs,resulting in ineffective drug therapy of brain diseases.However,during the onset and progression of brain diseases,BBB alterations evolve inevitably.In this review,we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer’s disease,Parkinson’s disease,epilepsy,stroke,traumatic brain injury and brain tumor.The advances on optimization of small molecules for BBB crossing and non-systemic administration routes(e.g.,intranasal treatment)for BBB bypassing are not included in this review.

关键词： Blood-brain barrier brain diseases brain-targeting Drug delivery systems Nanoparticles

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Preparation and evaluation of sustained-release solid dispersions co-loading gastrodin with borneol as an oral brain-targeting enhancer

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Acta Pharmaceutica Sinica B 2014年第1期4卷 86-93页

作者： Zheng Cai Xiaolu Lei Zhufen Lin Jie Zhao Feizhen Wu Zhaoxiang Yang Junxue Pu Zhongqiu Liu School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Institute of Pharmaceutical Research Kunming Pharmaceutical Co.Kunming 650100China International Institute for Translational Chinese Medicine Guangzhou University of Chinese MedicineGuangzhou 510006China

Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain.However,stomach irritation may occur when high doses of borneol are used.In the present work,gastrodin,the main bioactive ingredient of the traditional Chinese drug“Tianma”(Rhizoma Gastrodiae)was used as a model drug to explore reasonable application of borneol.Sustained-release solid dispersions(SRSDs)for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder.The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy,differential scanning calorimetry,and powder X-ray diffractometry.The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form.Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model.Subsequently,gastric mucosa irritation and the brain targeting of the SRSDs were evaluated.Compared with the free mixture of gastrodin and borneol,brain targeting of SRSDs was slightly weaker(brain targeting index:1.83 vs.2.09),but stomach irritation obviously reduced.Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.

关键词： Borneol Gastrodin Oral drug delivery brain-targeting Gastric mucosa irritation Sustained-release

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Emerging transporter-targeted nanoparticulate drug delivery systems

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Acta Pharmaceutica Sinica B 2019年第1期9卷 49-58页

作者： Hongyan Su Yan Wang Shuo Liu Yue Wang Qian Liu Guangxuan Liu Qin Chen Department of Pharmacy Cancer Hospital of China Medical University Liaoning Cancer Hospital & Institute

Transporter-targeted nanoparticulate drug delivery systems(nano-DDS) have emerged as promising nanoplatforms for efficient drug delivery. Recently, great progress in transporter-targeted strategies has been made, especially with the rapid developments in nanotherapeutics. In this review, we outline the recent advances in transporter-targeted nano-DDS. First, the emerging transporter-targeted nano-DDS developed to facilitate oral drug delivery are reviewed. These include improvements in the oral absorption of protein and peptide drugs, facilitating the intravenous-to-oral switch in cancer chemotherapy. Secondly, the recent advances in transporter-assisted brain-targeting nano-DDS are discussed,focusing on the specific transporter-based targeting strategies. Recent developments in transportermediated tumor-targeting drug delivery are also discussed. Finally, the possible transport mechanisms involved in transporter-mediated endocytosis are highlighted, with special attention to the latest findings of the interactions between membrane transporters and nano-DDS.

关键词： Transporter Nano-DDS Oral delivery brain-targeting Tumor-targeting

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Studies on tissue distribution of scutellarin and methyl polyethylene glycol (mPEG)-scutellarin prodrug in mice

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Acta Pharmaceutica Sinica B 2012年第3期2卷 274-277页

作者： Juan Lu Xia Zhan Qingfei Liu Xi Chen Xinge Zhao Yiming Wang Guoan Luo Institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100094China Beijing Technology and Business University Beijing 100048China School of Medicine Tsinghua UniversityBeijing 100084China Jiangsu Simcere Pharmaceutical Research Institute Nanjing 210042China

This study was to determine tissue distribution and pharmacokinetics of mPEG-scutellarin prodrug(7e),a chemical entity previously shown to have a beneficial effect in cerebral ischemia/reperfusion(I/R)injury.After injecting scutellarin or prodrug 7e,the concentrations of scutellarin and 7e in tissues were determined and the pharmacokinetic parameters were calculated.The results showed that the distribution of scutellarin in tissues was enhanced by PEGylation.The distribution of 7e in brain was approximately 2.1-fold higher than that of scutellarin,indicating that PEGylation increased the brain penetration of scutellarin.We conclude that 7e could exert more effective protection on cerebral I/R injury in mice.This study also provided a simple and convenient strategy to identify novel drugs with potential protective function for I/R injury in mice.

关键词： PEGylation Scutellarin Tissue distribution Cerebral I/R injury brain-targeting

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