(1) 前体药物改善生物药剂学性质不佳药物/候选药物的口服吸收
(2) 淋巴系统与大分子药物的药代动力学
(3) 淋巴药物递送与相关疾病治疗

于2022年7月加入我校，此前十年在澳大利亚Monash大学从事脂质前体药物研究，进行甘油酯型药物衍生物口服经淋巴系统吸收的机制研究与应用开发等工作。此类前体药物通过模仿脂质吸收和代谢通路，与天然趋向淋巴系统的内源脂蛋白结合后经胃肠淋巴转运，最终实现优异的药物动力学和药效指标。研究工作明确了前体药物分子的仿生代谢过程，提出了活性药物释放的机制及其调控方法，确证了淋巴靶向的效果及作用，研究成果发表于 Angewandte Chemie Int Ed, Journal of Controlled Release 等高水平期刊。 此外，以共同发明人身份构建了由 8 个 PCT 专利群所构成的前体药物淋巴递送技术体系，该技术平台已授权纳斯达克上市企业PureTech Health（美国波士顿），里程碑合同额超过2.2亿美元，面向临床应用的合作开发目前进展顺利。其中，别孕烷醇酮口服脂质前体药物已于2022年完成I期临床试验。别孕烷醇酮是 FDA 唯一批准的用于治疗重度产后抑郁的药物，但此药物因严重首过效应口服无效，需连续 60-72小时静脉输注，使用极不便；由 72 例健康受试者参与的 I 期临床研究显示其脂质前体药物口服后经淋巴系统转运，可达理想生物利用度。2a期概念验证临床试验已于2023年启动。

1. T Quach#, L Hu#, S Han, SF Lim, D Senyschyn, P Yadav, NL Trevaskis, JS Simpson, CJH Porter. Triglyceride-mimetic Prodrugs of Buprenorphine Enhance Oral Bioavailability via Promotion of Lymphatic Transport. Front. Pharmacology, (2022) doi: 10.3389/fphar.2022.879660
2. E Cao, MJ Watt, CJ Nowell, T Quach, JS Simpson, VDM Ferreira, S Agarwal, H Chu, A Srivastava, D Anderson, G Gracia, A Lam, G Segal, J Hong, L Hu, KL Phang, ABJ E, JA Windsor, ARJ Phillips, DJ Creek, NL Harvey, CJH Porter, NL Trevaskis. Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity. Nat Metab. 3 (2021), 1175-1188
3. R Kochappan, E Cao, S Han, L Hu, T Quach, D Senyschyn, VI Ferreira, G Lee, S Lim, C Nowell, D Bonner, J Mintern, JS Simpson, NL Trevaskis, CJH Porter. Targeted delivery of mycophenolic acid to the mesenteric lymph node using a triglyceride mimetic prodrug approach enhances gut-specific immunomodulation in mice. J. Control. Release, 332 (2021), 636-651
4. S Han, T Quach, L Hu, SF Lim, Gracia, NL Trevaskis, JS Simpson, CJH Porter. The impact of conjugation position and linker chemistry on the lymphatic transport of a series of glyceride and phospholipid mimetic prodrugs. J. Pharm. Sci. 110 (2021), 489-499
5. E Cao, A Lindgren, S Martinsson, L Hu, L Lindfors, K Sigfridsson, U Skantze, E Michaëlsson, NL Trevaskis, CJH Porter. Promoting intestinal lymphatic transport targets a liver-X receptor (LXR) agonist (WAY-252,623) to lymphocytes and enhances immunomodulation. J. Control. Release, 296 (2019), 29-39
6. S Han#, L Hu#, Gracia, T Quach, JS Simpson, GA Edwards, NL Trevaskis, CJH Porter. Lymphatic Transport of a Triglyceride Mimetic Prodrug in a Large Animal Model: Studies in Greyhound Dogs. Mol. Pharmaceutics, 13 (2016): 3351-3361 (Faculty 1000 recommended ‘千名学者组织’荐文)
7. L Hu#, T Quach#, S Han#, SF Lim, NL Trevaskis, JS Simpson, CJH Porter. Glyceride-Mimetic Prodrugs Incorporating Self-Immolative Spacers Promote Lymphatic Transport, Avoid First-Pass Metabolism, and Enhance Oral Bioavailability. Angew Chem Int Ed Engl, 55 (2016), 13700-13705 (Frontispiece 卷首文章)
8. S Han, L Hu, T Quach, JS Simpson, NL Trevaskis, CJH Porter. Constitutive Triglyceride Turn-Over into the Mesenteric Lymph is Unable to Support Efficient Lymphatic Transport of a Bio-mimetic Triglyceride Prodrug. J. Pharm. Sci, 105 (2016):786-96
9. S Han, L Hu, T Quach, JS Simpson, NL Trevaskis, CJH Porter. Profiling the Role of Deacylation- Reacylation in the Lymphatic Transport of a Triglyceride-Mimetic Prodrug. Pharm. Research, 32 (2015), 1830-1844
10. NL Trevaskis, L Hu, S Caliph, S Han, CJH Porter. The mesenteric lymph duct cannulated rat model: Application to the assessment of intestinal lymphatic drug transport. J. Visualized Experiments, 97 (2015), doi: 10.3791/52389
11. S Han, T Quach, L Hu, A Wahab, WN Charman, VJ Stella, NL Trevaskis, JS Simpson, CJH Porter. Targeted delivery of a model immunomodulator to the lymphatic system: Comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies. J. Control. Release, 177 (2014), 1-10 (Cover 封面文章)
12. S Caliph, E Cao, JB Bulitta, L Hu, S Han, CJH Porter, NL Trevaskis. The impact of lymphatic transport on the systemic disposition of lipophilic drugs. J. Pharm. Sci, 102 (2013), 2395-2408
13. P Zhang#, L Hu#, Q Yin, L Feng, Y Li. Transferrin-modified c[RGDfK]-paclitaxel loaded hybrid micelle for sequential blood-brain barrier penetration and glioma targeting therapy. Mol. Pharmaceutics, 9 (2012), 1590-1598
14. P Zhang#, L Hu#, Q Yin, Z Zhang, L Feng, Y Li. Transferrin-conjugated polyphos- phoester hybrid micelle loading paclitaxel for brain-targeting delivery: Synthesis, preparation and in vivo evaluation. J. Control. Release, 159 (2012), 429-434
15. C Zhan, B Li, L Hu, X Wei, L Feng, W Fu, and W Lu. Micelle-Based Brain-Targeted Drug Delivery Enabled by a Nicotine Acetylcholine Receptor Ligand. Angew Chem Int Ed, 50 (2011), 5482-5485
16. P Zhang#, L Hu#, Y Wang, J Wang, L Feng, Y Li. Poly(ε-caprolactone)-block-poly (ethyl ethylene phosphate) micelles for brain-targeting drug delivery: in vitro and in vivo valuation. Pharm. Research, 27 (2010), 2657-2669

韩思飞副研究员
胡罗娟 副研究员
博士研究生：张佳智（2022级）、刘薇（2023级）
硕士研究生：李小花（2022级）、费晓萱（2022级）、黄丹（2022级）、高莉（2022级）、裴隽怡（2023级）、袁银银（2023级）、陈昊东（2023级）、田明亮（2023级)