作者投稿
专家审稿
编辑办公
邮件订阅
RSS
-
摘要: 减少用药次数、延长术后镇痛时间是临床局部麻醉的重要需求。然而，无论是当前临床使用的局麻药，还是生物毒素类潜在新型麻醉药均存在时效较短的问题。利用脂质体、聚合物微球等药物载体装载局麻药进行控释，可实现药物的长效、按需释放，从而满足临床需求。本文简要概述可用于局麻药控释的药物载体，并介绍具有代表性的药物控释体系的设计、功能及其用于局部麻醉的最新研究进展，同时对此研究领域的挑战及未来前景进行讨论。Abstract: Reducing the drug administration times and prolonging the postoperative analgesia duration are important requirements of clinical local anesthesia. However, both local anesthetics currently used in the clinic and potentially new anesthetic drugs such as biological toxins have limited pharmaceutical effect. Biomaterials such as liposomes and polymeric microspheres can be designed to load local anesthetics to achieve a prolonged duration and on-demand drug release, accordingly satisfying clinical needs. In this review, we briefly summarized the recent developments in the design of drug delivery systems for controlled release of local anesthetics, and introduced the design principle, the function of several representative drug controlled release systems, and their applications in local anesthesia. We also discussed the challenges and future perspectives in this field.
-
Key words:
- drug carrier /
- local anesthesia /
- controlled release /
- responsive release /
- long-term efficacy
作者贡献：龙凯负责查阅文献和论文撰写；曹佩负责论文撰写和修订；季天骄负责论文主题确定、论文修订。利益冲突：所有作者均声明不存在利益冲突 -
图 2 基于仿生思路设计的新型局麻药缓释体系
A.新型局麻药河豚毒素及其与钠离子通道蛋白结合区域；B.含有与河豚毒素结合序列的两亲性多肽分子序列(载体分子设计)；C.两亲性载体分子自组装载药示意图及载体自组装透射电镜形貌(纳米纤维)；D.不同疏水基团(C12、C18、疏水氨基酸等)修饰的两亲性多肽载体对河豚毒素的缓释情况；E.优选组载体麻醉效力及对应的剂量
-
[1] Jung RM, Rybak M, Milner P, et al. Local anesthetics and advances in their administration-an overview[J]. J Pre-Clin Clin Res, 2017, 11: 94-101. doi: 10.26444/jpccr/75153 [2] El-Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: current perspectives[J]. Local Reg Anesth, 2018, 11: 35-44. doi: 10.2147/LRA.S154512 [3] Jasinski T, Migon D, Sporysz K, et al. The Density of Different Local Anesthetic Solutions, Opioid Adjuvants and Their Clinically Used Combinations: An Experimental Study[J]. Pharmaceuticals (Basel), 2021, 14: 801. doi: 10.3390/ph14080801 [4] Zhao C, Liu A, Santamaria CM, et al. Polymer-tetrodotoxin conjugates to induce prolonged duration local anesthesia with minimal toxicity[J]. Nat Commun, 2019, 10: 2566. doi: 10.1038/s41467-019-10296-9 [5] Hagen NA, Cantin L, Constant J, et al. Tetrodotoxin for Moderate to Severe Cancer-Related Pain: A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Trial[J]. Pain Res Manag, 2017, 2017: 7212713. [6] Visciano P, Schirone M, Berti M, et al. Marine Biotoxins: Occurrence, Toxicity, Regulatory Limits and Reference Methods[J]. Front Microbiol, 2016, 7: 1051. doi: 10.3389/fmicb.2016.01051 [7] Belgi A, Burnley JV, MacRaild CA, et al. Alkyne-Bridged α-Conotoxin Vc1.1 Potently Reverses Mechanical Allodynia in Neuropathic Pain Models[J]. J Med Chem, 2021, 64: 3222-3233. doi: 10.1021/acs.jmedchem.0c02151 [8] Rwei AY, Paris JL, Wang B, et al. Ultrasound-triggered local anaesthesia[J]. Nat Biomed Eng, 2017, 1: 644-653. doi: 10.1038/s41551-017-0117-6 [9] Zhan C, Wang W, Santamaria C, et al. Ultrasensitive Phototriggered Local Anesthesia[J]. Nano Lett, 2017, 17: 660-665. doi: 10.1021/acs.nanolett.6b03588 [10] Richard BM, Rickert DE, Doolittle D, et al. DepoFoamⓇ Bupivacaine (EXPARELTM) is Compatible Following Lidocaine: Pharmacokinetic Study in Mini-pigs[J]. FASEB, 2011, 25: 392. [11] 曾慧琳, 施震, 符旭东. 布比卡因脂质体注射用悬浮液Exparel临床应用研究进展[J]. 中国新药杂志, 2014, 23: 1654-1657. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ201414019.htm Zeng HL, Shi Z, Fu XD. Progress in clinical application of the bupivacaine liposome injectable suspension Exparel[J]. Zhongguo Xinyao Zazhi, 2014, 23: 1654-1657. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ201414019.htm [12] Poon W, Kingston BR, Ouyang B, et al. A framework for designing delivery systems[J]. Nat Nanotechnol, 2020, 15: 819-829. doi: 10.1038/s41565-020-0759-5 [13] Tu Z, Zhong Y, Hu H, et al. Design of therapeutic biomaterials to control inflammation[J]. Nat Rev Mater, 2022, 28: 1-18. [14] Surve DH, Jindal AB. Recent advances in long-acting nanoformulations for delivery of antiretroviral drugs[J]. J Control Release, 2020, 324: 379-404. doi: 10.1016/j.jconrel.2020.05.022 [15] Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications[J]. Adv Drug Deliv Rev, 2013, 65: 36-48. doi: 10.1016/j.addr.2012.09.037 [16] Grimaldi N, Andrade F, Segovia N, et al. Lipid-based nanovesicles for nanomedicine[J]. Chem Soc Rev, 2016, 45: 6520-6545. doi: 10.1039/C6CS00409A [17] Chang HI, Yeh MK. Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy[J]. Int J Nanomedicine, 2012, 7: 49-60. [18] McAlvin JB, Padera RF, Shankarappa SA, et al. Multivesicular liposomal bupivacaine at the sciatic nerve[J]. Biomaterials, 2014, 35: 4557-4564. doi: 10.1016/j.biomaterials.2014.02.015 [19] Epstein-Barash H, Shichor I, Kwon AH, et al. Prolonged duration local anesthesia with minimal toxicity[J]. PNAS, 2009, 106: 7125-7130. doi: 10.1073/pnas.0900598106 [20] Liechty WB, Kryscio DR, Slaughter BV, et al. Polymers for drug delivery systems[J]. Annu Rev Chem Biomol Eng, 2010, 1: 149-173. doi: 10.1146/annurev-chembioeng-073009-100847 [21] D'souza AA, Shegokar R. Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications[J]. Expert Opin Drug Deliv, 2016, 13: 1257-1275. doi: 10.1080/17425247.2016.1182485 [22] Knop K, Hoogenboom R, Fischer D, et al. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives[J]. Angew Chem Int Ed Engl, 2010, 49: 6288-6308. doi: 10.1002/anie.200902672 [23] Lü JM, Wang X, Marin-Muller C, et al. Current advances in research and clinical applications of PLGA-based nanotechnology[J]. Expert Rev Mol Diagn, 2009, 9: 325-341. doi: 10.1586/erm.09.15 [24] Danhier F, Ansorena E, Silva JM, et al. PLGA-based nanoparticles: an overview of biomedical applications[J]. J Control Release, 2012, 161: 505-522. doi: 10.1016/j.jconrel.2012.01.043 [25] Zhang W, Xu W, Ning C, et al. Long-acting hydrogel/microsphere composite sequentially releases dexmedetomidine and bupivacaine for prolonged synergistic analgesia[J]. Biomaterials, 2018, 181: 378-391. doi: 10.1016/j.biomaterials.2018.07.051 [26] He Y, Qin L, Fang Y, et al. Electrospun PLGA nanomembrane: A novel formulation of extended-release bupivacaine delivery reducing postoperative pain[J]. Mat Des, 2020, 193: 108768. [27] Khandare J, Minko T. Polymer-drug conjugates: Progress in polymeric prodrugs[J]. Prog Polym Sci, 2006, 31: 359-397. doi: 10.1016/j.progpolymsci.2005.09.004 [28] Gu Z, Dong Y, Xu S, et al. Molecularly Imprinted Polymer-Based Smart Prodrug Delivery System for Specific Targeting, Prolonged Retention, and Tumor Microenvironment-Trig-gered Release[J]. Angew Chem Int Ed Engl, 2021, 60: 2663-2667. doi: 10.1002/anie.202012956 [29] Dragojevic S, Ryu JS, Raucher D. Polymer-Based Pro-drugs: Improving Tumor Targeting and the Solubility of Small Molecule Drugs in Cancer Therapy[J]. Molecules, 2015, 20: 21750-21769. doi: 10.3390/molecules201219804 [30] Tang J, Meka AK, Theivendran S, et al. Openwork@Dendritic Mesoporous Silica Nanoparticles for Lactate Depletion and Tumor Microenvironment Regulation[J]. Angew Chem Int Ed Engl, 2020, 59: 22054-22062. doi: 10.1002/anie.202001469 [31] Xu C, Lei C, Wang Y, et al. Dendritic Mesoporous Nanoparticles: Structure, Synthesis and Properties[J]. Angew Chem Int Ed Engl, 2022, 61: e202112752. [32] Ghosh D, Lee Y, Thomas S, et al. M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer[J]. Nat Nanotechnol, 2012, 7: 677-682. doi: 10.1038/nnano.2012.146 [33] Wang C, Chen J, Talavage T, et al. Gold nanorod/Fe3O4 nanoparticle "nano-pearl-necklaces" for simultaneous targeting, dual-mode imaging, and photothermal ablation of cancer cells[J]. Angew Chem Int Ed Engl, 2009, 48: 2759-2763. doi: 10.1002/anie.200805282 [34] Wu M, Zhang X, Zhang W, et al. Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis[J]. Nat Commun, 2022, 13: 1371. doi: 10.1038/s41467-022-29018-9 [35] Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins[J]. Science, 2022, 375: 1254-1261. doi: 10.1126/science.abf0529 [36] Ji T, Li Y, Deng X, et al. Delivery of local anaesthetics by a self-assembled supramolecular system mimicking their interactions with a sodium channel[J]. Nat Biomed Eng, 2021, 5: 1099-1109. doi: 10.1038/s41551-021-00793-y [37] Liu X, Situ A, Kang Y, et al. Irinotecan Delivery by Lipid-Coated Mesoporous Silica Nanoparticles Shows Improved Efficacy and Safety over Liposomes for Pancreatic Cancer[J]. ACS Nano, 2016, 10: 2702-2715. doi: 10.1021/acsnano.5b07781 [38] Heng PWS. Controlled release drug delivery systems[J]. Pharm Dev Technol, 2018, 23: 833. doi: 10.1080/10837450.2018.1534376 [39] Zhan C, Santamaria CM, Wang W, et al. Long-acting liposomal corneal anesthetics[J]. Biomaterials, 2018, 181: 372-377. doi: 10.1016/j.biomaterials.2018.07.054 [40] Weldon C, Ji T, Nguyen MT, et al. Nanoscale Bupivacaine Formulations To Enhance the Duration and Safety of Intravenous Regional Anesthesia[J]. ACS Nano, 2019, 13: 18-25. doi: 10.1021/acsnano.8b05408 [41] Liu Q, Santamaria CM, Wei T, et al. Hollow Silica Nanoparticles Penetrate the Peripheral Nerve and Enhance the Nerve Blockade from Tetrodotoxin[J]. Nano Lett, 2018, 18: 32-37. doi: 10.1021/acs.nanolett.7b02461 [42] Sirsi SR, Borden MA. State-of-the-art materials for ultrasound-triggered drug delivery[J]. Adv Drug Deliv Rev, 2014, 72: 3-14. doi: 10.1016/j.addr.2013.12.010 [43] Rwei AY, Wang W, Kohane DS. Photoresponsive nanoparticles for drug delivery[J]. Nano Today, 2015, 10: 451-467. doi: 10.1016/j.nantod.2015.06.004 [44] Lee H, Song C, Baik S, et al. Device-assisted transdermal drug delivery[J]. Adv Drug Deliv Rev, 2018, 127: 35-45. doi: 10.1016/j.addr.2017.08.009 -
下载:
点击查看大图
图(3)
计量
- 文章访问数: 164
- HTML全文浏览量: 31
- PDF下载量: 58
- 被引次数: 0
