藥物遞送
![](http://images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/a/a7/Action_photo_of_nasal_spray_on_a_black_background.jpg/220px-Action_photo_of_nasal_spray_on_a_black_background.jpg)
藥物遞送,或稱藥物輸送(英語:Drug delivery),是指將藥物化合物輸送到至人體目標部位或靶器官以實現所需治療效果的方法、製劑、儲存體系、或相關生產技術[1][2]。研究藥物遞送通常運用藥物製備、給藥途徑、位點靶向特異性、代謝和毒性的相關原理,優化藥物療效和安全性,從而提高患者服藥的便利性和依從性(Compliance)[3][4]。藥物遞送旨在通過將藥物與不同的賦形劑、藥物載體和藥物裝置形成製劑(Formulation),以改變藥物的藥物代謝動力學和藥物特異性[5][6][7],並尤其提高藥物的生物利用度和體內作用持續時間以改善藥物的治療效果[8]。藥物遞送研究還可側重於提高服藥的安全性,如疫苗接種和一些藥物正在開發的微針貼片可降低針刺傷害的風險[4][9]。
藥物遞送是一個製劑和給藥途徑高度結合的概念,其中給藥途徑常被認為是藥物遞送研究的一部分[10]。雖然給藥途徑一詞通常情況下可以與藥物遞送互換,但實質上兩者並不同。給藥途徑是指藥物進入人體所採用的路徑[11],而藥物遞送除此之外,還包括遞送系統工程和經由相同途徑遞送藥物的不同藥物劑型和設備[12]。常見的給藥途徑包括口服、腸胃外(注射)、舌下、局部、透皮、鼻腔、眼部、直腸和陰道。除了以上主要的途徑,還可經其他多種途徑進行遞送藥物[13]。
自1950年代第一個控釋製劑獲批以來,雖然新藥開發數量呈現下降趨勢,全新遞送系統的研究卻持續取得進展[14][15][16]。以下諸多因素促成了這種轉變,首先是開發新藥的高成本:2013年的一項綜述表明,開發遞送系統的成本僅為開發一個全新新藥成本的10%[17]。而最近的一項研究發現,不考慮開發藥物遞送系統成本的前提下,2020年將一種新藥推向市場成本的中位數為9.85億美元[18]。慢性病和傳染病患病率增加[16][19],以及對藥物藥理學、藥代動力學和藥效學的更多認識,讓藥物遞送系統研究在藥物研發領域變得越來越重要[5]。
當前進展
目前在藥物遞送方面的進展包括:控釋製劑、靶向遞送、納米藥物、藥物載體、3D打印和生物藥物遞送等方向[20][21]。
納米技術
納米技術在藥物遞送領域正開展廣泛的研究,其主要涉及在原子或亞原子水平上控制物料。納米技術科可用於醫學、能源、航空航天工程等諸多領域,在藥物遞送中的應用只是其用途之一。通過納米技術過程,納米粒可攜帶藥物分子並將藥物遞送至身體的特定靶區域或靶器官。使用納米技術進行藥物遞送有幾個優點包括:精確做到對特定細胞的靶向遞送,提高藥物效力以及降低對靶向細胞的毒性。納米粒還可以將疫苗攜帶並遞送至傳統遞送方法難以到達的細胞中。然而,使用納米顆粒進行藥物遞送仍存在一些技術難題。如其可能對環境產生有害影響。儘管存一些潛在的風險,納米技術在藥物遞送中的應用仍然是未來研究中頗有前途的方向[22]。
靶向遞送
靶向藥物遞送是將藥物遞送至人體目標部位而不影響其他非目標組織的過程[23]。由於其在治療癌症領域和其他慢性疾病領域的潛在優勢,藥物研發人員對靶向藥物遞送方向的研究越來越深入[24][25][26]。為了實現高效的靶向遞送,設計的遞送系統須避開人體對於外源性藥物的防禦機制,並通過循環將藥物遞送至目標作用部位[27]。當今對於許多藥物載體已開展研究,以有效地對特定組織器官進行靶向給藥,包括:脂質體、納米凝膠和其他納米技術[28][24][29]。
控釋製劑
控釋製劑(Controlled-release,CR)或其他改良釋放製劑可以改變藥物在人體中釋放的速率和時間,以產生足夠或持續有效的藥物濃度[30]。第一個成功獲批的控釋製劑是於1950年代研發的藥物右旋安非他命[31]。近期越來越多的控釋製劑藥物及通過皮膚緩慢吸收的透皮貼劑藥物被批准上市[32]。至此,依據藥物不同理化特性進行開發進行開發的控釋製劑藥物被不斷得推向市場,如每隔數月只需一次給藥的抗精神病藥以及性激素長效注射劑[33][34]。
自20世紀90年代後期以來,大多數關於控釋製劑技術的研究都集中在使用納米顆粒以降低藥物清除率[31][35]。
調節藥物釋放和藥物零級釋放
許多科學家致力於創造可以保持恆定藥物水平並保持穩定血藥濃度的口服製劑,即藥物以零級速率釋放的可能性。然而一些人體生理的特殊機制使得發明此類口服製劑頗具挑戰性:由於腸道下部的吸收能力偏弱,因此當口服製劑從胃部移動到腸道時通常藥物吸收速率會下降,而服藥後製劑中釋放的藥物量會持續減少,以上兩個因素導致人體對於藥物的總吸收量會隨着服藥時間而降低。因此口服製劑做到藥物零級釋放非常不易,如藥物苯丙醇胺鹽酸鹽通過新型製劑將穩定一致的血液濃度維持約16小時。[36]
生物藥物的遞送
生物藥,如:多肽、蛋白質、抗體、基因或其他具有生物成分的藥物由於其分子體積較大或整個分子帶有帶有靜電荷,通常會具有人體吸收不佳的問題,並且生物藥物分子一旦進入人體就易被酶促降解[5][37]。由於生物藥物以上的技術問題,近代藥物研究人員一直努力在藥物遞送方面通過使用脂質體、納米顆粒、融合蛋白、蛋白籠納米粒、或利用類毒素生物體輸送等途徑來解決生物藥物遞送難題[5][38][39][40][41]。如最近人們熟知的治療COVID-19的mRNA疫苗,通過化學載體將大分子RNA(核糖核酸) 遞送至細胞內對於RNA藥物來說是最有效的,因為同時蛋白質也可經由此過程在體內遞送至細胞中,而DNA分子通常在體外進行遞送過程[42][43][44]。在各種給藥途徑中,口服給藥以其良好的順應性最受患者青睞。然而,對於大多數生物藥物而言,口服給藥的生物利用度通常太低而無法達到期待的治療水平。先進的遞送系統如:含有滲透增強劑或酶抑制劑的製劑系統,和基於脂質的納米載體和微針可某種程度上提高這些生物藥物的口服生物利用度[45] [46]。
納米粒給藥系統的應用示例
藥物遞送系統經多年的研究,已經有一些良好的藥物遞送應用示例,如藥物遞送入腦:許多藥物若分佈至全身會發生不良反應。由於大腦存在血腦屏障因此對藥物非常敏感,如將藥物直接注射入血容易造成較強的不良反應。隨着針對腦部疾病開發的新製劑技術,包括阿茲海默症和帕金森氏病,藥物研發人員正研究將藥物輸送到大腦而並不影響健康組織的方法。近期,藥物科學家已開發出可透過保護性血腦屏障並將藥物直接遞送至大腦的納米顆粒,這可能是對於中樞神經系統疾病患者的福音[47][48]。
參見
參考文獻
- ^ Drug Delivery Systems (definition). www.reference.md. [2021-04-20]. (原始內容存檔於2017-09-20).
- ^ Rayaprolu, Bindhu Madhavi; Strawser, Jonathan J.; Anyarambhatla, Gopal. Excipients in parenteral formulations: selection considerations and effective utilization with small molecules and biologics. Drug Development and Industrial Pharmacy. 2018-10-03, 44 (10): 1565–1571 [2023-05-07]. ISSN 0363-9045. PMID 29863908. S2CID 46934375. doi:10.1080/03639045.2018.1483392. (原始內容存檔於2022-03-06) (英語).
- ^ Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K. Drug delivery systems: An updated review. International Journal of Pharmaceutical Investigation. 2012, 2 (1): 2–11. ISSN 2230-973X. PMC 3465154
. PMID 23071954. doi:10.4103/2230-973X.96920.
- ^ 4.0 4.1 Li, Junwei; Zeng, Mingtao; Shan, Hu; Tong, Chunyi. Microneedle Patches as Drug and Vaccine Delivery Platform. Current Medicinal Chemistry. 2017-08-23, 24 (22): 2413–2422 [2023-05-07]. PMID 28552053. doi:10.2174/0929867324666170526124053. (原始內容存檔於2021-10-24) (英語).
- ^ 5.0 5.1 5.2 5.3 Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K. Drug delivery systems: An updated review. International Journal of Pharmaceutical Investigation. 2012, 2 (1): 2–11. ISSN 2230-973X. PMC 3465154
. PMID 23071954. doi:10.4103/2230-973X.96920.Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K (2012). "Drug delivery systems: An updated review" (頁面存檔備份,存於互聯網檔案館). International Journal of Pharmaceutical Investigation. 2 (1): 2–11. doi:10.4103/2230-973X.96920. ISSN 2230-973X. PMC 3465154 (頁面存檔備份,存於互聯網檔案館). PMID 23071954 (頁面存檔備份,存於互聯網檔案館).
- ^ Tekade, Rakesh K. (編). Basic fundamentals of drug delivery. 30 November 2018. ISBN 978-0-12-817910-9. OCLC 1078149382.
- ^ Allen, T. M. Drug Delivery Systems: Entering the Mainstream. Science. 2004-03-19, 303 (5665): 1818–1822 [2023-05-07]. Bibcode:2004Sci...303.1818A. ISSN 0036-8075. PMID 15031496. S2CID 39013016. doi:10.1126/science.1095833. (原始內容存檔於2023-02-10) (英語).
- ^ Singh, Akhand Pratap; Biswas, Arpan; Shukla, Aparna; Maiti, Pralay. Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles. Signal Transduction and Targeted Therapy. 2019-08-30, 4 (1): 33. ISSN 2059-3635. PMC 6799838
. PMID 31637012. doi:10.1038/s41392-019-0068-3 (英語).
- ^ Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R. Microneedles for drug and vaccine delivery. Advanced Drug Delivery Reviews. November 2012, 64 (14): 1547–1568. PMC 3419303
. PMID 22575858. doi:10.1016/j.addr.2012.04.005 (英語).
- ^ Nahler, Gerhard. Dictionary of Pharmaceutical Medicine. Springer, Cham. 2017: 96 [2023-05-07]. ISBN 978-3-319-50669-2. doi:10.1007/978-3-319-50669-2_4. (原始內容存檔於2018-06-18).
- ^ route of administration - definition of route of administration in the Medical dictionary - by the Free Online Medical Dictionary, Thesaurus and Encyclopedia.. 2011-06-12 [2021-04-20]. (原始內容存檔於2011-06-12).
- ^ Jain, Kewal K., Jain, Kewal K. , 編, An Overview of Drug Delivery Systems, Drug Delivery Systems, Methods in Molecular Biology (New York, NY: Springer New York), 2020, 2059: 1–54 [2021-04-20], ISBN 978-1-4939-9797-8, PMID 31435914, doi:10.1007/978-1-4939-9798-5_1 (英語)
- ^ COMMON ROUTES OF DRUG ADMINISTRATION. media.lanecc.edu. [2021-04-20]. (原始內容存檔於2021-10-15).
- ^ Park, Kinam. Controlled drug delivery systems: Past forward and future back. Journal of Controlled Release. September 2014, 190: 3–8. PMC 4142099
. PMID 24794901. doi:10.1016/j.jconrel.2014.03.054 (英語).
- ^ Scannell, Jack W.; Blanckley, Alex; Boldon, Helen; Warrington, Brian. Diagnosing the decline in pharmaceutical R&D efficiency. Nature Reviews Drug Discovery. March 2012, 11 (3): 191–200 [2023-05-07]. ISSN 1474-1776. PMID 22378269. S2CID 3344476. doi:10.1038/nrd3681. (原始內容存檔於2023-03-29) (英語).
- ^ 16.0 16.1 ltd, Research and Markets. Pharmaceutical Drug Delivery Market Forecast to 2027 - COVID-19 Impact and Global Analysis by Route of Administration; Application; End User, and Geography. www.researchandmarkets.com. [2021-04-24]. (原始內容存檔於2022-05-19) (english).
- ^ He, Huining; Liang, Qiuling; Shin, Meong Cheol; Lee, Kyuri; Gong, Junbo; Ye, Junxiao; Liu, Quan; Wang, Jingkang; Yang, Victor. Significance and strategies in developing delivery systems for bio-macromolecular drugs. Frontiers of Chemical Science and Engineering. 2013-12-01, 7 (4): 496–507. ISSN 2095-0187. S2CID 97347142. doi:10.1007/s11705-013-1362-1 (英語).
- ^ Wouters, Olivier J.; McKee, Martin; Luyten, Jeroen. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020-03-03, 323 (9): 844–853. ISSN 0098-7484. PMC 7054832
. PMID 32125404. doi:10.1001/jama.2020.1166 (英語).
- ^ PricewaterhouseCoopers. Chronic diseases and conditions are on the rise. PwC. [2021-04-25]. (原始內容存檔於2022-05-28) (en-gx).
- ^ Li, Chong; Wang, Jiancheng; Wang, Yiguang; Gao, Huile; Wei, Gang; Huang, Yongzhuo; Yu, Haijun; Gan, Yong; Wang, Yongjun; Mei, Lin; Chen, Huabing. Recent progress in drug delivery. Acta Pharmaceutica Sinica B. 2019-11-01, 9 (6): 1145–1162. ISSN 2211-3835. PMC 6900554
. PMID 31867161. doi:10.1016/j.apsb.2019.08.003 (英語).
- ^ Drug Delivery Systems. www.nibib.nih.gov. [2021-04-25]. (原始內容存檔於2023-03-17).
- ^ J. Wang, Y. Li, G. Nie, Multifunctional biomolecule nanostructures for cancer therapy, Nat. Rev. Mat. 6 (2021) 766–783
- ^ Tekade, Rakesh K.; Maheshwari, Rahul; Soni, Namrata; Tekade, Muktika; Chougule, Mahavir B. Nanotechnology for the Development of Nanomedicine. Nanotechnology-Based Approaches for Targeting and Delivery of Drugs and Genes. 2017-01-01: 3–61 [2023-05-07]. ISBN 9780128097175. doi:10.1016/B978-0-12-809717-5.00001-4. (原始內容存檔於2023-03-14) (英語).
- ^ 24.0 24.1 Madhusudana Rao, Kummara; Krishna Rao, Kummari S.V.; Ha, Chang-Sik. Functional stimuli-responsive polymeric network nanogels as cargo systems for targeted drug delivery and gene delivery in cancer cells. Design of Nanostructures for Theranostics Applications. 2018-01-01: 243–275 [2023-05-07]. ISBN 9780128136690. doi:10.1016/B978-0-12-813669-0.00006-3. (原始內容存檔於2023-03-14) (英語).
- ^ Patra, Jayanta Kumar; Das, Gitishree; Fraceto, Leonardo Fernandes; Campos, Estefania Vangelie Ramos; Rodriguez-Torres, Maria del Pilar; Acosta-Torres, Laura Susana; Diaz-Torres, Luis Armando; Grillo, Renato; Swamy, Mallappa Kumara; Sharma, Shivesh; Habtemariam, Solomon. Nano based drug delivery systems: recent developments and future prospects. Journal of Nanobiotechnology. December 2018, 16 (1): 71. ISSN 1477-3155. PMC 6145203
. PMID 30231877. doi:10.1186/s12951-018-0392-8 (英語).
- ^ Amidon, Seth; Brown, Jack E.; Dave, Vivek S. Colon-Targeted Oral Drug Delivery Systems: Design Trends and Approaches. AAPS PharmSciTech. August 2015, 16 (4): 731–741. ISSN 1530-9932. PMC 4508299
. PMID 26070545. doi:10.1208/s12249-015-0350-9 (英語).
- ^ Bertrand, Nicolas; Leroux, Jean-Christophe. The journey of a drug-carrier in the body: An anatomo-physiological perspective. Journal of Controlled Release. 2012-07-20, 161 (2): 152–163 [2023-05-07]. ISSN 0168-3659. PMID 22001607. doi:10.1016/j.jconrel.2011.09.098. (原始內容存檔於2016-01-17) (英語).
- ^ Drug Delivery Systems. www.nibib.nih.gov. [2021-04-25]. (原始內容存檔於2023-03-17)."Drug Delivery Systems" (頁面存檔備份,存於互聯網檔案館). www.nibib.nih.gov. Retrieved 2021-04-25.
- ^ Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary. Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications. Medical Principles and Practice. 2016, 25 (2): 60–72. ISSN 1011-7571. PMC 5588529
. PMID 26938856. doi:10.1159/000445116 (英語).
- ^ Perrie, Yvonne. Pharmaceutics- Drug Delivery and Targeting. FASTtrack. 2012: 1–19. ISBN 978-0-85711-059-6.
- ^ 31.0 31.1 Park, Kinam. Controlled drug delivery systems: Past forward and future back. Journal of Controlled Release. September 2014, 190: 3–8. PMC 4142099
. PMID 24794901. doi:10.1016/j.jconrel.2014.03.054 (英語).Park, Kinam (September 2014). "Controlled drug delivery systems: Past forward and future back" (頁面存檔備份,存於互聯網檔案館). Journal of Controlled Release. 190: 3–8. doi:10.1016/j.jconrel.2014.03.054. PMC 4142099 (頁面存檔備份,存於互聯網檔案館). PMID 24794901 (頁面存檔備份,存於互聯網檔案館).
- ^ Yun, Yeon Hee; Lee, Byung Kook; Park, Kinam. Controlled Drug Delivery: Historical perspective for the next generation. Journal of Controlled Release. December 2015, 219: 2–7. PMC 4656096
. PMID 26456749. doi:10.1016/j.jconrel.2015.10.005 (英語).
- ^ Lindenmayer, Jean-Pierre; Glick, Ira D.; Talreja, Hiteshkumar; Underriner, Michael. Persistent Barriers to the Use of Long-Acting Injectable Antipsychotics for the Treatment of Schizophrenia. Journal of Clinical Psychopharmacology. July 2020, 40 (4): 346–349. ISSN 1533-712X. PMID 32639287. S2CID 220412843. doi:10.1097/JCP.0000000000001225 (英語).
- ^ Mishell, D. R. Pharmacokinetics of depot medroxyprogesterone acetate contraception. The Journal of Reproductive Medicine. May 1996, 41 (5 Suppl): 381–390 [2023-05-07]. ISSN 0024-7758. PMID 8725700. (原始內容存檔於2022-10-07).
- ^ Yun, Yeon Hee; Lee, Byung Kook; Park, Kinam. Controlled Drug Delivery: Historical perspective for the next generation. Journal of Controlled Release. December 2015, 219: 2–7. PMC 4656096
. PMID 26456749. doi:10.1016/j.jconrel.2015.10.005 (英語).Yun, Yeon Hee; Lee, Byung Kook; Park, Kinam (December 2015). "Controlled Drug Delivery: Historical perspective for the next generation" (頁面存檔備份,存於互聯網檔案館). Journal of Controlled Release. 219: 2–7. doi:10.1016/j.jconrel.2015.10.005. PMC 4656096 (頁面存檔備份,存於互聯網檔案館). PMID 26456749 (頁面存檔備份,存於互聯網檔案館).
- ^ Liu, Jue-Chen; Farber, Marlene; Chien, Yie W. Comparative Release of Phenylpropanolamine HC1 from Long-Acting Appetite Suppressant Products: Acutrim Vs. Dexatrim. Drug Development and Industrial Pharmacy. 1984-01-01, 10 (10): 1639–1661 [2023-05-09]. ISSN 0363-9045. doi:10.3109/03639048409039072. (原始內容存檔於2022-06-09).
- ^ Jain, Kewal K., Jain, Kewal K. , 編, An Overview of Drug Delivery Systems, Drug Delivery Systems, Methods in Molecular Biology (New York, NY: Springer New York), 2020, 2059: 1–54 [2021-04-20], ISBN 978-1-4939-9797-8, PMID 31435914, doi:10.1007/978-1-4939-9798-5_1 (英語)Jain, Kewal K. (2020), Jain, Kewal K. (ed.), "An Overview of Drug Delivery Systems", Drug Delivery Systems, Methods in Molecular Biology, New York, NY: Springer New York, vol. 2059, pp. 1–54, doi:10.1007/978-1-4939-9798-5_1, ISBN 978-1-4939-9797-8, PMID 31435914 (頁面存檔備份,存於互聯網檔案館), S2CID 201275047, retrieved 2021-04-20
- ^ Strohl, William R. Current progress in innovative engineered antibodies. Protein & Cell. January 2018, 9 (1): 86–120. ISSN 1674-800X. PMC 5777977
. PMID 28822103. doi:10.1007/s13238-017-0457-8 (英語).
- ^ Marschall, Andrea L J; Frenzel, André; Schirrmann, Thomas; Schüngel, Manuela; Dübel, Stefan. Targeting antibodies to the cytoplasm. mAbs. 2011, 3 (1): 3–16. ISSN 1942-0862. PMC 3038006
. PMID 21099369. doi:10.4161/mabs.3.1.14110.
- ^ Uchida M, Maier B, Waghwani HK, Selivanovitch E, Pay SL, Avera J, Yun E, Sandoval RM, Molitoris BA, Zollman A, Douglas T, Hato, T. The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration. Journal of Clinical Investigation. September 2019, 129 (9): 3941–3951. PMC 6715384
. PMID 31424427. doi:10.1172/JCI127511
.
- ^ Ruschig M, Marschall Andrea LJ. Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context. BioDrugs. 2023, 37 (2): 181–203. PMC 9893211
. PMID 36729328. doi:10.1007/s40259-023-00580-y
.
- ^ Zuris, John A; Thompson, DB; Shu, Y; Guilinger, JP; Bessen, JL; Hu, JH; Maeder, ML; Joung, JK; Chen, ZY; Liu, DR. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat Biotechnol. Jan 2015, 33 (1): 73–80. PMC 4289409
. PMID 25357182. doi:10.1038/nbt.3081.
- ^ Schoenmaker, Linde; Witzigmann, D; Kulkarni, JA; Verbeke, R; Kersten, G; Jiskoot, W; Crommelin, DJA. mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. Int J Pharm. April 2021, 601 (120586): 120586. PMC 8032477
. PMID 33839230. doi:10.1016/j.ijpharm.2021.120586.
- ^ Marschall, Andrea L J. Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy. BioDrugs. October 2021, 25 (6): 643–671. PMC 8548996
. PMID 34705260. doi:10.1007/s40259-021-00500-y.
- ^ Haddadzadegan, S; Dorkoosh, F; Bernkop-Schnürch, A. Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers. Adv Drug Deliv Rev. 2022, 182: 114097. PMID 34999121. doi:10.1016/j.addr.2021.114097.
- ^ Bordbar-Khiabani A, Gasik M. Smart hydrogels for advanced drug delivery systems. International Journal of Molecular Sciences: 3665. doi:10.3390/ijms23073665.
- ^ D.S.W. Benoit, C.T. Overby, K.R. Sims Jr., M.A. Ackun-Farmmer, Drug delivery systems, in: W.R. Wagner, S.E. Sakiyama-Elbert, G. Zhang, M.J. Yaszemski (Eds.), Biomaterials Science (Fourth Edition), Academic Press, 2020, pp. 1237–1266 (Ch. 1232.1235.1212).
- ^ Teleanu, Daniel; Chircov, Cristina; Grumezescu, Alexandru; Volceanov, Adrian; Teleanu, Raluca. Blood-Brain Delivery Methods Using Nanotechnology. Pharmaceutics. 2018-12-11, 10 (4): 269. ISSN 1999-4923. PMC 6321434
. PMID 30544966. doi:10.3390/pharmaceutics10040269
(英語).
外部連結
- 化學與工程新聞中的文章 (頁面存檔備份,存於互聯網檔案館)
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