Lipophilic Conjugates of Drugs: A Tool to Improve Drug Pharmacokinetic and Therapeutic Profiles
文献类型：期刊论文
| 作者 | Han, Sifei1,2; Mei, Lianghe2; Quach, Tim3,4; Porter, Chris1; Trevaskis, Natalie1 |
| 刊名 | PHARMACEUTICAL RESEARCH
 |
| 出版日期 | 2021-08-31 |
| 页码 | 22 |
| 关键词 | conjugate lipid lymphatic pharmacokinetics prodrug |
| ISSN号 | 0724-8741 |
| DOI | 10.1007/s11095-021-03093-x |
| 通讯作者 | Han, Sifei(Sifei.Han@monash.edu) ; Trevaskis, Natalie(Natalie.Trevaskis@monash.edu) |
| 英文摘要 | Lipophilic conjugates (LCs) of small molecule drugs have been used widely in clinical and pre-clinical studies to achieve a number of pharmacokinetic and therapeutic benefits. For example, lipophilic derivatives of drugs are employed in several long acting injectable products to provide sustained drug exposure for hormone replacement therapy and to treat conditions such as neuropsychiatric diseases. LCs can also be used to modulate drug metabolism, and to enhance drug permeation across membranes, either by increasing lipophilicity to enhance passive diffusion or by increasing protein-mediated active transport. Furthermore, such conjugation strategies have been employed to promote drug association with endogenous macromolecular carriers (e.g. albumin and lipoproteins), and this in turn results in altered drug distribution and pharmacokinetic profiles, where the changes can be 'general' (e.g. prolonged plasma half-life) or 'specific' (e.g. enhanced delivery to specific tissues in parallel with the macromolecular carriers). Another utility of LCs is to enhance the encapsulation of drugs within engineered nanoscale drug delivery systems, in order to best take advantage of the targeting and pharmacokinetic benefits of nanomedicines. The current review provides a summary of the mechanisms by which lipophilic conjugates, including in combination with delivery vehicles, can be used to control drug delivery, distribution and therapeutic profiles. The article is structured into sections which highlight a specific benefit of LCs and then demonstrate this benefit with case studies. The review attempts to provide a toolbox to assist researchers to design and optimise drug candidates, including consideration of drug-formulation compatibility. |
| WOS关键词 | LOW-DENSITY-LIPOPROTEIN ; BLOOD-BRAIN-BARRIER ; AMINOMETHYL)-1-CYCLOHEXANE ACETIC-ACID ; HUMAN SERUM-ALBUMIN ; HIGH-FAT-MEAL ; IN-VITRO ; TESTOSTERONE-UNDECANOATE ; LIPID PRODRUGS ; ESTER PRODRUGS ; DIPIVALYL EPINEPHRINE |
| 资助项目 | National Health and Medical Research Council[1177084] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000691820300002 |
| 出版者 | SPRINGER/PLENUM PUBLISHERS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/297749]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Han, Sifei; Trevaskis, Natalie |
| 作者单位 | 1.Monash Univ, Monash Inst Pharmaceut Sci, Drug Delivery Disposit & Dynam, Parkville, Vic 3052, Australia 2.Chinese Acad Sci, Suzhou Inst Drug Innovat, Shanghai Inst Mat Med, Suzhou 215123, Jiangsu, Peoples R China 3.Monash Univ, Monash Inst Pharmaceut Sci, Med Chem, Parkville, Vic 3052, Australia 4.PureTech Hlth, 6 Tide St, Boston, MA 02210 USA |
| 推荐引用方式 GB/T 7714 | Han, Sifei,Mei, Lianghe,Quach, Tim,et al. Lipophilic Conjugates of Drugs: A Tool to Improve Drug Pharmacokinetic and Therapeutic Profiles[J]. PHARMACEUTICAL RESEARCH,2021:22. |
| APA | Han, Sifei,Mei, Lianghe,Quach, Tim,Porter, Chris,&Trevaskis, Natalie.(2021).Lipophilic Conjugates of Drugs: A Tool to Improve Drug Pharmacokinetic and Therapeutic Profiles.PHARMACEUTICAL RESEARCH,22. |
| MLA | Han, Sifei,et al."Lipophilic Conjugates of Drugs: A Tool to Improve Drug Pharmacokinetic and Therapeutic Profiles".PHARMACEUTICAL RESEARCH (2021):22. |
入库方式： OAI收割
来源：上海药物研究所
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