Lipophilic Conjugates of Drugs: A Tool to Improve Drug Pharmacokinetic and Therapeutic Profiles

doi:10.1007/s11095-021-03093-x

	Lipophilic Conjugates of Drugs: A Tool to Improve Drug Pharmacokinetic and Therapeutic Profiles
	Han, Sifei 1,2; Mei, Lianghe 2; Quach, Tim 3,4; Porter, Chris 1; Trevaskis, Natalie 1
刊名	PHARMACEUTICAL RESEARCH
	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.
资助项目	National Health and Medical Research Council[1177084]
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
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER/PLENUM PUBLISHERS
WOS记录号	WOS:000691820300002
内容类型	期刊论文
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.