Dendrimers as drugs: Discovery and preclinical and clinical development of dendrimer-based microbicides for HIV and STI prevention

被引:236
作者
McCarthy, Tom D. [1 ]
Karellas, Peter [1 ]
Henderson, Scott A. [1 ]
Giannis, Michael [1 ]
O'Keefe, David F. [1 ]
Heery, Graharn [1 ]
Paull, Jeremy R. A. [1 ]
Matthews, Barry R. [1 ]
Holan, George [1 ]
机构
[1] Starpharma Pty Ltd, Melbourne, Vic 3004, Australia
关键词
nanoscale; nanotechnology; chemical diversity; molecular diversity; dendrimer; SPL7013; VivaGel; antiviral; HIV; HSV-2; microbicide;
D O I
10.1021/mp050023q
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Starpharma focuses on the use of dendrimers as drugs in their own right, in contrast to dendrimers as drug delivery vehicles or diagnostics. This contextual review describes how dendrimers offer a unique platform for exploring chemical diversity on the nanoscale and how the production of dendrimer libraries covering a diverse array of macromolecular structures can be used in drug discovery and development. Using Starpharma's work on the prevention of HIV and sexually transmitted infections (STIs) through the development of microbicide candidates as an example, the process from which SPL7013 emerged as a development candidate is described. Following a range of preclinical studies, Starpharma submitted an investigational new drug application (IND) for SPL7013 gel (VivaGel) to the United States Food and Drug Administration (FDA) in June 2003, the first such submission for a dendrimer-based drug. The first clinical trial under this IND was completed in 2004.
引用
收藏
页码:312 / 318
页数:7
相关论文
共 25 条
[1]  
[Anonymous], 2001, DENDRIMERS OTHER DEN
[2]  
[Anonymous], UNPUB
[3]   Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes [J].
Bernstein, DI ;
Stanberry, LR ;
Sacks, S ;
Ayisi, NK ;
Gong, YH ;
Ireland, J ;
Mumper, RJ ;
Holan, G ;
Matthews, B ;
McCarthy, T ;
Bournel, N .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (12) :3784-3788
[4]   Dendrimers in drug research [J].
Boas, U ;
Heegaard, PMH .
CHEMICAL SOCIETY REVIEWS, 2004, 33 (01) :43-63
[5]   Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection [J].
Bourne, N ;
Stanberry, LR ;
Kern, ER ;
Holan, G ;
Matthews, B ;
Bernstein, DI .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (09) :2471-2474
[6]  
Brouwer AJ, 2001, EUR J ORG CHEM, V2001, P1903
[7]  
Choi S.K., 2004, SYNTHETIC MULTIVALEN
[8]  
COLLINGER MJ, 2002, CURR OPIN CHEM BIOL, V6, P742
[9]   Clinical development of microbicides for the prevention of HIV infection [J].
D'Cruz, OJ ;
Uckun, FM .
CURRENT PHARMACEUTICAL DESIGN, 2004, 10 (03) :315-336
[10]   In vitro comparison of topical microbicides for prevention of human immunodeficiency virus type 1 transmission [J].
Dezzutti, CS ;
James, VN ;
Ramos, A ;
Sullivan, ST ;
Siddig, A ;
Bush, TJ ;
Grohskopf, LA ;
Paxton, L ;
Subbarao, S ;
Hart, CE .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (10) :3834-3844