Previously we have developed and statistically validated Quantitative Structure Property Relationship (QSPR) models that correlate drugs' structural, physical and chemical properties as well as experimental conditions with the relative efficiency of remote loading of drugs into liposomes (Cern et al., J. Control. Release 160 (2012) 147-157). Herein, these models have been used to virtually screen a large drug database to identify novel candidate molecules for liposomal drug delivery. Computational hits were considered for experimental validation based on their predicted remote loading efficiency as well as additional considerations such as availability, recommended dose and relevance to the disease. Three compounds were selected for experimental testing which were confirmed to be correctly classified by our previously reported QSPR models developed with Iterative Stochastic Elimination (ISE) and k-Nearest Neighbors (kNN) approaches. In addition, 10 new molecules with known liposome remote loading efficiency that were not used by us in QSPR model development were identified in the published literature and employed as an additional model validation set. The external accuracy of the models was found to be as high as 82% or 92%, depending on the model. This study presents the first successful application of QSPR models for the computer-model-driven design of liposomal drugs.
ISRN Pharm. 2012;2012:636743
[PMID:
22500244]
Eur J Pharm Biopharm. 2012 Feb;80(2):323-31
[PMID:
22061261]
Biol Pharm Bull. 2011;34(6):894-7
[PMID:
21628890]
J Control Release. 2010 Dec 20;148(3):303-10
[PMID:
20869410]
Methods Biochem Anal. 1988;33:337-462
[PMID:
3282152]
J Control Release. 2012 Sep 10;162(2):330-9
[PMID:
22800581]
Biochim Biophys Acta. 1995 Dec 13;1240(2):257-65
[PMID:
8541297]
Drug Deliv. 2012 Feb;19(2):90-101
[PMID:
22283679]
J Liposome Res. 2011 Dec;21(4):261-71
[PMID:
21226547]
Cancer Res. 1994 Feb 15;54(4):987-92
[PMID:
8313389]
Biochim Biophys Acta. 1989 Apr 28;980(3):381-4
[PMID:
2653445]
Int J Nanomedicine. 2012;7:49-60
[PMID:
22275822]
Biochim Biophys Acta. 1993 Sep 19;1151(2):201-15
[PMID:
8373796]
J Am Acad Dermatol. 1990 May;22(5 Pt 1):873-9
[PMID:
2112164]
Nat Biotechnol. 2006 Oct;24(10):1211-7
[PMID:
17033654]
J Control Release. 2011 Dec 10;156(2):128-45
[PMID:
21763369]
J Control Release. 2012 Jun 10;160(2):147-57
[PMID:
22154932]
J Control Release. 2012 Jun 10;160(2):117-34
[PMID:
22484195]
Pharmazie. 2011 Apr;66(4):258-63
[PMID:
21612152]
Curr Pharm Des. 2007;13(34):3494-504
[PMID:
18220786]
Anticancer Res. 2012 Jul;32(7):2919-23
[PMID:
22753756]
Eur J Pharm Biopharm. 2011 Sep;79(1):119-25
[PMID:
21303692]
J Control Release. 2009 Oct 1;139(1):73-80
[PMID:
19508880]
Eur J Pharm Biopharm. 2011 Oct;79(2):285-93
[PMID:
21550400]
J Antimicrob Chemother. 2013 Feb;68(2):257-74
[PMID:
23054997]
J Liposome Res. 2003 Feb;13(1):1-8
[PMID:
12725720]
Methods Enzymol. 2003;367:272-92
[PMID:
14611070]
J Pharm Sci. 1990 Dec;79(12):1045-52
[PMID:
2079648]
Computer Simulation
Computer-Aided Design
Databases, Pharmaceutical
Drug Design
Humans
Liposomes
Pharmaceutical Preparations
