title: Multiscale kinetic modeling of liposomal Doxorubicin delivery quantifies the role of tumor and drug-specific parameters in local delivery to tumors.
abstract: Nanoparticle encapsulation has been used as a means to manipulate the pharmacokinetic (PK) and safety profile of drugs in oncology. Using pegylated liposomal doxorubicin (PLD) vs. conventional doxorubicin as a model system, we developed and experimentally validated a multiscale computational model of liposomal drug delivery. We demonstrated that, for varying tumor transport properties, there is a regimen where liposomal and conventional doxorubicin deliver identical amounts of doxorubicin to tumor cell nuclei. In mice, typical tumor properties consistently favor improved delivery via liposomes relative to free drug. However, in humans, we predict that some tumors will have properties wherein liposomal delivery delivers the identical amount of drug to its target relative to dosing with free drug. The ability to identify tumor types and/or individual patient tumors with high degree of liposome deposition may be critical for optimizing the success of nanoparticle and liposomal anticancer therapeutics.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e15; doi:10.1038/psp.2012.16; advance online publication 21 November 2012.
authors.affiliation: Merrimack Pharmaceuticals, Cambridge, Massachusetts, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Hendriks
authors.forename: J G
authors.initials: JG
authors.lastname: Reynolds
authors.forename: S G
authors.initials: SG
authors.lastname: Klinz
authors.forename: E
authors.initials: E
authors.lastname: Geretti
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: S C
authors.initials: SC
authors.lastname: Leonard
authors.forename: D F
authors.initials: DF
authors.lastname: Gaddy
authors.forename: C W
authors.initials: CW
authors.lastname: Espelin
authors.forename: U B
authors.initials: UB
authors.lastname: Nielsen
authors.forename: T J
authors.initials: TJ
authors.lastname: Wickham