title: A mathematical model for thermosensitive liposomal delivery of Doxorubicin to solid tumour.
abstract: The effectiveness of anticancer treatments is often hampered by the serious side effects owing to toxicity of anticancer drugs and their undesirable uptake by healthy cells in vivo. Thermosensitive liposome-mediated drug delivery has been developed as part of research efforts aimed at improving therapeutic efficacy while reducing the associated side effect. Since multiple steps are involved in the transport of drug-loaded liposomes, drug release, and its uptake, mathematical models become an indispensible tool to analyse the transport processes and predict the outcome of anticancer treatment. In this study, a computational model is developed which incorporates the key physical and biochemical processes involved in drug delivery and cellular uptake. The model has been applied to idealized tumour geometry, and comparisons are made between continuous infusion of doxorubicin and thermosensitive liposome-mediated delivery. Results show that thermosensitive liposome-mediated delivery performs better in reducing drug concentration in normal tissues, which may help lower the risk of associated side effects. Compared with direct infusion over a 2-hour period, thermosensitive liposome delivery leads to a much higher peak intracellular concentration of doxorubicin, which may increase cell killing in tumour thereby enhancing the therapeutic effect of the drug.
authors: Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors: Wenbo
authors: W
authors: Zhan
authors: Xiao Yun
authors: XY
authors: Xu
references: Cancer Res. 2004 Jan 15;64(2):711-8
references: 14744789
references: Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):1177-87
references: 8985041
references: Cancer Res. 1995 Sep 1;55(17):3752-6
references: 7641188
references: Adv Drug Deliv Rev. 1999 Nov 10;40(1-2):39-61
references: 10837779
references: Biochem Pharmacol. 1986 Aug 15;35(16):2817-23
references: 3741470
references: Cancer Res. 2004 Jun 1;64(11):3731-6
references: 15172975
references: Cancer Res. 1991 Jan 1;51(1):265-73
references: 1988088
references: Cancer Res. 1984 Jan;44(1):238-44
references: 6197161
references: Oncol Res. 1995;7(7-8):393-8
references: 8747602
references: Cancer Res. 1994 Jul 1;54(13):3352-6
references: 8012948
references: Cancer Res. 1998 Dec 15;58(24):5749-61
references: 9865733
references: Cancer Res. 1993 Aug 15;53(16):3765-70
references: 8339289
references: Microvasc Res. 1993 Sep;46(2):231-53
references: 8246821
references: Theor Biol Med Model. 2011 Dec 07;8:45
references: 22152406
references: Theor Biol Med Model. 2009 Aug 09;6:16
references: 19664243
references: Cancer Res. 1987 Jun 15;47(12):3039-51
references: 3555767
references: Cancer Res. 1993 Jul 1;53(13):3046-51
references: 8319211
references: Cancer Res. 1983 Jul;43(7):3417-21
references: 6850648
references: J Gen Physiol. 1981 Oct;78(4):349-64
references: 7288392
references: J Clin Oncol. 1988 Aug;6(8):1321-7
references: 3411343
references: Microvasc Res. 1989 Jan;37(1):77-104
references: 2646512
references: J Control Release. 1999 Aug 27;61(1-2):9-19
references: 10469899
references: Microvasc Res. 1990 Sep;40(2):246-63
references: 2250603
references: Clin Radiol. 1966 Jul;17(3):220-9
references: 5942772
references: J Angiogenes Res. 2010 Aug 11;2:14
references: 20701757
references: Microcirculation. 1997 Mar;4(1):83-101
references: 9110286
references: J Control Release. 2011 Sep 25;154(3):290-7
references: 21640149
references: Cancer Chemother Pharmacol. 1988;21(3):185-90
references: 3129204
references: J Control Release. 1999 Aug 27;61(1-2):93-106
references: 10469906
references: West J Med. 1983 Sep;139(3):332-41
references: 6356608
references: Eur J Cancer Clin Oncol. 1982 Aug;18(8):739-45
references: 6891324
references: N Engl J Med. 1998 Sep 24;339(13):900-5
references: 9744975
references: Cancer Chemother Pharmacol. 1989;24(6):341-8
references: 2791187
references: Br J Cancer. 1993 Jun;67(6):1189-95
references: 7685615
references: J Chromatogr. 1967 May;28(1):69-81
references: 6048444
references: Cancer Res. 1974 Oct;34(10):2814-22
references: 4369924
references: Microvasc Res. 1991 Jan;41(1):5-23
references: 2051954
references: Physiol Rev. 1993 Jan;73(1):1-78
references: 8419962
references: Toxicol Pathol. 1995 Mar-Apr;23(2):115-23
references: 7569664
references: Am J Physiol. 1987 Jul;253(1 Pt 2):H194-204
references: 3605366
references: Cancer Res. 1994 Feb 15;54(4):987-92
references: 8313389
references: Neoplasia. 2000 Jul-Aug;2(4):325-38
references: 11005567
references: Pharm Res. 2001 Jun;18(6):761-70
references: 11474779