Effect of tumor shape and size on drug delivery to solid tumors

Journal of Biological Engineering

Pu Chen¹  M Soltani¹ 

[1] Waterloo Institute for Nanotechnology, Department of Chemical Engineering, University of Waterloo, Waterloo, ON., Canada N2L 3G1

关键词: Interstitial fluid;    Tumor shape and size;    Computational fluid dynamics;    Solid tumors;    Drug delivery;   

Others  :  813508
DOI  :  10.1186/1754-1611-6-4

 received in 2012-01-06, accepted in 2012-03-30,  发布年份 2012

【 摘 要 】

Tumor shape and size effect on drug delivery to solid tumors are studied, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for predefined tumor geometries. The governing equations are solved using a numerical method, the element-based finite volume method. Interstitial fluid pressure and velocity are used to show the details of drug delivery in a solid tumor, under an assumption that drug particles flow with the interstitial fluid. Drug delivery problems have been most extensively researched in spherical tumors, which have been the simplest to examine with the analytical methods. With our numerical method, however, more complex shapes of the tumor can be studied. The numerical model of fluid flow in solid tumors previously introduced by our group is further developed to incorporate and investigate non-spherical tumors such as prolate and oblate ones. Also the effects of the surface area per unit volume of the tissue, vascular and interstitial hydraulic conductivity on drug delivery are investigated.

【 授权许可】

   
2012 Soltani and Chen; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

Figure 11.

Figure 12.

Figure 13.

Figure 14.

Figure 15.

【 参考文献 】

• [1]Jain RK: Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science 2005, 307:58-62.
• [2]Baxter LT, Jain RK: Transport of fluid and macromolecules in tumors. (I) Role of interstitial pressure and convection. Microvasc Res 1989, 37:77-104.
• [3]Jain RK, Tong RT, Munn LL: Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis. Cancer Res 2007, 67(6):2729-2735.
• [4]Jain RK, Ward-Hartley K: Tumor blood flow-characterization, modifications, and role in hyperthermia. IEEE Trans Sonics and Ultrason 1984., 31
• [5]Jain RK: Determinants of tumor blood flow: A review. Cancer Res 1988a, 48:2641-2658.
• [6]Jones PL, Gallagher BM, Sands H: Autoradiographic analysis of monoclonal antibody distribution in human colon and breast tumor xenografts. Cancer Immunology Immunotherapy 1986, 22(2):139-143.
• [7]Sands H, Jones PL, Shah SA, Plame D, Vessella RL, Gallagher BM: Correlation of vascular permeability and blood flow with monoclonal antibody uptake by human clouser and renal cell xenografts. Cancer Res 1988, 48:188-193.
• [8]Goldacre RJ, Sylven B: On the access of blood-borne dyes to various tumor regions. Brit J Cancer 1962, 16:306-322.
• [9]Blakeslee S: Impenetrable tumors found to block even the newest cancer agents. The New York Times 1989.
• [10]Jain RK: Transport of molecules in the tumor interstitium: A review. Cancer Res 1987a, 47:3039-3051.
• [11]Jain RK: Transport of molecules across tumor vasculature. Cancer Metastasis Rev 1987b, 6:559-594.
• [12]Jain RK, Baxter LT: Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. Cancer Res 1988, 48:7022-7032.
• [13]Jain RK: Transvascular and interstitial transport in tumors. Vascular Endothelium in Health and Disease 1988b, 215-220.
• [14]Soltani M, Chen P: Numerical modeling of fluid flow in solid tumors. PLoS ONE 2011, 6(6):e20344.
• [15]Wang CH, Li J: Three dimensional simulation of IgG delivery to tumors. Chemical Engineering Science 1998, 53(20):3579-3600.
• [16]Tan WHK, Lee T, Wang CH: Simulation of intratumoral release of Etanidazole: Effects on the size of surgical opening. Journal of Pharmaceutical Science 2003, 92(4):773-789.
• [17]Goh YMF, Kong HL, Wang CH: Simulation of the delivery of doxorubicin to hepatoma. Pharmaceutical Research 2001, 18(6):761-770.
• [18]Teo CS, Tan WHK, Lee T, Wang CH: Transient interstitial fluid flow in brain tumors: Effects on drug delivery. Chemical Engineering Science 2005, 60(17):4803-4821.
• [19]Tan WHK, Wang FJ, Lee T, Wang CH: Computer simulation of the delivery of Etanidazole to brain tumor PLGA wafers: Comparison between linear and double burst release systems. Biotechnology and Bioengineering 2003, 82(3):278-288.
• [20]Wang CH, Li J, Teo CS, Lee T: The delivery of BCNU to brain tumors. Journal of Controlled Release 1999, 61(1-2):21-41.
• [21]Pozrikidis C, Farrow DA: A model of fluid flow in solid tumors. Ann Biomed Eng 2003, 31(2):181-194.
• [22]Chapman SJ, Shipley RJ, Jawad R: Multiscale modeling of fluid transport in tumors. Bulletin of Mathematical Biology 2008, 70:2334-2357.
• [23]Baxter LT, Jain RK: Transport of fluid and macromolecules in tumors. (II) Role of heterogeneous perfusion and lymphatics. Microvasc Res 1990, 40:246-263.
• [24]Baxter LT, Jain RK: Transport of fluid and macromolecules in tumors. (III) Role of binding and metabolism. Microvasc Res 1991, 41:5-23.
• [25]Wiig H, Tveit E, Hultborn R, Reed RK, Weiss L: Interstitial fluid pressure in DMBA-induced rat mammary tumors. Stand J C/in Lab Invest 1982, 42:159-164.
• [26]Young JS, Lumsden CE, Stalker AL: The significance of the tissue pressure of normal testicular and of neoplastic (Brown-Pearce carcinoma) tissue in the rabbit. J Pathol Bacteriol 1950, 62:313-333.
• [27]El-Kareh AW, Secomb TW: Effect of increasing vascular hydraulic conductivity on delivery of macromolecular drugs to tumor cells. Int J Radiation Oncology Biol Phys 1995, 32(5):1419-1423.
• [28]Campbell NA: Biology. The Benjamin/Cummings Publishing Co; 1996.
• [29]Salathe EP, An K: A mathematical analysis of fluid movement across capillary walls. Microvasc Res 1976, 11:1-23.
• [30]Scheidegger AE: The physics of flow through porous media. Univ. of Toronto Press; 1963.
• [31]Gross JF, Popel AS: Mathematical models of transport phenomena in normal and neoplastic tissue, Tumor Blood Circulation. CRC Press, h. i peterson edition; 1979.
• [32]de Boer R: Theory of porous media: Highlights in the historical development and current state. Springer; 2000.
• [33]Bear J: Dynamics of fluids in porous media. Dover Publications; 1988.
• [34]Starling EH: On the absorption of fluids from the connective tissue space. J Physiol 1896, 19:312-326.
• [35]Curry FE: Mechanics and thermodynamics of transcapillary exchange, Handbook of Physiology, Section 2: The Cardiovascular System. Amer. Physiol Soc; 1984.
• [36]Gullino PM: Extracellular compartments of solid tumors, Cancer. Plenum; 1975.
• [37]Butler TP, Grantham FH, Gullino PM: Bulk transfer of fluid in the interstitial compartment of mammary tumors. Cancer Res 1975, 35:3084-3088.
• [38]Soltani M, Chen P: Shape design of internal flow with minimum pressure loss. Advanced Science Letters 2009, 2:347-355.
• [39]Linninger AA, Somayaji MR, Erickson T, Guo X, Penn RD: Computational methods for predicting drug transport in anisotropic and heterogeneous brain tissue. Journal of Biomechanics 2008, 41:2176-2187.
• [40]Linninger AA, Somayaji MR, Zhang L, Hariharan MS, Penn RD: Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain. IEEE Transactions on Biomedical Engineering 2008, 55(9):2303-2313.
• [41]Khawli LA, LeBerthon B, Charak BS, Mazumder A, Epstein AL: Enhanced tumor uptake of monoclonal antibodies induced by a novel vasoactive immunoconjugate. Antib Immunoconjug Radiopharm 1991, 4:205.
• [42]LeBerthon B, Khawli LA, Alauddin M, Miller GK, Charak BS, Mazumder A, Epstein AL: Enhanced tumor uptake of macromolecules induced by a novel vasoactive interleukin 2 immunoconjugate. Cancer Res 1991, 51:2694-2698.
• [43]Cope DA, Dewhirst MW, Friedman HS, Bigner DD, Zalutsky MR: Enhanced delivery of a monoclonal antibody F(ab’)2 fragment to subcutaneous human glioma xenografts using local hyperthermia. Cancer Res 1990, 50:1803-1809.
• [44]Ivanchenko O, Sindhwani N, Linninger AA: Experimental techniques for studying poroelasticity in brain phantom gels under high flow microinfusion. Journal of Biomechanical Engineering 2010, 132(5):051008.