Coaxial electrohydrodynamic atomization: Microparticles for drug delivery applications

Journal of Controlled Release

Volumn 205, Issue , 2015, Pages 70-82

  Davoodi, Pooya ^a   Feng, Fang ^a,b   Xu, Qingxing ^a   Yan, Wei Cheng ^a   Tong, Yen Wah ^a   Srinivasan, M P ^a   Sharma, Vijay Kumar ^c   Wang, Chi Hwa ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b SUZHOU UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^c NATIONAL UNIVERSITY HOSPITAL   (Singapore)

Author keywords

Biodegradable polymers; Coaxial; Core shell microparticles; Drug delivery; EHDA; Electrohydrodynamic atomization; Sustained release

Indexed keywords

ATOMIZATION; BIODEGRADABLE POLYMERS; CHEMOTHERAPY; DISEASES; DRUG DELIVERY; DRUG INTERACTIONS; ELECTROHYDRODYNAMICS; PATIENT TREATMENT;

ADVERSE SIDE EFFECTS; COAXIAL EHDA; COMPUTATIONAL SIMULATION; CORE-SHELL MICROPARTICLES; DRUG DELIVERY APPLICATIONS; ELECTROHYDRODYNAMIC ATOMIZATION; SUSTAINED RELEASE; TREATMENT TECHNIQUES;

CONTROLLED DRUG DELIVERY;

AEROSOL; ANTINEOPLASTIC AGENT; DELAYED RELEASE FORMULATION; DRUG CARRIER; POLYMER;

AEROSOL; ANIMAL; CHEMICAL MODEL; CHEMISTRY; DELAYED RELEASE FORMULATION; DEVICES; DRUG SCREENING; EQUIPMENT DESIGN; HUMAN; MEDICINAL CHEMISTRY; METABOLISM; MOLECULAR DYNAMICS; MOUSE; NEBULIZER; NEOPLASMS; PARTICLE SIZE; PATHOLOGY; PHARMACEUTICS; PROCEDURES; STATISTICAL MODEL; TUMOR CELL LINE;

AEROSOLS; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CHEMISTRY, PHARMACEUTICAL; DELAYED-ACTION PREPARATIONS; DRUG CARRIERS; EQUIPMENT DESIGN; HUMANS; MICE; MODELS, CHEMICAL; MODELS, STATISTICAL; MOLECULAR DYNAMICS SIMULATION; NEBULIZERS AND VAPORIZERS; NEOPLASMS; PARTICLE SIZE; POLYMERS; TECHNOLOGY, PHARMACEUTICAL; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84939995666     PISSN: 01683659     EISSN: 18734995     Source Type: Journal    
DOI: 10.1016/j.jconrel.2014.12.004     Document Type: Article

References (106)

1. X.H. Zhu, S.K. Gan, C.H. Wang, and Y.W. Tong Proteins combination on PHBV microsphere scaffold to regulate Hep3B cells activity and functionality: a model of liver tissue engineering system J. Biomed. Mater. Res. A 83 2007 606 616
2. X.H. Zhu, Y. Tabata, C.H. Wang, and Y.W. Tong Delivery of basic fibroblast growth factor from gelatin microsphere scaffold for the growth of human umbilical vein endothelial cells Tissue Eng. A 14 2008 1939 1947
3. D. He, S. Wang, L. Lei, Z. Hou, P. Shang, X. He, and H. Nie Core-shell particles for controllable release of drug Chem. Eng. Sci. 2014 10.1016/j.ces.2014.08.007
4. Y. Xu, and M.A. Hanna Electrospray encapsulation of water-soluble protein with polylactide. Effects of formulations on morphology, encapsulation efficiency and release profile of particles Int. J. Pharm. 320 2006 30 36
5. M. Nangrejo, E. Bernardo, P. Colombo, U. Farook, Z. Ahmad, E. Stride, and M. Edirisinghe Electrohydrodynamic forming of porous ceramic capsules from a preceramic polymer Mater. Lett. 63 2009 483 485
6. H. Valo, L. Peltonen, S. Vehvilainen, M. Karjalainen, R. Kostiainen, T. Laaksonen, and J. Hirvonen Electrospray encapsulation of hydrophilic and hydrophobic drugs in poly(L-lactic acid) nanoparticles Small 5 2009 1791 1798
7. E. Stride, and N. Saffari Microbubble ultrasound contrast agents: a review Proc. Inst. Mech. Eng. H 217 2003 429 447
8. N. Bock, T.R. Dargaville, and M.A. Woodruff Electrospraying of polymers with therapeutic molecules: state of the art Prog. Polym. Sci. 37 2012 1510 1551
9. G.F. Paciotti, L. Myer, D. Weinreich, D. Goia, N. Pavel, R.E. McLaughlin, and L. Tamarkin Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery Drug Deliv. 11 2004 169 183
10. R. Langer Drug delivery and targeting Nature 392 1998 5 10
11. M. Zamani, M.P. Prabhakaran, and S. Ramakrishna Advances in drug delivery via electrospun and electrosprayed nanomaterials Int. J. Nanomedicine 8 2013 2997 3017
12. P. Patel, S. Irvine, J.R. McEwan, and S.N. Jayasinghe Bio-protocols for directly forming active encapsulations containing living primary cells Soft Matter 4 2008 1219 1229
13. A. Jaworek, and A. Krupa Jet and drops formation in electrohydrodynamic spraying of liquids. A systematic approach Exp. Fluids 27 1999 43 52
14. J. Xie, L.K. Lim, Y. Phua, J. Hua, and C.-H. Wang Electrohydrodynamic atomization for biodegradable polymeric particle production J. Colloid Interface Sci. 302 2006 103 112
15. J. Xie, J.C. Marijnissen, and C.H. Wang Microparticles developed by electrohydrodynamic atomization for the local delivery of anticancer drug to treat C6 glioma in vitro Biomaterials 27 2006 3321 3332
16. A. Jaworek, and A. Krupa Classification of the modes of the spraying J. Aerosol Sci. 30 1999 873 893
17. M.D. Paine, M.S. Alexander, and J.P.W. Stark Nozzle and liquid effects on the spray modes in nanoelectrospray J. Colloid Interface Sci. 305 2007 111 123
18. M. Enayati, M.-W. Chang, F. Bragman, M. Edirisinghe, and E. Stride Electrohydrodynamic preparation of particles, capsules and bubbles for biomedical engineering applications Colloids Surf. A 382 2011 154 164
19. L. Zhang, J. Huang, T. Si, and R.X. Xu Coaxial electrospray of microparticles and nanoparticles for biomedical applications Expert Rev. Med. Devices 9 2012 595 612
20. S. Chakraborty, I.C. Liao, A. Adler, and K.W. Leong Electrohydrodynamics: a facile technique to fabricate drug delivery systems Adv. Drug Deliv. Rev. 61 2009 1043 1054
21. Y. Wu, and R.L. Clark Electrohydrodynamic atomization: a versatile process for preparing materials for biomedical applications J. Biomater. Sci. Polym. Ed. 19 2008 573 601
22. A. Jaworek Electrostatic micro-and nanoencapsulation and electroemulsification: a brief review J. Microencapsul. 25 2008 443 468
23. R.P.A. Hartman, D.J. Brunner, D.M.A. Camelot, J.C.M. Marijnissen, and B. Scarlett Electrohydrodynamic atomization in the cone-jet mode physical modeling of the liquid cone and jet J. Aerosol Sci. 30 1999 823 849
24. O. Lastow, and W. Balachandran Numerical simulation of electrohydrodynamic (EHD) atomization J. Electrost. 64 2006 850 859
25. L.K. Lim, J. Hua, C.-H. Wang, and K.A. Smith Numerical simulation of cone-jet formation in electrohydrodynamic atomization AlChE J. 57 2011 57 78
26. T.P. Forbes, F.L. Degertekin, and A.G. Fedorov Electrohydrodynamics of charge separation in droplet-based ion sources with time-varying electrical and mechanical actuation J. Am. Soc. Mass Spectrom 21 2010 501 510
27. Q. Xu, H. Qin, Z. Yin, J. Hua, D.W. Pack, and C.-H. Wang Coaxial electrohydrodynamic atomization process for production of polymeric composite microspheres Chem. Eng. Sci. 104 2013 330 346
28. J. Xie, J. Jiang, P. Davoodi, M.P. Srinivasan, and C.-H. Wang Electrohydrodynamic atomization: a two-decade effort to produce and process micro-/nanoparticulate materials Chem. Eng. Sci. 2014 10.1016/j.ces.2014.08.061
29. Z.P. Liu, L. Cui, D.G. Yu, Z.X. Zhao, and L. Chen Electrosprayed core-shell solid dispersions of acyclovir fabricated using an epoxy-coated concentric spray head Int. J. Nanomedicine 9 2014 1967 1977
30. H. Nie, Z. Dong, D.Y. Arifin, Y. Hu, and C.H. Wang Core/shell microspheres via coaxial electrohydrodynamic atomization for sequential and parallel release of drugs J. Biomed. Mater. Res. A 95 2010 709 716
31. H. Ho, and J. Lee PEG/PLA core/shell particles from coaxial electrohydrodynamic spray drying Macromol. Res. 19 2011 815 821
32. Y. Jing, Y. Zhu, X. Yang, J. Shen, and C. Li Ultrasound-triggered smart drug release from multifunctional core-shell capsules one-step fabricated by coaxial electrospray method Langmuir 27 2010 1175 1180
33. J. Xie, W.J. Ng, L.Y. Lee, and C.H. Wang Encapsulation of protein drugs in biodegradable microparticles by co-axial electrospray J. Colloid Interface Sci. 317 2008 469 476
34. M. Eltayeb, E. Stride, and M. Edirisinghe Electrosprayed core-shell polymer-lipid nanoparticles for active component delivery Nanotechnology 24 2013 465604
35. Y. Wu, I.C. Liao, S.J. Kennedy, J. Du, J. Wang, K.W. Leong, and R.L. Clark Electrosprayed core-shell microspheres for protein delivery Chem. Commun. 46 2010 4743 4745
36. Q. Xu, S.E. Chin, C.H. Wang, and D.W. Pack Mechanism of drug release from double-walled PDLLA(PLGA) microspheres Biomaterials 34 2013 3902 3911
37. Y. Xia, and D.W. Pack Pulsatile protein release from monodisperse liquid-core microcapsules of controllable shell thickness Pharm. Res. 31 2014 3201 3210
38. Y. Xia, and D.W. Pack Uniform biodegradable microparticle systems for controlled release Chem. Eng. Sci. 2014 10.1016/j.ces.2014.06.049
39. J. Wu, T. Kong, K.W. Yeung, H.C. Shum, K.M. Cheung, L. Wang, and M.K. To Fabrication and characterization of monodisperse PLGA-alginate core-shell microspheres with monodisperse size and homogeneous shells for controlled drug release Acta Biomater. 9 2013 7410 7419
40. S. Torza, and S.G. Mason Three-phase interactions in shear and electrical fields J. Colloid Interface Sci. 33 1970 67 83
41. E.J. Pollauf, and D.W. Pack Use of thermodynamic parameters for design of double-walled microsphere fabrication methods Biomaterials 27 2006 2898 2906
42. S.Y. Hobbs, M.E.J. Dekkers, and V.H. Watkins Effect of interfacial forces on polymer blend morphologies Polymer 29 1988 1598 1602
43. E.J. Sundberg, and D.C. Sundberg Morphology development for three-component emulsion polymers: theory and experiments J. Appl. Polym. Sci. 47 1993 1277 1294
44. A. Matsumoto, Y. Matsukawa, T. Suzuki, H. Yoshino, and M. Kobayashi The polymer-alloys method as a new preparation method of biodegradable microspheres: principle and application to cisplatin-loaded microspheres J. Control. Release 48 1997 19 27
45. E. Stefanis, and C. Panayiotou Prediction of Hansen solubility parameters with a new group-contribution method Int. J. Thermophys. 29 2008 568 585
46. Y.K. Hwang, U. Jeong, and E.C. Cho Production of uniform-sized polymer core-shell microcapsules by coaxial electrospraying Langmuir 24 2008 2446 2451
47. Y.H. Lee, F. Mei, M.Y. Bai, S. Zhao, and D.R. Chen Release profile characteristics of biodegradable-polymer-coated drug particles fabricated by dual-capillary electrospray J. Control. Release 145 2010 58 65
48. Y.H. Lee, M.Y. Bai, and D.R. Chen Multidrug encapsulation by coaxial tri-capillary electrospray Colloids Surf. B 82 2011 104 110
49. S. Zhang, K. Kawakami, M. Yamamoto, Y. Masaoka, M. Kataoka, S. Yamashita, and S. Sakuma Coaxial electrospray formulations for improving oral absorption of a poorly water-soluble drug Mol. Pharm. 8 2011 807 813
50. E.J. Pollauf, K.K. Kim, and D.W. Pack Small-molecule release from poly(D, L-lactide)/poly(D, L-lactide-co-glycolide) composite microparticles J. Pharm. Sci. 94 2005 2013 2022
51. C. Berkland, A. Cox, K. Kim, and D.W. Pack Three-month, zero-order piroxicam release from monodispersed double-walled microspheres of controlled shell thickness J. Biomed. Mater. Res. A 70 2004 576 584
52. H. Nie, Y. Fu, and C.H. Wang Paclitaxel and suramin-loaded core/shell microspheres in the treatment of brain tumors Biomaterials 31 2010 8732 8740
53. Y. Yeo, N. Baek, and K. Park Microencapsulation methods for delivery of protein drugs Biotechnol. Bioproc. Eng. 6 2001 213 230
54. C. Sturesson, and J. Carlfors Incorporation of protein in PLG-microspheres with retention of bioactivity J. Control. Release 67 2000 171 178
55. M. Morlock, H. Koll, G. Winter, and T. Kissel Microencapsulation of rh-erythropoietin, using biodegradable poly(d, l-lactide-co-glycolide): protein stability and the effects of stabilizing excipients Eur. Pharm. Biopharm. 43 1997 29 36
56. H. Sah Stabilization of proteins against methylene chloride/water interface-induced denaturation and aggregation J. Control. Release 58 1999 143 151
57. E. Ron, T. Turek, E. Mathiowitz, M. Chasin, M. Hageman, and R. Langer Controlled release of polypeptides from polyanhydrides Proc. Natl. Acad. Sci. U. S. A. 90 1993 4176 4180
58. D.H. Paik, and S.W. Choi Entrapment of protein using electrosprayed poly(D, L-lactide-co-glycolide) microspheres with a porous structure for sustained release Macromol. Rapid Commun. 35 2014 1033 1038
59. M. Zamani, M.P. Prabhakaran, E.S. Thian, and S. Ramakrishna Protein encapsulated core-shell structured particles prepared by coaxial electrospraying: investigation on material and processing variables Int. J. Pharm. 473 2014 134 143
60. R. Ghaderi, and J. Carlfors Biological activity of lysozyme after entrapment in poly(d, l-lactide-co-glycolide)-microspheres Pharm. Res. 14 1997 1556 1562
61. M. van de Weert, J. Hoechstetter, W.E. Hennink, and D.J.A. Crommelin The effect of a water/organic solvent interface on the structural stability of lysozyme J. Control. Release 68 2000 351 359
62. F. Kang, G. Jiang, A. Hinderliter, P. DeLuca, and J. Singh Lysozyme stability in primary emulsion for PLGA microsphere preparation: effect of recovery methods and stabilizing excipients Pharm. Res. 19 2002 629 633
63. C. Srinivasan, Y.K. Katare, T. Muthukumaran, and A.K. Panda Effect of additives on encapsulation efficiency, stability and bioactivity of entrapped lysozyme from biodegradable polymer particles J. Microencapsul. 22 2005 127 138
64. L.A. Davies, K. Hannavy, N. Davies, A. Pirrie, R.A. Coffee, S.C. Hyde, and D.R. Gill Electrohydrodynamic comminution: a novel technique for the aerosolisation of plasmid DNA Pharm. Res. 22 2005 1294 1304
65. Y. Wu, B. Yu, A. Jackson, W. Zha, L.J. Lee, and B.E. Wyslouzil Coaxial electrohydrodynamic spraying: a novel one-step technique to prepare oligodeoxynucleotide encapsulated lipoplex nanoparticles Mol. Pharm. 6 2009 1371 1379
66. Y. Wu, Z. Fei, L.J. Lee, and B.E. Wyslouzil Coaxial electrohydrodynamic spraying of plasmid DNA/polyethylenimine (PEI) polyplexes for enhanced nonviral gene delivery Biotechnol. Bioeng. 105 2010 834 841
67. Y. Wu, L. Li, Y. Mao, and L.J. Lee Static micromixer-coaxial electrospray synthesis of theranostic lipoplexes ACS Nano 6 2012 2245 2252
68. Y. Cao, B. Wang, Y. Wang, and D. Lou Polymer-controlled core-shell nanoparticles: a novel strategy for sequential drug release RSC Adv. 4 2014 30430 30439
69. G. Polimeni, A.V. Xiropaidis, and U.M. Wikesjo Biology and principles of periodontal wound healing/regeneration Periodontol. 2000 41 2006 30 47
70. P.-C. Chang, A.S. Dovban, L.P. Lim, L.Y. Chong, M.Y. Kuo, and C.-H. Wang Dual delivery of PDGF and simvastatin to accelerate periodontal regeneration in vivo Biomaterials 34 2013 9990 9997
71. P.C. Chang, M.C. Chung, C. Lei, L.Y. Chong, and C.H. Wang Biocompatibility of PDGF-simvastatin double-walled PLGA (PDLLA) microspheres for dentoalveolar regeneration: a preliminary study J. Biomed. Mater. Res. A 100 2012 2970 2978
72. P.C. Chang, L.Y. Chong, A.S. Dovban, L.P. Lim, J.C. Lim, M.Y. Kuo, and C.H. Wang Sequential platelet-derived growth factor-simvastatin release promotes dentoalveolar regeneration Tissue Eng. A 20 2014 356 364
73. P.C. Chang, L.P. Lim, L.Y. Chong, A.S. Dovban, L.Y. Chien, M.C. Chung, C. Lei, M.J. Kao, C.H. Chen, H.C. Chiang, Y.P. Kuo, and C.H. Wang PDGF-simvastatin delivery stimulates osteogenesis in heat-induced osteonecrosis J. Dent. Res. 91 2012 618 624
74. A. Sosnik Production of drug-loaded polymeric nanoparticles by electrospraying technology J. Biomed. Nanotechnol. 10 2014 2200 2217
75. A.D. Duong, S. Sharma, K.J. Peine, G. Gupta, A.R. Satoskar, E.M. Bachelder, B.E. Wyslouzil, and K.M. Ainslie Electrospray encapsulation of toll-like receptor agonist resiquimod in polymer microparticles for the treatment of visceral leishmaniasis Mol. Pharm. 10 2013 1045 1055
76. C. Li, D.-G. Yu, G.R. Williams, and Z.-H. Wang Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process PLoS ONE 9 2014 e92106
77. A. Shapira, Y.D. Livney, H.J. Broxterman, and Y.G. Assaraf Nanomedicine for targeted cancer therapy: towards the overcoming of drug resistance Drug Resist. Updat. 14 2011 150 163
78. B. Felice, M.P. Prabhakaran, A.P. Rodríguez, and S. Ramakrishna Drug delivery vehicles on a nano-engineering perspective Mater. Sci. Eng. C 41 2014 178 195
79. P.M. Bungay, P.F. Morrison, and R.L. Dedrick Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro Life Sci. 46 1990 105 119
80. W.H. Tan, F. Wang, T. Lee, and C.H. Wang Computer simulation of the delivery of etanidazole to brain tumor from PLGA wafers: comparison between linear and double burst release systems Biotechnol. Bioeng. 82 2003 278 288
81. C.C. Wang, J. Li, C.S. Teo, and T. Lee The delivery of BCNU to brain tumors J. Control. Release 61 1999 21 41
82. D.Y. Arifin, K.Y. Lee, and C.H. Wang Chemotherapeutic drug transport to brain tumor J. Control. Release 137 2009 203 210
83. A.D. Duong, G. Ruan, K. Mahajan, J.O. Winter, and B.E. Wyslouzil Scalable, semicontinuous production of micelles encapsulating nanoparticles via electrospray Langmuir 30 2014 3939 3948
84. S. Gun, M. Edirisinghe, and E. Stride Encapsulation of superparamagnetic iron oxide nanoparticles in poly-(lactide-co-glycolic acid) microspheres for biomedical applications Mater. Sci. Eng. C 33 2013 3129 3137
85. E.C. Unger, T.O. Matsunaga, T. McCreery, P. Schumann, R. Sweitzer, and R. Quigley Therapeutic applications of microbubbles Eur. J. Radiol. 42 2002 160 168
86. R. Bekeredjian, P.A. Grayburn, and R.V. Shohet Use of ultrasound contrast agents for gene or drug delivery in cardiovascular medicine J. Am. Coll. Cardiol. 45 2005 329 335
87. L. Yang, Y. Shirakata, K. Tamai, X. Dai, Y. Hanakawa, S. Tokumaru, Y. Yahata, M. Tohyama, K. Shiraishi, H. Nagai, X. Wang, S. Murakami, K. Sayama, Y. Kaneda, and K. Hashimoto Microbubble-enhanced ultrasound for gene transfer into living skin equivalents J. Dermatol. Sci. 40 2005 105 114
88. P.A. Dijkmans, L.J. Juffermans, R.J. Musters, A. van Wamel, F.J. ten Cate, W. van Gilst, C.A. Visser, N. de Jong, and O. Kamp Microbubbles and ultrasound: from diagnosis to therapy Eur. J. Echocardiogr. 5 2004 245 256
89. J.C. McDonald, D.C. Duffy, J.R. Anderson, D.T. Chiu, H. Wu, O.J. Schueller, and G.M. Whitesides Fabrication of microfluidic systems in poly(dimethylsiloxane) Electrophoresis 21 2000 27 40
90. H.M. Wyss, D.L. Blair, J.F. Morris, H.A. Stone, and D.A. Weitz Mechanism for clogging of microchannels Phys. Rev. E: Stat. Nonlinear Soft Matter Phys. 74 2006 061402
91. U. Farook, H.B. Zhang, M.J. Edirisinghe, E. Stride, and N. Saffari Preparation of microbubble suspensions by co-axial electrohydrodynamic atomization Med. Eng. Phys. 29 2007 749 754
92. U. Farook, E. Stride, and M.J. Edirisinghe Preparation of suspensions of phospholipid-coated microbubbles by coaxial electrohydrodynamic atomization J. R. Soc. Interface 6 2009 271 277
93. S. Mahalingam, M.B.J. Meinders, and M. Edirisinghe Formation, stability, and mechanical properties of bovine serum albumin stabilized air bubbles produced using coaxial electrohydrodynamic atomization Langmuir 30 2014 6694 6703
94. M. Parhizkar, E. Stride, and M. Edirisinghe Preparation of monodisperse microbubbles using an integrated embedded capillary T-junction with electrohydrodynamic focusing Lab Chip 14 2014 2437 2446
95. Y. Zhou, S.K. Murugappan, and V.K. Sharma Effect of clot aging and cholesterol content on ultrasound-assisted thrombolysis Transl. Stroke Res. 5 2014 627 634
96. S. Labbaf, S. Deb, G. Cama, E. Stride, and M. Edirisinghe Preparation of multicompartment sub-micron particles using a triple-needle electrohydrodynamic device J. Colloid Interface Sci. 409 2013 245 254
97. A.C. Misra, S. Bhaskar, N. Clay, and J. Lahann Multicompartmental particles for combined imaging and siRNA delivery Adv. Mater. 24 2012 3850 3856
98. W. Kim, and S.S. Kim Multishell encapsulation using a triple coaxial electrospray system Anal. Chem. 82 2010 4644 4647
99. N.A. Peppas, and B. Narasimhan Mathematical models in drug delivery: how modeling has shaped the way we design new drug delivery systems J. Control. Release 190 2014 75 81
100. J. Siepmann, and F. Siepmann Modeling of diffusion controlled drug delivery J. Control. Release 161 2012 351 362
101. A.N. Ford Versypt, D.W. Pack, and R.D. Braatz Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres-a review J. Control. Release 165 2013 29 37
102. J.R. Weiser, and W.M. Saltzman Controlled release for local delivery of drugs: barriers and models J. Control. Release 190 2014 664 673
103. E. Bullitt, G. Gerig, S.M. Pizer, W. Lin, and S.R. Aylward Measuring tortuosity of the intracerebral vasculature from MRA images IEEE Trans. Med. Imaging 22 2003 1163 1171
104. H. Hashizume, P. Baluk, S. Morikawa, J.W. McLean, G. Thurston, S. Roberge, R.K. Jain, and D.M. McDonald Openings between defective endothelial cells explain tumor vessel leakiness Am. J. Pathol. 156 2000 1363 1380
105. C.H. Heldin, K. Rubin, K. Pietras, and A. Ostman High interstitial fluid pressure-an obstacle in cancer therapy Nat. Rev. Cancer 4 2004 806 813
106. J.A. Nagy, S.H. Chang, A.M. Dvorak, and H.F. Dvorak Why are tumour blood vessels abnormal and why is it important to know? Brit. J. Cancer 100 2009 865 869