Purpose. The following review focuses on the recent advancements in intravesical drug delivery, which brings added benefit to the therapy of detrusor overactivity and interstitial cystitis/painful bladder syndrome (IC/PBS). Results. Intravesical route is a preferred route of administration for restricting the action of extremely potent drugs like DMSO for patients of interstitial cystitis/painful bladder syndrome (IC/PBS) and botulinum toxin for detrusor overactivity. Patients who are either refractory to oral treatment or need to mitigate the adverse effects encountered with conventional routes of administration also chose this route. Its usefulness in some cases can be limited by vehicle (carrier) toxicity or short duration of action. Efforts have been underway to overcome these limitations by developing liposome platform for intravesical delivery of biotechnological products including antisense oligonucleotides. Conclusions. Adoption of forward-thinking approaches can achieve advancements in drug delivery systems targeted to future improvement in pharmacotherapy of bladder diseases. Latest developments in the field of nanotechnology can bring this mode of therapy from second line of treatment for refractory cases to the forefront of disease management. 1. Introduction Intravesical therapies have demonstrated varying degrees of efficacy and safety in treatment of interstitial cystitis/painful bladder syndrome (IC/PBS) [1] and overactive bladder OAB [2]. Pharmacotherapy by this route provides high local drug concentrations in the bladder with low risk of systemic side effects [3]. Conventional therapies for OAB and detrusor overactivity (DO), either neurogenic or idiopathic, have limited efficacy and acceptability. Anticholinergic medications, which are currently the mainstay of the treatment of OAB, are not always effective and often have undesirable side effects such as dry mouth and constipation [4]. Therefore, search for alternative therapies directed against local targets with fewer side effects is encouraged. The IC/PBS syndrome is characterized by pelvic pain and urinary storage symptoms (e.g., urinary urgency and frequency). The O’Leary-Sant symptom and problem score (interstitial cystitis symptom index (ICSI) and problem index (ICPI)) is recognized as one of the most reliable and valid instruments to identify the extent of bothersome symptoms and the most prominent voiding and painful symptoms in IC/PBS patients [5, 6]. Pentosan polysulfate, PPS, is a synthetic sulphated polysaccharide and is the only approved oral drug for IC/PBS, but it
References
[1]
J. Parkin, C. Shea, and G. R. Sant, “Intravesical dimethyl sulfoxide (DMSO) for interstitial cystitis—a practical approach,” Urology, vol. 49, no. 5, pp. 105–107, 1997.
[2]
C. Dowson, J. Watkins, M. S. Khan, P. Dasgupta, and A. Sahai, “Repeated botulinum toxin type A injections for refractory overactive bladder: medium-term outcomes, safety profile, and discontinuation rates,” European Urology, vol. 61, no. 4, pp. 834–839, 2012.
[3]
J. Kaufman, V. Tyagi, M. Anthony, M. B. Chancellor, and P. Tyagi, “State of the art in intravesical therapy for lower urinary tract symptoms,” Reviews in Urology, vol. 12, pp. e181–e189, 2010.
[4]
N. Yoshimura and M. B. Chancellor, “Current and future pharmacological treatment for overactive bladder,” Journal of Urology, vol. 168, no. 5, pp. 1897–1913, 2002.
[5]
K. A. Killinger, J. A. Boura, and K. M. Peters, “Pain in interstitial cystitis/bladder pain syndrome: do characteristics differ in ulcerative and non-ulcerative subtypes?” International Urogynecology Journal, vol. 24, no. 8, pp. 1295–1301, 2013.
[6]
J. C. Nickel, P. Hanno, K. Kumar, and H. Thomas, “Second multicenter, randomized, double-blind, parallel-group evaluation of effectiveness and safety of intravesical sodium chondroitin sulfate compared with inactive vehicle control in subjects with interstitial cystitis/bladder pain syndrome,” Urology, vol. 79, no. 6, pp. 1220–1225, 2012.
[7]
P. M. Hanno, “Analysis of long-term elmiron therapy for interstitial cystitis,” Urology, vol. 49, no. 5, pp. 93–99, 1997.
[8]
A. Giannantoni, V. Bini, R. Dmochowski et al., “Reply to Claus Riedl's letter to the editor re: antonella Giannantoni, Vittorio Bini, Roger Dmochowski, et al. Contemporary management of the painful bladder: a systematic review,” European Urology, vol. 61, no. 5, pp. 29–53, 2012.
[9]
M. C. Lai, Y. C. Kuo, and H. C. Kuo, “Intravesical hyaluronic acid for interstitial cystitis/painful bladder syndrome: a comparative randomized assessment of different regimens,” International Journal of Urology, vol. 20, pp. 203–207, 2013.
[10]
J. Eldrup, J. Thorup, and S. L. Nielsen, “Permeability and ultrastructure of human bladder epithelium,” British Journal of Urology, vol. 55, no. 5, pp. 488–492, 1983.
[11]
C. L. Parsons, D. Boychuk, S. Jones, R. Hurst, and H. Callahan, “Bladder surface glycosaminoglycans: an epithelial permeability barrier,” Journal of Urology, vol. 143, no. 1, pp. 139–142, 1990.
[12]
Y. Kim, N. Yoshimura, H. Masuda, F. De Miguel, and M. B. Chancellor, “Antimuscarinic agents exhibit local inhibitory effects on muscarinic receptors in bladder-afferent pathways,” Urology, vol. 65, no. 2, pp. 238–242, 2005.
[13]
V. Tyagi, B. J. Philips, R. Su et al., “Differential expression of functional cannabinoid receptors in human bladder detrusor and urothelium,” Journal of Urology, vol. 181, no. 4, pp. 1932–1938, 2009.
[14]
B. J. Philips, M. C. Smaldone, V. L. Erickson, N. Yoshimura, M. B. Chancellor, and P. Tyagi, “Differential expression of neurokinin receptor subtypes in urothelium and detrusor of human bladder,” Journal of Urology, vol. 179, article 354, 2008.
[15]
S. A. Baker, G. W. Hennig, J. Han, F. C. Britton, T. K. Smith, and S. D. Koh, “Methionine and its derivatives increase bladder excitability by inhibiting stretch-dependent K+ channels,” British Journal of Pharmacology, vol. 153, no. 6, pp. 1259–1271, 2008.
[16]
J. M. Beckel, A. Kanai, S.-J. Lee, W. C. De Groat, and L. A. Birder, “Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells,” American Journal of Physiology—Renal Physiology, vol. 290, no. 1, pp. F103–F110, 2006.
[17]
L. A. Birder, A. J. Kanai, W. C. De Groat et al., “Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 23, pp. 13396–13401, 2001.
[18]
P. Tyagi, C. A. Thomas, N. Yoshimura, and M. B. Chancellor, “Investigations into the presence of functional ?1, ?2 and ?3-adrenoceptors in urothelium and detrusor of human bladder,” International Brazilian Journal of Urology, vol. 35, no. 1, pp. 76–83, 2009.
[19]
A. T. Hanna-Mitchell, J. M. Beckel, S. Barbadora, A. J. Kanai, W. C. de Groat, and L. A. Birder, “Non-neuronal acetylcholine and urinary bladder urothelium,” Life Sciences, vol. 80, no. 24-25, pp. 2298–2302, 2007.
[20]
C. P. Smith, D. A. Gangitano, A. Munoz et al., “Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury,” Neurochemistry International, vol. 52, no. 6, pp. 1068–1075, 2008.
[21]
Y.-C. Chuang, C. A. Thomas, S. Tyagi, N. Yoshimura, P. Tyagi, and M. B. Chancellor, “Human urine with solifenacin intake but not tolterodine or darifenacin intake blocks detrusor overactivity,” International Urogynecology Journal and Pelvic Floor Dysfunction, vol. 19, no. 10, pp. 1353–1357, 2008.
[22]
Y. Kim, N. Yoshimura, H. Masuda, F. D. Miguel, and M. B. Chancellor, “Intravesical instillation of human urine after oral administration of trospium, tolterodine and oxybutynin in a rat model of detrusor overactivity,” BJU International, vol. 97, no. 2, pp. 400–403, 2006.
[23]
S. Tyagi, P. Tyagi, S. Van-le, N. Yoshimura, M. B. Chancellor, and F. de Miguel, “Qualitative and quantitative expression profile of muscarinic receptors in human urothelium and detrusor,” Journal of Urology, vol. 176, no. 4, pp. 1673–1678, 2006.
[24]
G. Gregoriadis and B. E. Ryman, “Liposomes as carriers of enzymes or drugs: a new approach to the treatment of storage diseases,” Biochemical Journal, vol. 124, no. 5, p. 58, 1971.
[25]
G. Gregoriadis, S. Jain, I. Papaioannou, and P. Laing, “Improving the therapeutic efficacy of peptides and proteins: a role for polysialic acids,” International Journal of Pharmaceutics, vol. 300, no. 1-2, pp. 125–130, 2005.
[26]
P. Sapra, P. Tyagi, and T. M. Allen, “Ligand-targeted liposomes for cancer treatment,” Current Drug Delivery, vol. 2, no. 4, pp. 369–381, 2005.
[27]
G. Gregoriadis, G. Dapergolas, and E. D. Neerunjun, “Penetration of target areas in the rat by liposome associated agents administered parenterally and intragastrically,” Biochemical Society Transactions, vol. 4, no. 2, pp. 256–259, 1976.
[28]
G. Gregoriadis, “Engineering liposomes for drug delivery: progress and problems,” Trends in Biotechnology, vol. 13, no. 12, pp. 527–537, 1995.
[29]
G. Gregoriadis and A. C. Allison, “Entrapment of proteins in liposomes prevents allergic reactions in pre immunised mice,” FEBS Letters, vol. 45, no. 1, pp. 71–74, 1974.
[30]
S. Lee, S. Dausch, C. Maierhofer, and D. Dausch, “A new therapy concept with a liposome eye spray for the treatment of the ‘dry eye’,” Klinische Monatsblatter fur Augenheilkunde, vol. 221, no. 10, pp. 825–836, 2004.
[31]
D. Dausch, S. Lee, S. Dausch, J. C. Kim, G. Schwert, and W. Michelson, “Comparative study of treatment of the dry eye syndrome due to disturbances of the tear film lipid layer with lipid-containing tear substitutes: efficacy of lipid-containing tear substitutes,” Klinische Monatsblatter fur Augenheilkunde, vol. 223, no. 12, pp. 974–983, 2006.
[32]
S. Ebrahim, G. A. Peyman, and P. J. Lee, “Applications of liposomes in ophthalmology,” Survey of Ophthalmology, vol. 50, no. 2, pp. 167–182, 2005.
[33]
J. Nirmal, P. Tyagi, L. Dang et al., “Endocytosis uptake of liposomes in urothelium cells detected by transmission electron microscopy,” The Journal of Urology, vol. 187, article e15, 2012.
[34]
D. N. Frangos, J. J. Killion, D. Fan, R. Fishbeck, A. C. Von Eschenbach, and I. J. Fidler, “The development of liposomes containing interferon alpha for the intravesical therapy of human superficial bladder cancer,” Journal of Urology, vol. 143, no. 6, pp. 1252–1266, 1990.
[35]
J. W. Johnson, R. Nayar, J. J. Killion, A. C. Von Eschenbach, and I. J. Fidler, “Binding of liposomes to human bladder tumor epithelial cell lines: implications for an intravesical drug delivery system for the treatment of bladder cancer,” Selective Cancer Therapeutics, vol. 5, no. 4, pp. 147–155, 1989.
[36]
Y.-C. Chuang, M. B. Chancellor, S. Seki et al., “Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity,” Urology, vol. 61, no. 3, pp. 664–670, 2003.
[37]
J. Kaufman, P. Tyagi, and M. B. Chancellor, “Intravesical liposomal (Lp08) instillation protects bladder urothelium from chemical irritation,” The Journal of Urology, vol. 181, article 539, 2009.
[38]
P. Tyagi, M. B. Chancellor, Z. Li et al., “Urodynamic and immunohistochemical evaluation of intravesical capsaicin delivery using thermosensitive hydrogel and liposomes,” Journal of Urology, vol. 171, no. 1, pp. 483–489, 2004.
[39]
M. O. Fraser, Y.-C. Chuang, P. Tyagi et al., “Intravesical liposome administration—a novel treatment for hyperactive bladder in the rat,” Urology, vol. 61, no. 3, pp. 656–663, 2003.
[40]
P. Tyagi, M. Chancellor, N. Yoshimura, and L. Huang, “Activity of different phospholipids in attenuating hyperactivity in bladder irritation,” BJU International, vol. 101, no. 5, pp. 627–632, 2008.
[41]
Y. Sun and T. C. Chai, “Effects of dimethyl sulphoxide and heparin on stretch-activated ATP release by bladder urothelial cells from patients with interstitial cystitis,” BJU International, vol. 90, no. 4, pp. 381–385, 2002.
[42]
J. J. Bade, “A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis,” British Journal of Urology, vol. 79, no. 2, pp. 168–171, 1997.
[43]
P. Tyagi, V. C. Hsieh, N. Yoshimura, J. Kaufman, and M. B. Chancellor, “Instillation of liposomes vs dimethyl sulphoxide or pentosan polysulphate for reducing bladder hyperactivity,” BJU International, vol. 104, no. 11, pp. 1689–1692, 2009.
[44]
W.-C. Lee, C.-T. Chien, H.-J. Yu, and S.-W. Lee, “Bladder dysfunction in rats with metabolic syndrome induced by long-term fructose feeding,” Journal of Urology, vol. 179, no. 6, pp. 2470–2476, 2008.
[45]
J. I. Gillespie, G. A. Van Koeveringe, S. G. De Wachter, and J. De Vente, “On the origins of the sensory output from the bladder: the concept of afferent noise,” BJU International, vol. 103, no. 10, pp. 1324–1333, 2009.
[46]
W. C. Lee, P. H. Chiang, Y. L. Tain, C. C. Wu, and Y. C. Chuang, “Sensory dysfunction of bladder mucosa and bladder oversensitivity in a rat model of metabolic syndrome,” PloS ONE, vol. 7, Article ID e45578, 2012.
[47]
Y.-C. Chuang, W.-C. Lee, W.-C. Lee, and P.-H. Chiang, “Intravesical liposome versus oral pentosan polysulfate for interstitial cystitis/painful bladder syndrome,” Journal of Urology, vol. 182, no. 4, pp. 1393–1400, 2009.
[48]
W.-C. Lee, Y.-C. Chuang, W.-C. Lee, and P.-H. Chiang, “Safety and dose flexibility clinical evaluation of intravesical liposome in patients with interstitial cystitis or painful bladder syndrome,” Kaohsiung Journal of Medical Sciences, vol. 27, no. 10, pp. 437–440, 2011.
[49]
S. T. Truschel, E. Wang, W. G. Ruiz et al., “Stretch-regulated exocytosis/endocytosis in bladder umbrella cells,” Molecular Biology of the Cell, vol. 13, no. 3, pp. 830–846, 2002.
[50]
M. B. Chancellor and W. C. De Groat, “Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder,” Journal of Urology, vol. 162, no. 1, pp. 3–11, 1999.
[51]
D. S. Byrne, A. Das, J. Sedor et al., “Effect of intravesical capsaicin and vehicle on bladder integrity in control and spinal cord injured rats,” Journal of Urology, vol. 159, no. 3, pp. 1074–1078, 1998.
[52]
M. Mandal and K.-D. Lee, “Listeriolysin O-liposome-mediated cytosolic delivery of macromolecule antigen in vivo: enhancement of antigen-specific cytotoxic T lymphocyte frequency, activity, and tumor protection,” Biochimica et Biophysica Acta, vol. 1563, no. 1-2, pp. 7–17, 2002.
[53]
Y.-C. Chuang, P. Tyagi, C.-C. Huang et al., “Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin a delivery using liposomes,” Journal of Urology, vol. 182, no. 2, pp. 786–792, 2009.
[54]
Y.-C. Chuang, N. Yoshimura, C.-C. Huang, P.-H. Chiang, and M. B. Chancellor, “Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats,” Journal of Urology, vol. 172, no. 4, pp. 1529–1532, 2004.
[55]
S. P. Petrou, A. S. Parker, J. E. Crook, A. Rogers, D. Metz-Kudashick, and D. D. Thiel, “Botulinum A toxin/dimethyl sulfoxide bladder instillations for women with refractory idiopathic detrusor overactivity: a phase 1/2 study,” Mayo Clinic Proceedings, vol. 84, no. 8, pp. 702–706, 2009.
[56]
P. Caccin, O. Rossetto, M. Rigoni, E. Johnson, G. Schiavo, and C. Montecucco, “VAMP/synaptobrevin cleavage by tetanus and botulinum neurotoxins is strongly enhanced by acidic liposomes,” FEBS Letters, vol. 542, no. 1–3, pp. 132–136, 2003.
[57]
M. L. Stephenson and P. C. Zamecnik, “Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 75, no. 1, pp. 285–288, 1978.
[58]
H. Dadgostar and N. Waheed, “The evolving role of vascular endothelial growth factor inhibitors in the treatment of neovascular age-related macular degeneration,” Eye, vol. 22, no. 6, pp. 761–767, 2008.
[59]
C. Gebhard, G. Huard, E. A. Kritikou, and J. C. Tardif, “Apolipoprotein B antisense inhibition—update on mipomersen,” Current Pharmaceutical Design, vol. 919, no. 17, pp. 3132–3142, 2013.
[60]
T. Yokota, E. Hoffman, and S. Takeda, “Antisense oligo-mediated multiple exon skipping in a dog model of duchenne muscular dystrophy,” Methods in Molecular Biology, vol. 709, pp. 299–312, 2011.
[61]
B. L. Jacobs, M. C. Smaldone, V. Tyagi et al., “Increased nerve growth factor in neurogenic overactive bladder and interstitial cystitis patients,” The Canadian Journal of Urology, vol. 17, no. 1, pp. 4989–4994, 2010.
[62]
H.-T. Liu and H.-C. Kuo, “Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis,” Urology, vol. 70, no. 3, pp. 463–468, 2007.
[63]
H. T. Liu and H. C. Kuo, “Increased urine and serum nerve growth factor levels in interstitial cystitis suggest chronic inflammation is involved in the pathogenesis of disease,” PloS ONE, vol. 7, Article ID e44687, 2012.
[64]
N. Yoshimura, N. E. Bennett, Y. Hayashi et al., “Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats,” Journal of Neuroscience, vol. 26, no. 42, pp. 10847–10855, 2006.
[65]
S. Seki, K. Sasaki, Y. Igawa et al., “Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats,” Journal of Urology, vol. 171, no. 1, pp. 478–482, 2004.
[66]
R. J. Evans, R. M. Moldwin, N. Cossons, A. Darekar, I. W. Mills, and D. Scholfield, “Proof of concept trial of tanezumab for the treatment of symptoms associated with interstitial cystitis,” Journal of Urology, vol. 185, no. 5, pp. 1716–1721, 2011.
[67]
P. Tyagi, R. Banerjee, S. Basu, N. Yoshimura, M. Chancellor, and L. Huang, “Intravesical antisense therapy for cystitis using TAT-peptide nucleic acid conjugates,” Molecular Pharmaceutics, vol. 3, no. 4, pp. 398–406, 2006.
[68]
D. C. Molliver, D. E. Wright, M. L. Leitner et al., “IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life,” Neuron, vol. 19, no. 4, pp. 849–861, 1997.
[69]
M. Tyagi, M. Rusnati, M. Presta, and M. Giacca, “Internalization of HIV-1 tat requires cell surface heparan sulfate proteoglycans,” Journal of Biological Chemistry, vol. 276, no. 5, pp. 3254–3261, 2001.
[70]
E. Uhlmann, A. Ryte, and A. Peyman, “Studies on the mechanism of stabilization of partially phosphorothioated oligonucleotides against nucleolytic degradation,” Antisense and Nucleic Acid Drug Development, vol. 7, no. 4, pp. 345–350, 1997.
[71]
M. Nogawa, T. Yuasa, S. Kimura et al., “Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer,” Journal of Clinical Investigation, vol. 115, no. 4, pp. 978–985, 2005.
[72]
M. Kashyap, N. Kawamorita, V. Tyagi et al., “Downregulation of NGF expression in the bladder by antisense oligoucleotides as new treatment for overactive bladder,” Journal of Urology, vol. 27190, no. 2, pp. 757–764, 2013.
[73]
C.-J. Arum, Y. Kodama, N. Rolim et al., “A rat model of intravesical delivery of small interfering RNA for studying urinary carcinoma,” World Journal of Urology, vol. 28, no. 4, pp. 479–485, 2010.
[74]
C. E. Blietz, B. Thode, M. Hauses et al., “In vivo studies on the availability and toxicity of antisense oligonucleotides in bladder cancer,” In Vivo, vol. 23, no. 1, pp. 13–19, 2009.
[75]
D. Oddiah, P. Anand, S. B. McMahon, and M. Rattray, “Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder,” NeuroReport, vol. 9, no. 7, pp. 1455–1458, 1998.
[76]
M. R. Saban, H. Hellmich, N. B. Nguyen, J. Winston, T. G. Hammond, and R. Saban, “Time course of LPS-induced gene expression in a mouse model of genitourinary inflammation,” Physiol Genomics, vol. 5, no. 3, pp. 147–160, 2001.
[77]
B. Schnegelsberg, T. T. Sun, G. Cain et al., “Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function,” The American Journal of Physiology—Regulatory, Integrative and Comparative Physiology, vol. 298, no. 5, pp. R534–R547, 2010.
[78]
S. Cardenas, M. Scuri, L. Samsell et al., “Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs,” American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 299, no. 3, pp. L334–L344, 2010.
[79]
K. Nakamura, F. Tan, Z. Li, and C. J. Thiele, “NGF activation of TrkA induces vascular endothelial growth factor expression via induction of hypoxia-inducible factor-1α,” Molecular and Cellular Neuroscience, vol. 46, no. 2, pp. 498–506, 2011.
[80]
S. Othumpangat, M. Regier, and G. Piedimonte, “Nerve growth factor modulates human rhinovirus infection in airway epithelial cells by controlling ICAM-1 expression,” American Journal of Physiology Lung Cellular and Molecular Physiology, vol. 15302, pp. L1057–L1066, 2012.
[81]
H. Jung, P. T. Toth, F. A. White, and R. J. Miller, “Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons,” Journal of Neurochemistry, vol. 104, no. 1, pp. 254–263, 2008.
[82]
F. A. White, H. Jung, and R. J. Miller, “Chemokines and the pathophysiology of neuropathic pain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 51, pp. 20151–20158, 2007.
[83]
G. Banisadr, R.-D. Gosselin, P. Mechighel, W. Rostène, P. Kitabgi, and S. M. Parsadaniantz, “Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: functional effect of MCP-1/CCL2 on calcium mobilization in primary cultured neurons,” Journal of Comparative Neurology, vol. 492, no. 2, pp. 178–192, 2005.
[84]
S. Bhangoo, D. Ren, R. J. Miller et al., “Delayed functional expression of neuronal chemokine receptors following focal nerve demyelination in the rat: a mechanism for the development of chronic sensitization of peripheral nociceptors,” Molecular Pain, vol. 3, article 38, 2007.
[85]
T. Maeda, N. Kiguchi, Y. Kobayashi, T. Ikuta, M. Ozaki, and S. Kishioka, “Leptin derived from adipocytes in injured peripheral nerves facilitates development of neuropathic pain via macrophage stimulation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 31, pp. 13076–13081, 2009.
[86]
H. Kajiwara, M. Yasuda, N. Kumaki, T. Shibayama, and Y. Osamura, “Expression of carbohydrate antigens (SSEA-1, Sialyl-Lewis X, DU-PAN-2 and CA19-9) and E-selectin in urothelial carcinoma of the renal pelvis, ureter, and urinary bladder,” Tokai Journal of Experimental and Clinical Medicine, vol. 30, no. 3, pp. 177–182, 2005.
[87]
A. M. S. Assreuy, G. J. Martins, M. E. F. Moreira et al., “Prevention of cyclophosphamide-induced hemorrhagic cystitis by glucose- mannose binding plant lectins,” Journal of Urology, vol. 161, no. 6, pp. 1988–1993, 1999.
[88]
S. M. Vinson, A. Rickard, J. S. Ryerse, and J. McHowat, “Neutrophil adherence to bladder microvascular endothelial cells following platelet-activating factor acetylhydrolase inhibition,” Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 3, pp. 1241–1247, 2005.
[89]
M. Green, A. Filippou, G. Sant, and T. C. Theoharides, “Expression of intercellular adhesion molecules in the bladder of patients with interstitial cystitis,” Urology, vol. 63, no. 4, pp. 688–693, 2004.
[90]
M. Leppilahti, P. Hellstr?m, and T. L. J. Tammela, “Effect of diagnostic hydrodistension and four intravesical hyaluronic acid instillations on bladder ICAM-1 intensity and association of ICAM-1 intensity with clinical response in patients with interstitial cystitis,” Urology, vol. 60, no. 1, pp. 46–51, 2002.
[91]
A. T. Corcoran, N. Yoshimura, V. Tyagi, B. Jacobs, W. Leng, and P. Tyagi, “Mapping the cytokine profile of painful bladder syndrome/interstitial cystitis in human bladder and urine specimens,” World Journal of Urology, vol. 31, no. 1, pp. 241–246, 2013.
[92]
S. Garrean, X.-P. Gao, V. Brovkovych et al., “Caveolin-1 regulates NF-κB activation and lung inflammatory response to sepsis induced by lipopolysaccharide,” Journal of Immunology, vol. 177, no. 7, pp. 4853–4860, 2006.
[93]
M. R. Kang, G. Yang, R. F. Place et al., “Intravesical delivery of small activating RNA formulated into lipid nanoparticles inhibits orthotopic bladder tumor growth,” Cancer Research, vol. 172, pp. 5069–5079, 2012.
[94]
P. Tyagi, D. Barclay, R. Zamora et al., “Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study,” International Urology and Nephrology, vol. 42, no. 3, pp. 629–635, 2010.
[95]
P. Tyagi, B. L. Jacobs, D. Barcaly et al., “Urine levels of inflammatory chemokines can be novel biomarkers for the overactive bladder,” The Journal of Urology, vol. 181, article 588, 2009.
[96]
P. Tyagi, V. Tyagi, D. Bui et al., “Discrimination Of OAB from IC/PBS by multivariate data modeling of urinary proteins,” The Journal of Urology, vol. 183, pp. e614–e6e5, 2010.
[97]
P. Tyagi, D. Nikolavsky, Y. Vodovotz et al., “Urine levels of selected chemokines positively correlate with lower bladder capacity and psychometric scores in Ic/Pbs patients,” The Journal of Urology, vol. 181, article 21, 2009.
[98]
R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nature Medicine, vol. 9, no. 1, pp. 123–128, 2003.
[99]
C. Bremer, V. Ntziachristos, and R. Weissleder, “Optical-based molecular imaging: contrast agents and potential medical applications,” European Radiology, vol. 13, no. 2, pp. 231–243, 2003.
[100]
U. Mahmood and R. Weissleder, “Near-infrared optical imaging of proteases in cancer,” Molecular Cancer Therapeutics, vol. 2, pp. 489–496, 2003.
[101]
J. Kaufman, H. Hensley, J. Jacobs et al., “Non-invasive imaging of near infrafred dye labeled liposomes facilitates evaluation of bioresidence time,” The Journal of Urology, vol. 183, article e628, 2010.
[102]
Y.-X. J. Wang, “Medical imaging in pharmaceutical clinical trials: what radiologists should know,” Clinical Radiology, vol. 60, no. 10, pp. 1051–1057, 2005.