Intranasal Radioiodinated Ferulic Acid Polymeric Micelles as the First
Nuclear Medicine Imaging Probe for ETRA Brain Receptor

Hend      Fayez; Adli      Selim; Rehab      Shamma; Hassan      Rashed
doi:10.2174/0118744710269885231113070356
Abstract

Introduction: The aim of this work was to prepare a selective nuclear medicine imaging probe for the Endothelin 1 receptor A in the brain.
Material and Methods: Ferulic acid (an ETRA antagonist) was radiolabeled using ¹³¹I by direct electrophilic substitution method. The radiolabeled ferulic acid was formulated as polymeric micelles to allow intranasal brain delivery. Biodistribution was studied in Swiss albino mice by comparing brain uptake of ¹³¹I-ferulic acid after IN administration of ¹³¹I-ferulic acid polymeric micelles, IN administration of ¹³¹I-ferulic acid solution and IV administration of ¹³¹I-ferulic acid solution.
Results: Successful radiolabeling was achieved with an RCY of 98 % using 200 μg of ferulic acid and 60 μg of CAT as oxidizing agents at pH 6, room temperature and 30 min reaction time. ¹³¹I-ferulic acid polymeric micelles were successfully formulated with the particle size of 21.63 nm and polydispersity index of 0.168. Radioactivity uptake in the brain and brain/blood uptake ratio for I.N ¹³¹I-ferulic acid polymeric micelles were greater than the two other routes at all periods.
Conclusion: Our results provide ¹³¹I-ferulic acid polymeric micelles as a hopeful nuclear medicine tracer for ETRA brain receptor.
« Previous
Graphical Abstract

[1]
Wong, D.F.; Gründer, G.; Brašić, J.R. Brain imaging research: Does the science serve clinical practice? Int. Rev. Psychiatry,  2007, 19(5), 541-558.
 [http://dx.doi.org/10.1080/09540260701564849] [PMID: 17896234]

[2]
Heiss, W-D.; Herholz, K. Brain receptor imaging. J. Nucl. Med.,  2006, 47(2), 302-312.
 [PMID: 16455637]

[3]
Herfert, K.; Mannheim, J.G.; Kuebler, L.; Marciano, S.; Amend, M.; Parl, C.; Napieczynska, H.; Maier, F.M.; Vega, S.C.; Pichler, B.J. Quantitative rodent brain receptor imaging. Mol. Imaging Biol.,  2020, 22(2), 223-244.
 [http://dx.doi.org/10.1007/s11307-019-01368-9] [PMID: 31168682]

[4]
Meredith, G.E. The synaptic framework for chemical signaling in nucleus accumbens. Ann. N. Y. Acad. Sci.,  1999, 877(1), 140-156.
 [http://dx.doi.org/10.1111/j.1749-6632.1999.tb09266.x] [PMID: 10415648]

[5]
Lauder, J.M. Neurotransmitters as growth regulatory signals: Role of receptors and second messengers. Trends Neurosci.,  1993, 16(6), 233-240.
 [http://dx.doi.org/10.1016/0166-2236(93)90162-F] [PMID: 7688165]

[6]
van Waarde, A.; Dierckx, R.A.J.O.; Zhou, X.; Khanapur, S.; Tsukada, H.; Ishiwata, K.; Luurtsema, G.; de Vries, E.F.J.; Elsinga, P.H. Potential therapeutic applications of adenosine A2A receptor ligands and opportunities for A2A receptor imaging. Med. Res. Rev.,  2018, 38(1), 5-56.
 [http://dx.doi.org/10.1002/med.21432] [PMID: 28128443]

[7]
Frost, J.J. Receptor imaging by PET and SPECT: Focus on the opiate receptor. J. Recept. Res.,  1993, 13(1-4), 39-53.
 [http://dx.doi.org/10.3109/10799899309073644] [PMID: 8095556]

[8]
Fleuriet, A.; Macheix, J.-J. Phenolic acids in fruits and vegetables;; Oxidative stress and disease, 2003, 9, pp. 1-42.

[9]
Boz, H. Ferulic acid in cereals-a review. Czech J. Food Sci.,  2015, 33(1), 1-7.
 [http://dx.doi.org/10.17221/401/2014-CJFS]

[10]
Huang, W.Y.; Cai, Y.Z.; Zhang, Y. Natural phenolic compounds from medicinal herbs and dietary plants: Potential use for cancer prevention. Nutr. Cancer,  2009, 62(1), 1-20.
 [http://dx.doi.org/10.1080/01635580903191585] [PMID: 20043255]

[11]
Srinivasan, M.; Sudheer, A.R.; Menon, V.P. Ferulic Acid: Therapeutic potential through its antioxidant property. J. Clin. Biochem. Nutr.,  2007, 40(2), 92-100.
 [http://dx.doi.org/10.3164/jcbn.40.92] [PMID: 18188410]

[12]
Yan, H.; Meng, X.; Lin, X.; Duan, N.; Wang, Z.; Wu, S. Antifungal activity and inhibitory mechanisms of ferulic acid against the growth of Fusarium graminearum. Food Biosci.,  2023, 52, 102414.
 [http://dx.doi.org/10.1016/j.fbio.2023.102414]

[13]
Graf, E. Antioxidant potential of ferulic acid. Free Radic. Biol. Med.,  1992, 13(4), 435-448.
 [http://dx.doi.org/10.1016/0891-5849(92)90184-I] [PMID: 1398220]

[14]
Li, W.; Li, N.; Tang, Y.; Li, B.; Liu, L.; Zhang, X.; Fu, H.; Duan, J. Biological activity evaluation and structure–activity relationships analysis of ferulic acid and caffeic acid derivatives for anticancer. Bioorg. Med. Chem. Lett.,  2012, 22(19), 6085-6088.
 [http://dx.doi.org/10.1016/j.bmcl.2012.08.038] [PMID: 22954735]

[15]
Eroğlu, C.; Seçme, M.; Bağcı, G.; Dodurga, Y. Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines. Tumour Biol.,  2015, 36(12), 9437-9446.
 [http://dx.doi.org/10.1007/s13277-015-3689-3] [PMID: 26124008]

[16]
Li, D.; Rui, Y.; Guo, S.; Luan, F.; Liu, R.; Zeng, N. Ferulic acid: A review of its pharmacology, pharmacokinetics and derivatives. Life Sci.,  2021, 284, 119921.
 [http://dx.doi.org/10.1016/j.lfs.2021.119921] [PMID: 34481866]

[17]
Zhang, X-X.; Zhao, D.S.; Wang, J.; Zhou, H.; Wang, L.; Mao, J.L.; He, J.X. The treatment of cardiovascular diseases: A review of ferulic acid and its derivatives. Pharmazie,  2021, 76(2), 55-60.
 [PMID: 33714280]

[18]
Dasgupta, F.; Mukherjee, A.; Gangadhar, N. Endothelin receptor antagonists-an overview. Curr. Med. Chem.,  2002, 9(5), 549-575.
 [http://dx.doi.org/10.2174/0929867024606966] [PMID: 11945124]

[19]
Leng, N.; Gu, G.; Simerly, R.B.; Spindel, E.R. Molecular cloning and characterization of two putative G protein-coupled receptors which are highly expressed in the central nervous system. Brain Res. Mol. Brain Res.,  1999, 69(1), 73-83.
 [http://dx.doi.org/10.1016/S0169-328X(99)00092-3] [PMID: 10350639]

[20]
Davenport, A.P.; Hyndman, K.A.; Dhaun, N.; Southan, C.; Kohan, D.E.; Pollock, J.S.; Pollock, D.M.; Webb, D.J.; Maguire, J.J. Endothelin. Pharmacol. Rev.,  2016, 68(2), 357-418.
 [http://dx.doi.org/10.1124/pr.115.011833] [PMID: 26956245]

[21]
Pearson, J.D. Normal endothelial cell function. Lupus,  2000, 9(3), 183-188.
 [http://dx.doi.org/10.1191/096120300678828299] [PMID: 10805485]

[22]
Barone, F.C.; Willette, R.N.; Yue, T.L.; Feurestein, G. Therapeutic effects of endothelin receptor antagonists in stroke. Neurol. Res.,  1995, 17(4), 259-264.
 [http://dx.doi.org/10.1080/01616412.1995.11740323] [PMID: 7477739]

[23]
Sato, M.; Noble, L.J. Involvement of the endothelin receptor subtype A in neuronal pathogenesis after traumatic brain injury. Brain Res.,  1998, 809(1), 39-49.
 [http://dx.doi.org/10.1016/S0006-8993(98)00817-8] [PMID: 9795123]

[24]
Pla, P.; Larue, L. Involvement of endothelin receptors in normal and pathological development of neural crest cells. Int. J. Dev. Biol.,  2003, 47(5), 315-325.
 [PMID: 12895026]

[25]
Mariani, G.; Bruselli, L.; Kuwert, T.; Kim, E.E.; Flotats, A.; Israel, O.; Dondi, M.; Watanabe, N. A review on the clinical uses of SPECT/CT. Eur. J. Nucl. Med. Mol. Imaging,  2010, 37(10), 1959-1985.
 [http://dx.doi.org/10.1007/s00259-010-1390-8] [PMID: 20182712]

[26]
Kaasinen, V.; Vahlberg, T.; Stoessl, A.J.; Strafella, A.P.; Antonini, A. Dopamine receptors in Parkinson’s disease: A meta‐analysis of imaging studies. Mov. Disord.,  2021, 36(8), 1781-1791.
 [http://dx.doi.org/10.1002/mds.28632] [PMID: 33955044]

[27]
Anzola, L.K.; Glaudemans, A.W.J.M.; Dierckx, R.A.J.O.; Martinez, F.A.; Moreno, S.; Signore, A. Somatostatin receptor imaging by SPECT and PET in patients with chronic inflammatory disorders: A systematic review. Eur. J. Nucl. Med. Mol. Imaging,  2019, 46(12), 2496-2513.
 [http://dx.doi.org/10.1007/s00259-019-04489-z] [PMID: 31463594]

[28]
Sakr, T.; Khedr, M.; Rashed, H.; Mohamed, M. In silico-based repositioning of phosphinothricin as a novel technetium-99m imaging probe with potential anti-cancer activity. Molecules,  2018, 23(2), 496.
 [http://dx.doi.org/10.3390/molecules23020496] [PMID: 29473879]

[29]
Ramezani Farani, M.; Aminzadeh Jahromi, N.; Ali, V.; Ebrahimpour, A.; Salehian, E.; Shafiee Ardestani, M.; Seyedhamzeh, M.; Ahmadi, S.; Sharifi, E.; Ashrafizadeh, M.; Rabiee, N.; Makvandi, P. Detection of dopamine receptors using nanoscale dendrimer for potential application in targeted delivery and whole-body imaging: Synthesis and in vivo organ distribution. ACS Appl. Bio Mater.,  2022, 5(4), 1744-1755.
 [http://dx.doi.org/10.1021/acsabm.2c00118] [PMID: 35377588]

[30]
Pain, C.D.; O’Keefe, G.J.; Ackermann, U.; Dore, V.; Villemagne, V.L.; Rowe, C.C. Human biodistribution and internal dosimetry of 4-[18F]fluorobenzyl-dexetimide: a PET radiopharmaceutical for imaging muscarinic acetylcholine receptors in the brain and heart. EJNMMI Res.,  2020, 10(1), 61.
 [http://dx.doi.org/10.1186/s13550-020-00641-1] [PMID: 32533449]

[31]
Rashed, H.M.; Marzook, F.A.; Farag, H. 99mTc-zolmitriptan: Radiolabeling, molecular modeling, biodistribution and gamma scintigraphy as a hopeful radiopharmaceutical for lung nuclear imaging. Radiol. Med.,  2016, 121(12), 935-943.
 [http://dx.doi.org/10.1007/s11547-016-0677-7] [PMID: 27586132]

[32]
Sakr, T.M.; Ibrahim, A.B.; Fasih, T.W.; Rashed, H.M. Preparation and biological profile of 99mTc-lidocaine as a cardioselective imaging agent using 99mTc eluted from 99Mo/99mTc generator based on Al–Mo gel. J. Radioanal. Nucl. Chem.,  2017, 314(3), 2091-2098.
 [http://dx.doi.org/10.1007/s10967-017-5560-z]

[33]
Crișan, G.; Moldovean-Cioroianu, N.S.; Timaru, D.G.; Andrieș, G.; Căinap, C.; Chiș, V. Radiopharmaceuticals for PET and SPECT imaging: A literature review over the last decade. Int. J. Mol. Sci.,  2022, 23(9), 5023.
 [http://dx.doi.org/10.3390/ijms23095023] [PMID: 35563414]

[34]
Werner, P.; Neumann, C.; Eiber, M.; Wester, H.J.; Schottelius, M. [99cmTc]Tc-PSMA-I&S-SPECT/CT: Experience in prostate cancer imaging in an outpatient center. EJNMMI Res.,  2020, 10(1), 45.
 [http://dx.doi.org/10.1186/s13550-020-00635-z] [PMID: 32382945]

[35]
Pontico, M. The prognostic value of 123 I-mIBG SPECT cardiac imaging in heart failure patients: A systematic review. J. Nucl. Cardiol.,  2022, 29(4), 1799-1809.
 [PMID: 33442819]

[36]
Klein, R. PET and SPECT tracers for myocardial perfusion imaging. Seminars in nuclear medicine; Elsevier, 2020. 
 [http://dx.doi.org/10.1053/j.semnuclmed.2020.02.016]

[37]
Shigekiyo, T.; Arawaka, S. Laterality of specific binding ratios on DAT-SPECT for differential diagnosis of degenerative parkinsonian syndromes. Sci. Rep.,  2020, 10(1), 15761.
 [http://dx.doi.org/10.1038/s41598-020-72321-y] [PMID: 32978422]

[38]
Pandey, A.; Dhiman, S.; ArunRaj, S.; Patel, C.; Bal, C.; Kumar, P. Designing and comparing performances of image processing pipeline for enhancement of I-131-metaiodobenzylguanidine images. Indian J. Nucl. Med.,  2021, 36(2), 125-133.
 [http://dx.doi.org/10.4103/ijnm.ijnm_231_20] [PMID: 34385782]

[39]
van Gils, C A J.; Beijst, C.; van Rooij, R.; de Jong, H.W A M. Impact of reconstruction parameters on quantitative I-131 SPECT. Phys. Med. Biol.,  2016, 61(14), 5166-5182.
 [http://dx.doi.org/10.1088/0031-9155/61/14/5166] [PMID: 27352225]

[40]
Autret, D.; Bitar, A.; Ferrer, L.; Lisbona, A.; Bardiès, M. Monte Carlo modeling of gamma cameras for I-131 imaging in targeted radiotherapy. Cancer Biother. Radiopharm.,  2005, 20(1), 77-84.
 [http://dx.doi.org/10.1089/cbr.2005.20.77] [PMID: 15778585]

[41]
Bahadur, S.; Pardhi, D.M.; Rautio, J.; Rosenholm, J.M.; Pathak, K. Intranasal nanoemulsions for direct nose-to-brain delivery of actives for CNS disorders. Pharmaceutics,  2020, 12(12), 1230.
 [http://dx.doi.org/10.3390/pharmaceutics12121230] [PMID: 33352959]

[42]
Sayyed, M.E.; El-Motaleb, M.A.; Ibrahim, I.T.; Rashed, H.M.; El-Nabarawi, M.A.; Ahmed, M.A. Preparation, characterization, and in vivo biodistribution study of intranasal 131I-clonazepam-loaded phospholipid magnesome as a promising brain delivery system. Eur. J. Pharm. Sci.,  2022, 169, 106089.
 [http://dx.doi.org/10.1016/j.ejps.2021.106089] [PMID: 34863872]

[43]
Rashed, H.M.; Shamma, R.N.; El-Sabagh, H.A. Preparation of 99mTc-levetiracetam intranasal microemulsion as the first radiotracer for SPECT imaging of the Synaptic Vesicle Protein SV2A. Eur. J. Pharm. Sci.,  2018, 121, 29-33.
 [http://dx.doi.org/10.1016/j.ejps.2018.05.019] [PMID: 29787786]

[44]
Brand, G. Olfactory/trigeminal interactions in nasal chemoreception. Neurosci. Biobehav. Rev.,  2006, 30(7), 908-917.
 [http://dx.doi.org/10.1016/j.neubiorev.2006.01.002] [PMID: 16545453]

[45]
Djupesland, P.G.; Messina, J.C.; Mahmoud, R.A. The nasal approach to delivering treatment for brain diseases: An anatomic, physiologic, and delivery technology overview. Ther. Deliv.,  2014, 5(6), 709-733.
 [http://dx.doi.org/10.4155/tde.14.41] [PMID: 25090283]

[46]
Hanson, L.R.; Frey, W.H., II Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci.,  2008, 9(S3)(Suppl. 3), S5.
 [http://dx.doi.org/10.1186/1471-2202-9-S3-S5] [PMID: 19091002]

[47]
Talegaonkar, S.; Mishra, P. Intranasal delivery: An approach to bypass the blood brain barrier. Indian J. Pharmacol.,  2004, 36(3), 140.

[48]
Konno, A.; Togawa, K.; Itasaka, Y. Neurophysiological mechanism of shrinkage of nasal mucosa induced by exercise. Auris Nasus Larynx,  1982, 9(2), 81-90.
 [http://dx.doi.org/10.1016/S0385-8146(82)80004-7] [PMID: 7159302]

[49]
Susaman, N.; Cingi, C.; Mullol, J. Is the nasal cycle real? How important is it?; Challenges in Rhinology, 2021, pp. 1-8.
 [http://dx.doi.org/10.1007/978-3-030-50899-9_1]

[50]
Torchilin, V.P. Structure and design of polymeric surfactant-based drug delivery systems. J. Control. Release,  2001, 73(2-3), 137-172.
 [http://dx.doi.org/10.1016/S0168-3659(01)00299-1] [PMID: 11516494]

[51]
Adams, M.L.; Andes, D.R.; Kwon, G.S. Amphotericin B encapsulated in micelles based on poly(ethylene oxide)-block-poly(L-amino acid) derivatives exerts reduced in vitro hemolysis but maintains potent in vivo antifungal activity. Biomacromolecules,  2003, 4(3), 750-757.
 [http://dx.doi.org/10.1021/bm0257614] [PMID: 12741794]

[52]
Yokoyama, M. Polymeric micelles for the targeting of hydrophobic drugs. Polymeric Drug Deliv. Syst.,  2005, 148, 533-576.
 [http://dx.doi.org/10.1201/9780849348129.ch13]

[53]
Kanazawa, T. Brain delivery of small interfering ribonucleic acid and drugs through intranasal administration with nano-sized polymer micelles.,  Medical Devices: Evidence and Research,  2015, 57-64.
 [http://dx.doi.org/10.2147/MDER.S70856]

[54]
Nour, S.A.; Abdelmalak, N.S.; Naguib, M.J.; Rashed, H.M.; Ibrahim, A.B. Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies. Drug Deliv.,  2016, 23(9), 3681-3695.
 [http://dx.doi.org/10.1080/10717544.2016.1223216] [PMID: 27648847]

[55]
Lv, S.; Wu, Y.; Cai, K.; He, H.; Li, Y.; Lan, M.; Chen, X.; Cheng, J.; Yin, L. High drug loading and sub-quantitative loading efficiency of polymeric micelles driven by donor–receptor coordination interactions. J. Am. Chem. Soc.,  2018, 140(4), 1235-1238.
 [http://dx.doi.org/10.1021/jacs.7b12776] [PMID: 29332390]

[56]
Oerlemans, C.; Bult, W.; Bos, M.; Storm, G.; Nijsen, J.F.W.; Hennink, W.E. Polymeric micelles in anticancer therapy: Targeting, imaging and triggered release. Pharm. Res.,  2010, 27(12), 2569-2589.
 [http://dx.doi.org/10.1007/s11095-010-0233-4] [PMID: 20725771]

[57]
Lamptey, R.N.L.; Gothwal, A.; Trivedi, R.; Arora, S.; Singh, J. Synthesis and characterization of fatty acid grafted chitosan polymeric micelles for improved gene delivery of VGF to the brain through intranasal route. Biomedicines,  2022, 10(2), 493.
 [http://dx.doi.org/10.3390/biomedicines10020493] [PMID: 35203704]

[58]
Rashed, H.M.; Ibrahim, I.T.; Motaleb, M.A. 99mTc-hexoprenaline and 131I-dapoxetine: Preparation, in silico modeling and biological evaluation as promising lung scintigraphy radiopharmaceuticals. J. Radioanal. Nucl. Chem.,  2017, 314(2), 1297-1307.
 [http://dx.doi.org/10.1007/s10967-017-5500-y]

[59]
Robles, A.M.; Balter, H.S.; Oliver, P.; Welling, M.M.; Pauwels, E.K.J. Improved radioiodination of biomolecules using exhaustive Chloramine-T oxidation. Nucl. Med. Biol.,  2001, 28(8), 999-1008.
 [http://dx.doi.org/10.1016/S0969-8051(01)00261-X] [PMID: 11711320]

[60]
Rashed, H.M.; Ibrahim, I.T.; Motaleb, M.A.; El-Bary, A.A. Preparation of radioiodinated ritodrine as a potential agent for lung imaging. J. Radioanal. Nucl. Chem.,  2014, 300(3), 1227-1233.
 [http://dx.doi.org/10.1007/s10967-014-3077-2]

[61]
Saha, G.B.; Saha, G.B. Radiopharmaceuticals and general methods of radiolabeling. fundamentals of nuclear pharmacy,  2018, 93-121.

[62]
Ramdhani, D.; Widyasari, E.M.; Sriyani, M.E.; Arnanda, Q.P.; Watabe, H. Iodine-131 labeled genistein as a potential radiotracer for breast cancer. Heliyon,  2020, 6(9), e04780.
 [http://dx.doi.org/10.1016/j.heliyon.2020.e04780] [PMID: 33005774]

[63]
Ibrahim, A.B.; Sakr, T.M.; Khoweysa, O.M.A.; Motaleb, M.A.; Abd El-Bary, A.; El-Kolaly, M.T. Radioiodinated anastrozole and epirubicin as potential targeting radiopharmaceuticals for solid tumor imaging. J. Radioanal. Nucl. Chem.,  2015, 303(1), 967-975.
 [http://dx.doi.org/10.1007/s10967-014-3560-9]

[64]
Shewaiter, M.A.; Selim, A.A.; Moustafa, Y.M.; Gad, S.; Rashed, H.M. Radioiodinated acemetacin loaded niosomes as a dual anticancer therapy. Int. J. Pharm.,  2022, 628, 122345.
 [http://dx.doi.org/10.1016/j.ijpharm.2022.122345] [PMID: 36349611]

[65]
Darwish, W.M.; Bayoumi, N.A.; El-Shershaby, H.M.; Allahloubi, N.M. Targeted photoimmunotherapy based on photosensitizerantibody conjugates for multiple myeloma treatment. J. Photochem. Photobiol. B,  2020, 203, 111777.
 [http://dx.doi.org/10.1016/j.jphotobiol.2020.111777] [PMID: 31931387]

[66]
Plotzke, K.P.; Fisher, S.J.; Wahl, R.L.; Olken, N.M.; Skinner, S.; Gross, M.D.; Counsell, R.E. Selective localization of a radioiodinated phospholipid ether analog in human tumor xenografts. J. Nucl. Med.,  1993, 34(5), 787-792.
 [PMID: 8386759]

[67]
Ahmed, I.S.; Rashed, H.M.; Fayez, H.; Farouk, F.; Shamma, R.N. Nanoparticle-mediated dual targeting: An approach for enhanced baicalin delivery to the liver. Pharmaceutics,  2020, 12(2), 107.
 [http://dx.doi.org/10.3390/pharmaceutics12020107] [PMID: 32013203]

[68]
Ghoreishi, S.M.; Khalaj, A.; Sabzevari, O.; Badrzadeh, L.; Mohammadzadeh, P.; Mousavi Motlagh, S.S.; Bitarafan-Rajabi, A.; Shafiee Ardestani, M. Technetium-99m chelator-free radiolabeling of specific glutamine tumor imaging nanoprobe: In vitro and in vivo evaluations. Int. J. Nanomedicine,  2018, 13, 4671-4683.
 [http://dx.doi.org/10.2147/IJN.S157426] [PMID: 30154653]

[69]
Salama, A.H.; Shamma, R.N. Tri/tetra-block co-polymeric nanocarriers as a potential ocular delivery system of lornoxicam: In-vitro characterization, and in-vivo estimation of corneal permeation. Int. J. Pharm.,  2015, 492(1-2), 28-39.
 [http://dx.doi.org/10.1016/j.ijpharm.2015.07.010] [PMID: 26151106]

[70]
Sayed, S.; Elsharkawy, F.M.; Amin, M.M.; Shamsel-Din, H.A.; Ibrahim, A.B. Brain targeting efficiency of intranasal clozapine-loaded mixed micelles following radio labeling with Technetium-99m. Drug Deliv.,  2021, 28(1), 1524-1538.
 [http://dx.doi.org/10.1080/10717544.2021.1951895] [PMID: 34266360]

[71]
Abdelbary, G.A.; Tadros, M.I. Brain targeting of olanzapine via intranasal delivery of core–shell difunctional block copolymer mixed nanomicellar carriers: In vitro characterization, ex vivo estimation of nasal toxicity and in vivo biodistribution studies. Int. J. Pharm.,  2013, 452(1-2), 300-310.
 [http://dx.doi.org/10.1016/j.ijpharm.2013.04.084] [PMID: 23684658]

[72]
Helmy, H.; El-Sahar, A.; Sayed, R.; Shamma, R.; Salama, A.; El-Baz, E. Therapeutic effects of lornoxicam-loaded nanomicellar formula in experimental models of rheumatoid arthritis. Int. J. Nanomedicine,  2017, 12, 7015-7023.
 [http://dx.doi.org/10.2147/IJN.S147738] [PMID: 29026298]

[73]
Sakai, T.; Kurosawa, H.; Okada, T.; Mishima, S. Vesicle formation in mixture of a PEO-PPO-PEO block copolymer (Pluronic P123) and a nonionic surfactant (Span 65) in water. Colloids Surf. A Physicochem. Eng. Asp.,  2011, 389(1-3), 82-89.
 [http://dx.doi.org/10.1016/j.colsurfa.2011.08.046]

[74]
Mehra, N.; Aqil, M.; Sultana, Y. A grafted copolymer-based nanomicelles for topical ocular delivery of everolimus: Formulation, characterization, ex-vivo permeation, in-vitro ocular toxicity, and stability study. Eur. J. Pharm. Sci.,  2021, 159, 105735.
 [http://dx.doi.org/10.1016/j.ejps.2021.105735] [PMID: 33516808]

[75]
Lin, A.C.; Goh, M.C. Investigating the ultrastructure of fibrous long spacing collagen by parallel atomic force and transmission electron microscopy. Proteins,  2002, 49(3), 378-384.
 [http://dx.doi.org/10.1002/prot.10224] [PMID: 12360527]

[76]
Francis, M.F.; Lavoie, L.; Winnik, F.M.; Leroux, J.C. Solubilization of cyclosporin A in dextran-g-polyethyleneglycolalkyl ether polymeric micelles. Eur. J. Pharm. Biopharm.,  2003, 56(3), 337-346.
 [http://dx.doi.org/10.1016/S0939-6411(03)00111-5] [PMID: 14602175]

[77]
Sosnik, A.; Imperiale, J.C.; Vázquez-González, B.; Raskin, M.M.; Muñoz-Muñoz, F.; Burillo, G.; Cedillo, G.; Bucio, E. Mucoadhesive thermo-responsive chitosan- g -poly(N -isopropylacrylamide) polymeric micelles via a one-pot gamma-radiation-assisted pathway. Colloids Surf. B Biointerfaces,  2015, 136, 900-907.
 [http://dx.doi.org/10.1016/j.colsurfb.2015.10.036] [PMID: 26551867]

[78]
Basalious, E.B.; Shamma, R.N. Novel self-assembled nano-tubular mixed micelles of Pluronics P123, Pluronic F127 and phosphatidylcholine for oral delivery of nimodipine: In vitro characterization, ex vivo transport and in vivo pharmacokinetic studies. Int. J. Pharm.,  2015, 493(1-2), 347-356.
 [http://dx.doi.org/10.1016/j.ijpharm.2015.07.075] [PMID: 26241752]

[79]
Meredith, M.E.; Salameh, T.S.; Banks, W.A. Intranasal delivery of proteins and peptides in the treatment of neurodegenerative diseases. AAPS J.,  2015, 17(4), 780-787.
 [http://dx.doi.org/10.1208/s12248-015-9719-7] [PMID: 25801717]

[80]
Waterhouse, R. Determination of lipophilicity and its use as a predictor of blood–brain barrier penetration of molecular imaging agents. Mol. Imaging Biol.,  2003, 5(6), 376-389.
 [http://dx.doi.org/10.1016/j.mibio.2003.09.014] [PMID: 14667492]

[81]
Banks, W.A. Characteristics of compounds that cross the bloodbrain barrier. BMC Neurol.,  2009, 9(Suppl 1), S3.
 [http://dx.doi.org/10.1186/1471-2377-9-S1-S3] [PMID: 19534732]

[82]
Mooney, M.P. The Johns Hopkins Atlas of Human Functional Anatomy , 1999. 

[83]
Vyas, T.K.; Babbar, A.K.; Sharma, R.K.; Misra, A. Intranasal mucoadhesive microemulsions of zolmitriptan: Preliminary studies on brain-targeting. J. Drug Target.,  2005, 13(5), 317-324.
 [http://dx.doi.org/10.1080/10611860500246217] [PMID: 16199375]

[84]
Kulkarni, A.D.; Patel, H.M.; Surana, S.J.; Belgamwar, V.S.; Pardeshi, C.V. Brain–blood ratio: Implications in brain drug delivery. Expert Opin. Drug Deliv.,  2016, 13(1), 85-92.
 [http://dx.doi.org/10.1517/17425247.2016.1092519] [PMID: 26393289]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0118744710269885231113070356	Print ISSN 1874-4710
Publisher Name Bentham Science Publisher	Online ISSN 1874-4729
Current Radiopharmaceuticals

Intranasal Radioiodinated Ferulic Acid Polymeric Micelles as the First Nuclear Medicine Imaging Probe for ETRA Brain Receptor

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
