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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Trojan Microparticles Potential for Ophthalmic Drug Delivery

Author(s): Sergio Esteban-Pérez, Irene Bravo-Osuna*, Vanessa Andrés-Guerrero, Irene T. Molina-Martínez and Rocío Herrero-Vanrell

Volume 27, Issue 4, 2020

Page: [570 - 582] Pages: 13

DOI: 10.2174/0929867326666190905150331

Price: $65

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The administration of drugs to treat ocular disorders still remains a technological challenge in this XXI century. Although there is an important arsenal of active molecules useful to treat ocular diseases, ranging from classical compounds to biotechnological products, currenty, no ideal delivery system is able to profit all their therapeutic potential. Among the Intraocular Drug Delivery Systems (IODDS) proposed to overcome some of the most important limitations, microsystems and nanosystems have raised high attention. While microsystems are able to offer long-term release after intravitreal injection, nanosystems can protect the active compound from external environment (reducing their clearance) and direct it to its target tissues. In recent years, some researchers have explored the possibility of combining micro and nanosystems in “Nanoparticle-in-Microparticle (NiMs)” systems or “trojan systems”. This excellent idea is not exempt of technological problems, remains partially unsolved, especially in the case of IODDS. The objective of the present review is to show the state of art concerning the design, preparation and characterization of trojan microparticles for drug delivery and to remark their potential and limitations as IODDS, one of the most important challenges faced by pharmaceutical technology at the moment.

Keywords: Trojan systems, Nanoparticles-in-Microparticles (MiMs), ophthalmic drug delivery, posterior segment, intravitreal injection, Intraocular Drug Delivery Systems (IODDS).

Kim, Y.C.; Chiang, B.; Wu, X.; Prausnitz, M.R. Ocular delivery of macromolecules. J. Control. Release, 2014, 190, 172-181.
[] [PMID: 24998941]
Herrero-Vanrell, R.; Vicario de la Torre, M.; Andrés-Guerrero, V.; Barbosa-Alfaro, D.; Molina-Martínez, I.T.; Bravo-Osuna, I. Nano and microtechnologies for ophthalmic administration: an overview. J. Drug Deliv. Sci. Technol., 2013, 23(2), 75-102.
Zhou, A.X.; Messenger, W.B.; Sargent, S.; Ambati, B.K. Safety of undiluted intracameral moxifloxacin without postoperative topical antibiotics in cataract surgery. Int. Ophthalmol., 2016, 36(4), 493-498.
[] [PMID: 26577588]
Yao, J.; Tucker, B.A.; Zhang, X.; Checa-Casalengua, P.; Herrero-Vanrell, R.; Young, M.J. Robust cell integration from co-transplantation of biodegradable MMP2-PLGA microspheres with retinal progenitor cells. Biomaterials, 2011, 32(4), 1041-1050.
[] [PMID: 21030072]
Del Amo, E.M.; Rimpelä, A.K.; Heikkinen, E.; Kari, O.K.; Ramsay, E.; Lajunen, T.; Schmitt, M.; Pelkonen, L.; Bhattacharya, M.; Richardson, D.; Subrizi, A.; Turunen, T.; Reinisalo, M.; Itkonen, J.; Toropainen, E.; Casteleijn, M.; Kidron, H.; Antopolsky, M.; Vellonen, K.S.; Ruponen, M.; Urtti, A. Pharmacokinetic aspects of retinal drug delivery. Prog. Retin. Eye Res., 2017, 57, 134-185.
[] [PMID: 28028001]
Herrero-Vanrell, R.; Bravo-Osuna, I.; Andrés-Guerrero, V.; Vicario-de-la-Torre, M.; Molina-Martínez, I.T. The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies. Prog. Retin. Eye Res., 2014, 42, 27-43.
[] [PMID: 24819336]
Bravo-Osuna, I.; Andrés-Guerrero, V.; Pastoriza Abal, P.; Molina-Martínez, I.T.; Herrero-Vanrell, R. Pharmaceutical microscale and nanoscale approaches for efficient treatment of ocular diseases. Drug Deliv. Transl. Res., 2016, 6(6), 686-707.
[] [PMID: 27766598]
Bravo-Osuna, I.; Andrés-Guerrero, V.; Arranz-Romera, A.; Esteban-Pérez, S.; Molina-Martínez, I.T.; Herrero-Vanrell, R. Microspheres as intraocular therapeutic tools in chronic diseases of the optic nerve and retina. Adv. Drug Deliv. Rev., 2018, 126, 127-144.
[] [PMID: 29339146]
Cardillo, J.A.; Souza-Filho, A.A.; Oliveira, A.G. Intravitreal bioerudivel sustained-release triamcinolone microspheres system (RETAAC). Preliminary report of its potential usefulness for the treatment of diabetic macular edema. Arch. Soc. Esp. Oftalmol., 2006, 81(12), 675-677, 679-681.
[PMID: 17199160]
Checa-Casalengua, P.; Jiang, C.; Bravo-Osuna, I.; Tucker, B.A.; Molina-Martínez, I.T.; Young, M.J.; Herrero-Vanrell, R. Retinal ganglion cells survival in a glaucoma model by GDNF/Vit E PLGA microspheres prepared according to a novel microencapsulation procedure. J. Control. Release, 2011, 156(1), 92-100.
[] [PMID: 21704662]
García-Caballero, C.; Prieto-Calvo, E.; Checa-Casalengua, P.; García-Martín, E.; Polo-Llorens, V.; García-Feijoo, J.; Molina-Martínez, I.T.; Bravo-Osuna, I.; Herrero-Vanrell, R. Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits. Eur. J. Pharm. Sci., 2017, 103, 19-26.
[] [PMID: 28259830]
Yoshida, T.; Gong, J.; Xu, Z.; Wei, Y.; Duh, E.J. Inhibition of pathological retinal angiogenesis by the integrin αvβ3 antagonist tetraiodothyroacetic acid (tetrac). Exp. Eye Res., 2012, 94(1), 41-48.
[] [PMID: 22123068]
Park, K.; Chen, Y.; Hu, Y.; Mayo, A.S.; Kompella, U.B.; Longeras, R.; Ma, J.X. Nanoparticle-mediated expression of an angiogenic inhibitor ameliorates ischemia-induced retinal neovascularization and diabetes-induced retinal vascular leakage. Diabetes, 2009, 58(8), 1902-1913.
[] [PMID: 19491211]
Crooke, S.T. Vitravene-another piece in the mosaic. Antisense Nucleic Acid Drug Dev., 1998, 8(4), vii-viii.
[] [PMID: 9743463]
Rayburn, E.R.; Zhang, R. Antisense, RNAi, and gene silencing strategies for therapy: mission possible or impossible? Drug Discov. Today, 2008, 13(11-12), 513-521.
[] [PMID: 18549978]
Marano, R.J.; Toth, I.; Wimmer, N.; Brankov, M.; Rakoczy, P.E. Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: a long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity. Gene Ther., 2005, 12(21), 1544-1550.
[] [PMID: 16034458]
Bhavsar, M.D.; Amiji, M.M. Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS). J. Control. Release, 2007, 119(3), 339-348.
[] [PMID: 17475358]
Bhavsar, M.D.; Amiji, M.M. Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease. Gene Ther., 2008, 15(17), 1200-1209.
[] [PMID: 18418416]
Bhavsar, M.D.; Tiwari, S.B.; Amiji, M.M. Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design. J. Control. Release, 2006, 110(2), 422-430.
[] [PMID: 16338017]
Kriegel, C.; Amiji, M.M. Dual TNF-α/Cyclin D1 gene silencing with an oral polymeric microparticle system as a novel strategy for the treatment of inflammatory bowel disease. Clin. Transl. Gastroenterol, 2011, 2(3), 2e2.
[] [PMID: 23237848]
Lee, Y.S.; Johnson, P.J.; Robbins, P.T.; Bridson, R.H. Production of nanoparticles-in-microparticles by a double emulsion method: a comprehensive study. Eur. J. Pharm. Biopharm., 2013, 83(2), 168-173.
[] [PMID: 23153669]
Chen, Z.; Liu, D.; Wang, J.; Wu, L.; Li, W.; Chen, J.; Cai, B.C.; Cheng, H. Development of nanoparticles-in-microparticles system for improved local retention after intra-articular injection. Drug Deliv., 2014, 21(5), 342-350.
[] [PMID: 24215110]
Farris, E.; Brown, D.M.; Ramer-Tait, A.E.; Pannier, A.K. Chitosan-zein nano-in-microparticles capable of mediating in vivo transgene expression following oral delivery. J. Control. Release, 2017, 249, 150-161.
[] [PMID: 28153762]
Khan, I.U.; Serra, C.A.; Anton, N.; Er-Rafik, M.; Blanck, C.; Schmutz, M.; Kraus, I.; Messaddeq, N.; Sutter, C.; Anton, H.; Klymchenko, A.S.; Vandamme, T.F. Microfluidic conceived trojan microcarriers for oral delivery of nanoparticles. Int. J. Pharm., 2015, 493(1-2), 7-15.
[] [PMID: 26116014]
Guo, X.; Xia, T.; Wang, H.; Chen, F.; Cheng, R.; Luo, X.; Li, X. Electrosprayed microparticles with loaded pDNA-calcium phosphate nanoparticles to promote the regeneration of mature blood vessels. Pharm. Res., 2014, 31(4), 874-886.
[] [PMID: 24065597]
Elbaz, N.M.; Khalil, I.A.; Abd-Rabou, A.A.; El-Sherbiny, I.M. Chitosan-based nano-in-microparticle carriers for enhanced oral delivery and anticancer activity of propolis. Int. J. Biol. Macromol., 2016, 92, 254-269.
[] [PMID: 27397719]
Ozeki, T.; Akiyama, Y.; Takahashi, N.; Tagami, T.; Tanaka, T.; Fujii, M.; Okada, H. Development of a novel and customizable two-solution mixing type spray nozzle for one-step preparation of nanoparticle-containing microparticles. Biol. Pharm. Bull., 2012, 35(11), 1926-1931.
[] [PMID: 23123464]
Deng, Y.; Mathaes, R.; Winter, G.; Engert, J. Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection. Eur. J. Pharm. Sci., 2014, 63, 154-166.
[] [PMID: 25042055]
Tewes, F.; Ehrhardt, C.; Healy, A.M. Superparamagnetic iron oxide nanoparticles (SPIONs)-loaded Trojan microparticles for targeted aerosol delivery to the lung. Eur. J. Pharm. Biopharm., 2014, 86(1), 98-104.
[] [PMID: 24055690]
Bakhtiary, Z.; Barar, J.; Aghanejad, A.; Saei, A.A.; Nemati, E.; Ezzati Nazhad Dolatabadi, J.; Omidi, Y. Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer. Drug Dev. Ind. Pharm., 2017, 43(8), 1244-1253.
[] [PMID: 28323493]
Schulze, J.; Kuhn, S.; Hendrikx, S.; Schulz-Siegmund, M.; Polte, T.; Aigner, A. Spray-dried nanoparticle-in-microparticle delivery systems (NiMDS) for gene delivery, comprising polyethylenimine (PEI)-based nanoparticles in a poly(vinyl alcohol) matrix. Small, 2018, 14(12)e1701810
Pinkerton, N.M.; Zhang, S.W.; Youngblood, R.L.; Gao, D.; Li, S.; Benson, B.R.; Anthony, J.; Stone, H.A.; Sinko, P.J.; Prud’homme, R.K. Gelation chemistries for the encapsulation of nanoparticles in composite gel microparticles for lung imaging and drug delivery. Biomacromolecules, 2014, 15(1), 252-261.
[] [PMID: 24410445]
Garrait, G.; Beyssac, E.; Subirade, M. Development of a novel drug delivery system: chitosan nanoparticles entrapped in alginate microparticles. J. Microencapsul., 2014, 31(4), 363-372.
[] [PMID: 24697173]
Gómez-Gaete, C.; Fattal, E.; Silva, L.; Besnard, M.; Tsapis, N. Dexamethasone acetate encapsulation into Trojan particles. J. Control. Release, 2008, 128(1), 41-49.
[] [PMID: 18374442]
Algvere, P.; Bill, A. Drainage of microspheres and RBCs from the vitreous of aphakic and phakic eyes. Archives of ophthalmology,, 1979, 97(7), 1333-1336.
[] [PMID: 454274]
Martens, T.F.; Vercauteren, D.; Forier, K.; Deschout, H.; Remaut, K.; Paesen, R.; Ameloot, M.; Engbersen, J.F.; Demeester, J.; De Smedt, S.C.; Braeckmans, K. Measuring the intravitreal mobility of nanomedicines with single-particle tracking microscopy. Nanomedicine (Lond.), 2013, 8(12), 1955-1968.
[] [PMID: 23438206]
Koo, H.; Moon, H.; Han, H.; Na, J.H.; Huh, M.S.; Park, J.H.; Woo, S.J.; Park, K.H.; Kwon, I.C.; Kim, K.; Kim, H. The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection. Biomaterials, 2012, 33(12), 3485-3493.
[] [PMID: 22322197]
Prow, T.W. Toxicity of nanomaterials to the eye. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2010, 2(4), 317-333.
[] [PMID: 20077524]
Amrite, A.C.; Kompella, U.B. Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration. J. Pharm. Pharmacol., 2005, 57(12), 1555-1563.
[] [PMID: 16354399]
Sherif, Z.; Pleyer, U. Corticosteroids in ophthalmology: past-present-future. Ophthalmologica, 2002, 216(5), 305-315.
[] [PMID: 12424394]
Yandrapu, S.K.; Upadhyay, A.K.; Petrash, J.M.; Kompella, U.B. Nanoparticles in porous microparticles prepared by supercritical infusion and pressure quench technology for sustained delivery of bevacizumab. Mol. Pharm., 2013, 10(12), 4676-4686.
[] [PMID: 24131101]
Elsaid, N.; Jackson, T.L.; Elsaid, Z.; Alqathama, A.; Somavarapu, S. PLGA Microparticles entrapping chitosan-based nanoparticles for the ocular delivery of ranibizumab. Mol. Pharm., 2016, 13(9), 2923-2940.
[] [PMID: 27286558]
Messina, M.; Dua, H.S. Early results on the use of chitosan-N-acetylcysteine (Lacrimera(R)) in the management of dry eye disease of varied etiology. Int. Ophthalmol., 2019, 39(3), 693-696.
[] [PMID: 29549486]

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