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Effect of Ultra-Small Chitosan Nanoparticles Doped with Brimonidine on the Ultra-Structure of the Trabecular Meshwork of Glaucoma Patients

Published online by Cambridge University Press:  25 April 2019

Indu Barwal ,
Rahul Kumar ,
Tanuj Dada  and
Subhash Chandra Yadav
Indu Barwal
Affiliation:
Department of Anatomy, Nanotechnology Lab, Electron Microscope Facility, All India Institute of Medical Sciences, New Delhi 110029, India
Rahul Kumar
Affiliation:
Department of Anatomy, Nanotechnology Lab, Electron Microscope Facility, All India Institute of Medical Sciences, New Delhi 110029, India
Tanuj Dada
Affiliation:
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India
Subhash Chandra Yadav*
Affiliation:
Department of Anatomy, Nanotechnology Lab, Electron Microscope Facility, All India Institute of Medical Sciences, New Delhi 110029, India
*
*Author for correspondence: Subhash Chandra Yadav, E-mail: [email protected]
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Abstract

Brimonidine, an anti-glaucoma medicine, acts as an adrenergic agonist which decreases the synthesis of aqueous humour and increases the amount of drainage through Schlemm's canal and trabecular meshwork, but shows dose-dependent (0.2% solution thrice daily) toxicity. To reduce the side effects and improve the efficacy, brimonidine was nanoencapsulated on ultra-small-sized chitosan nanoparticles (nanobrimonidine) (28 ± 4 nm) with 39% encapsulation efficiency, monodispersity, freeze–thawing capability, storage stability, and 2% drug loading capacity. This nanocomplex showed burst, half, and complete release at 0.5, 45, and 100 h, respectively. Nanobrimonidine did not show any in vitro toxicity and was taken up by caveolae-mediated endocytosis. The nanobrimonidine-treated trabeculectomy tissue of glaucoma patients showed better dilation of the trabecular meshwork under the electron microscope. This is direct evidence for better bioavailability of nanobrimonidine after topical administration. Thus, the developed nanobrimonidine has the potential to improve the efficacy, reduce dosage and frequency, and improve delivery to the anterior chamber of the eye.

Keywords

brimonidineglaucomananobrimonidinenanoencapsulationultra-small chitosan nanoparticles
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 25 , Issue 6 , December 2019 , pp. 1352 - 1366
Copyright
Copyright © Microscopy Society of America 2019 

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References

Aburahma, MH & Mahmoud, AA (2011). Biodegradable ocular inserts for sustained delivery of brimonidine tartarate: Preparation and in vitro/in vivo evaluation. AAPS PharmSciTech 12(4), 1335–1347.Google Scholar
Acheampong, AA, Small, D, Baumgarten, V, Welty, D & Tang-Liu, D (2002). Formulation effects on ocular absorption of brimonidine in rabbit eyes. J Ocul Pharmacol Ther 18(4), 325–337.Google Scholar
Agnihotri, SA, Mallikarjuna, NN & Aminabhavi, TM (2004). Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release 100(1), 5–28.Google Scholar
Aksungur, P, Demirbilek, M, Denkbas, EB, Vandervoort, J, Ludwig, A & Unlu, N (2011). Development and characterization of cyclosporine A loaded nanoparticles for ocular drug delivery: Cellular toxicity, uptake, and kinetic studies. J Control Release 151(3), 286–294.Google Scholar
Almeida, H, Amaral, MH, Lobao, P & Sousa Lobo, JM (2013). Applications of poloxamers in ophthalmic pharmaceutical formulations: An overview. Expert Opin Drug Deliv 10(9), 1223–1237.Google Scholar
Almeida, H, Amaral, MH, Lobao, P & Lobo, JM (2014). In situ gelling systems: A strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug Discov Today 19(4), 400–412.Google Scholar
Alonso, MJ & Sanchez, A (2003). The potential of chitosan in ocular drug delivery. J Pharm Pharmacol 55(11), 1451–1463.Google Scholar
Anderberg, EK, Bisrat, M & Nyström, C (1988). Physiochemical aspects of drug release. VII. The effect of surfactant concentration and drug particle size on solubility and dissolution rate of felodipine, a sparingly soluble drug. Int J Pharm 47(1–3), 67–77.Google Scholar
Banerjee, T, Mitra, S, Kumar Singh, A, Kumar Sharma, R & Maitra, A (2002). Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. Int J Pharm 243(1–2), 93–105.Google Scholar
Binks, BP & Lumsdon, SO (2001). Pickering emulsions stabilized by monodispersed latex particles: Effects of particle size. Langmuir 17(15), 4540–4547.Google Scholar
Bonferoni, MC, Sandri, G, Rossi, S, Ferrari, F & Caramella, C (2009). Chitosan and its salts for mucosal and transmucosal delivery. Expert Opin Drug Deliv 6(9), 923–939.Google Scholar
Bowman, RJ, Cope, J & Nischal, KK (2004). Ocular and systemic side effects of brimonidine 0.2% eye drops (Alphagan) in children. Eye (Lond) 18(1), 24–26.Google Scholar
Calvo, P, Remu án-López, C, Vila-Jato, JL & Alonso, MJ (1997). Novel hydrophilic chitosan–polyethylene oxide nanoparticles as protein carriers. J Appl Polym Sci 63, 125–132.Google Scholar
Cantor, LB (2006). Brimonidine in the treatment of glaucoma and ocular hypertension. Ther Clin Risk Manag 2(4), 337–346.Google Scholar
Chen, F, Zhang, ZR & Huang, Y (2007). Evaluation and modification of N-trimethyl chitosan chloride nanoparticles as protein carriers. Int J Pharm 336(1), 166–173.Google Scholar
Cho, IS, Park, CG, Huh, BK, Cho, MO, Khatun, Z, Li, Z, Kang, SW, Choy, YB & Huh, KM (2016). Thermosensitive hexanoyl glycol chitosan-based ocular delivery system for glaucoma therapy. Acta Biomater 39, 124–132.Google Scholar
De, TK, Rodman, DJ, Holm, BA, Prasad, PN & Bergey, EJ (2003). Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery. J Microencapsul 20(3), 361–374.Google Scholar
De Campos, AM, Sanchez, A & Alonso, MJ (2001). Chitosan nanoparticles: A new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm 224(1–2), 159–168.Google Scholar
de Campos, AM, Diebold, Y, Carvalho, EL, Sanchez, A & Alonso, MJ (2004). Chitosan nanoparticles as new ocular drug delivery systems: In vitro stability, in vivo fate, and cellular toxicity. Pharm Res 21(5), 803–810.Google Scholar
de la Fuente, M, Seijo, B & Alonso, MJ (2008). Novel hyaluronic acid-chitosan nanoparticles for ocular gene therapy. Invest Ophthalmol Vis Sci 49(5), 2016–2024.Google Scholar
Elzatahry, AA & Eldin, MSM (2008). Preparation and characterization of metronidazole-loaded chitosan nanoparticles for drug delivery application. Polym Adv Technol 19(12), 1787–1791.Google Scholar
Fan, W, Yan, W, Xu, Z & Ni, H (2012). Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surf B Biointerfaces 90, 21–27.Google Scholar
Hagens, WI, Oomen, AG, de Jong, WH, Cassee, FR & Sips, AJ (2007). What do we (need to) know about the kinetic properties of nanoparticles in the body? Regul Toxicol Pharmacol 49(3), 217–229.Google Scholar
Ibrahim, MM, Abd-Elgawad, AH, Soliman, OA & Jablonski, MM (2015). Natural bioadhesive biodegradable nanoparticle-based topical ophthalmic formulations for management of glaucoma. Transl Vis Sci Technol 4(3), 12.Google Scholar
Jarvinen, K, Jarvinen, T & Urtti, A (1995). Ocular absorption following topical delivery. Adv Drug Deliv Rev 16, 3–19.Google Scholar
Kim, SN, Ko, SA, Park, CG, Lee, SH, Huh, BK, Park, YH, Kim, YK, Ha, A, Park, KH & Choy, YB (2018). Amino-functionalized mesoporous silica particles for ocular delivery of brimonidine. Mol Pharm 15(8), 3143–3152.Google Scholar
Lehr, CM, Bowstra, JA, Schacht, EH & Juginger, HE (1992). In vitro evaluation of mucoadhesive properties of chitosan and some others natural polymers. Int J Pharm 78, 43–48.Google Scholar
Luo, Q, Zhao, J, Zhang, X & Pan, W (2011). Nanostructured lipid carrier (NLC) coated with chitosan oligosaccharides and its potential use in ocular drug delivery system. Int J Pharm 403(1–2), 185–191.Google Scholar
Maiti, S, Paul, S, Mondol, R, Ray, S & Sa, B (2011). Nanovesicular formulation of brimonidine tartrate for the management of glaucoma: In vitro and in vivo evaluation. AAPS PharmSciTech 12(2), 755–763.Google Scholar
Malhotra, M, Kulamarva, A, Sebak, S, Paul, A, Bhathena, J, Mirzaei, M & Prakash, S (2009). Ultrafine chitosan nanoparticles as an efficient nucleic acid delivery system targeting neuronal cells. Drug Dev Ind Pharm 35(6), 719–726.Google Scholar
Motwani, SK, Chopra, S, Talegaonkar, S, Kohli, K, Ahmad, FJ & Khar, RK (2008). Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: Formulation, optimisation and in vitro characterisation. Eur J Pharm Biopharm 68(3), 513–525.Google Scholar
Mundada, AS & Avari, JG (2009). In situ gelling polymers in ocular drug delivery systems: A review. Crit Rev Ther Drug Carrier Syst 26(1), 85–118.Google Scholar
Natarajan, JV, Darwitan, A, Barathi, VA, Ang, M, Htoon, HM, Boey, F, Tam, KC, Wong, TT & Venkatraman, SS (2014). Sustained drug release in nanomedicine: A long-acting nanocarrier-based formulation for glaucoma. ACS Nano 8(1), 419–429.Google Scholar
Newton, MJ & Rimple, (2018) Impact of ocular compatible Lipoids and Castor oil in fabrication of brimonidine tartrate nanoemulsions by 33 full factorial design. Recent Pat Inflamm Allergy Drug Discov.Google Scholar
Paolicelli, P, de la Fuente, M, Sanchez, A, Seijo, B & Alonso, MJ (2009). Chitosan nanoparticles for drug delivery to the eye. Expert Opin Drug Deliv 6(3), 239–253.Google Scholar
Prabhu, P, Nitish, KR, Koland, M, Harish, N, Vijayanarayan, K, Dhondge, G & Charyulu, R (2010). Preparation and evaluation of nano-vesicles of brimonidine tartrate as an ocular drug delivery system. J Young Pharm 2(4), 356–361.Google Scholar
Qun, G & Ajun, W (2006). Effects of molecular weight, degree of acetylation and ionic strength on surface tension of chitosan in dilute solution. Carbohydr Polym 64, 29–36.Google Scholar
Santra, S (2010). Chitosan-based nanoparticles and methods for making and using the same. In 20110158901, US, O. F. (Ed.), USA.Google Scholar
Santra, S & Tallury, P (2011). Ultra-small chitosan nanoparticles useful as bioimaging agents and methods of making same. FSU (Ed.), USA: US20110021745A1.Google Scholar
Shahrouz, T, Seyedali, M, Mehdi, M & Hossein, D (2014). Development of ultrasmall chitosan/succinyl β-cyclodextrin nanoparticles as a sustained protein-delivery system. J Appl Polym Sci 131(1), 39648–39648.Google Scholar
Shang, L, Nienhaus, K & Nienhaus, GU (2014). Engineered nanoparticles interacting with cells: Size matters. J Nanobiotechnology 12, 5.Google Scholar
Shi, S, Fliss, BC, Gu, Z, Zhu, Y, Hong, H, Valdovinos, HF, Hernandez, R, Goel, S, Luo, H, Chen, F, Barnhart, TE, Nickles, RJ, Xu, ZP & Cai, W (2015). Chelator-free labeling of layered double hydroxide nanoparticles for in vivo PET imaging. Sci Rep 5, 16930.Google Scholar
Singh, KH & Shinde, UA (2011). Chitosan nanoparticles for controlled delivery of brimonidine tartrate to the ocular membrane. Pharmazie 66(8), 594–599.Google Scholar
Sunkireddy, P, Kanwar, RK, Ram, J & Kanwar, JR (2016). Ultra-small algal chitosan ocular nanoparticles with iron-binding milk protein prevents the toxic effects of carbendazim pesticide. Nanomedicine (Lond) 11(5), 495–511.Google Scholar
Tallury, P, Kar, S, Bamrungsap, S, Huang, YF, Tan, W & Santra, S (2009). Ultra-small water-dispersible fluorescent chitosan nanoparticles: Synthesis, characterization and specific targeting. Chem Commun 0(17), 2347–2349.Google Scholar
Tang, S, Huang, Z, Zhang, H, Wang, Y, Hu, Q & Jiang, H (2014). Design and formulation of trimethylated chitosan-graft-poly(epsilon-caprolactone) nanoparticles used for gene delivery. Carbohydr Polym 101, 104–112.Google Scholar
Wang, X, Chi, N & Tang, X (2008). Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. Eur J Pharm Biopharm 70(3), 735–740.Google Scholar
Wu, Y, Yang, W, Wang, C, Hu, J & Fu, S (2005). Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate. Int J Pharm 295(1–2), 235–245.Google Scholar
Yadav, SC, Sunkireddy, P, Tripathi, C & Adholeya, A (2013). Novel chitosan based nanoparticles/ultra nanoparticles and method for the preparation of same. In IN 3060/DEL/2013, India (Ed.), India.Google Scholar
Yang, H, Tyagi, P, Kadam, RS, Holden, CA & Kompella, UB (2012). Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and antiglaucoma effects for four days following one-time topical administration. ACS Nano 6(9), 7595–7606.Google Scholar
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