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Current Nanomedicine

Editor-in-Chief

ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

Short Communication

Dexamethasone Loaded Electrospun Nanocomposite Ocular Insert: In-vitro Drug Release and Mechanical Assessment

Author(s): Rishabh Agarwal, Dhwani Rana, Sagar Salave and Derajram Benival*

Volume 12, Issue 2, 2022

Published on: 23 August, 2022

Page: [150 - 158] Pages: 9

DOI: 10.2174/2468187312666220806133901

Price: $65

Abstract

Background: Dexamethasone is currently available as a suspension for the treatment of anterior ocular inflammatory diseases that are given through eye drops. However, less than 5% of the drug gets absorbed when applied topically as eye drops. The major portion of administered drug either comes out from the eye or gets subjected to nasolacrimal drainage, resulting in poor bioavailability.

Objective: The present study aims to develop a polymeric ocular insert containing dexamethasone as a drug by employing the electrospinning technique.

Methods: Dexamethasone (0.1% w/v) loaded electrospun sheet was also made using 10% w/v EC: HPMC: PEO (60:20:20) in a solvent system of ethanol: water (90:10) at optimized electrospinning parameters of 12kV with a flow rate of 0.8mL/hr and distance of 20 cm between tip and collector.

Results: The prepared nanocomposite insert was characterized for DSC and FTIR-ATR spectroscopy, revealing no physical-chemical interaction between drugs with polymers. The thickness of the electrospun sheet was found to be 270±0.02 μm, and % the drug content was found to be 0.43±0.01% w/w. The release profile showed that around 95% drug was released in 48 hrs. This release profile showed that the prepared drug-loaded electrospun ocular insert is best suitable for once-a-day delivery. Assessment of mechanical properties like young’s modulus, tensile strength, and % elongation showed that the prepared insert could be handled easily without any breakage or damage.

Conclusion: Upon delivery in the conjunctival sac, the developed insert is best suitable for once-aday delivery. The developed electrospun insert, consisting of a unique polymer composite of biodegradable polymers, avails the benefits of nanofibers imparting prolonged release, and this novel formulation overcomes the limitations of conventional therapies. This reduces the dosing frequency and improves patient compliance.

Keywords: Dexamethasone, ocular insert, electrospinning, nanocomposite, ocular drug delivery, conjunctival sac.

Graphical Abstract

[1]
Hiraoka, T.; Yamamoto, T.; Okamoto, F.; Oshika, T. Time course of changes in ocular wavefront aberration after administration of eye ointment. Eye (Lond.), 2012, 26(10), 1310-1317.
[http://dx.doi.org/10.1038/eye.2012.142] [PMID: 22814810]
[2]
Gote, V.; Sikder, S.; Sicotte, J.; Pal, D. Ocular drug delivery: Present innovations and future challenges. J. Pharmacol. Exp. Ther., 2019, 370(3), 602-624.
[http://dx.doi.org/10.1124/jpet.119.256933] [PMID: 31072813]
[3]
Falavarjani, K.G.; Nguyen, Q.D. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: A review of literature. Eye (Lond.), 2013, 27(7), 787-794.
[http://dx.doi.org/10.1038/eye.2013.107] [PMID: 23722722]
[4]
Gorantla, S.; Rapalli, V.K.; Waghule, T. Nanocarriers for ocular drug delivery: Current status and translational opportunity. RSC Advances, 2020, 10(46), 27835-27855.
[http://dx.doi.org/10.1039/D0RA04971A] [PMID: 35516960]
[5]
Gaudana, R.; Ananthula, H.K.; Parenky, A.; Mitra, A.K. Ocular drug delivery. AAPS J., 2010, 12(3), 348-360.
[http://dx.doi.org/10.1208/s12248-010-9183-3] [PMID: 20437123]
[6]
Chang, M.C.; Luo, T.Y.; Huang, C.Y.; Peng, C.L.; Chen, K.Y.; Yeh, L.K. The new ophthalmic formulation for infection control by combining collagen/gelatin/alginate biomaterial with liposomal chloramphenicol. Biomed. Phys. Eng. Express, 2020, 6(4), 045017.
[http://dx.doi.org/10.1088/2057-1976/ab97a2] [PMID: 33444277]
[7]
De, T.K.; Rodman, D.J.; Holm, B.A.; Prasad, P.N.; Bergey, E.J. Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery. J. Microencapsul., 2003, 20(3), 361-374.
[http://dx.doi.org/10.3109/02652040309178075] [PMID: 12881116]
[8]
Prata, A.I.; Coimbra, P.; Pina, M.E. Preparation of dexamethasone ophthalmic implants: A comparative study of in vitro release profiles. Pharm. Dev. Technol., 2018, 23(3), 218-224.
[http://dx.doi.org/10.1080/10837450.2017.1306560] [PMID: 28300463]
[9]
Hamdi, Y.; Lallemand, F.; Benita, S. Drug-loaded nanocarriers for back-of-the-eye diseases- formulation limitations. J. Drug Deliv. Sci. Technol., 2015, 30, 331-341.
[http://dx.doi.org/10.1016/j.jddst.2015.09.010]
[10]
Bhattarai, R.S.; Das, A.; Alzhrani, R.M.; Kang, D.; Bhaduri, S.B.; Boddu, S.H.S. Comparison of electrospun and solvent cast polylactic acid (PLA)/poly(vinyl alcohol) (PVA) inserts as potential ocular drug delivery vehicles. Mater. Sci. Eng. C, 2017, 77, 895-903.
[http://dx.doi.org/10.1016/j.msec.2017.03.305] [PMID: 28532107]
[11]
Omer, S.; Zelkó, R. A systematic review of drug-loaded electrospun nanofiber-based ophthalmic inserts. Pharmaceutics, 2021, 13(10), 1637.
[http://dx.doi.org/10.3390/pharmaceutics13101637] [PMID: 34683930]
[12]
Patil, S.S.; Bade, A.; Tagalpallewar, A. Design, optimization and pharmacodynamic comparison of dorzolamide hydrochloride soluble ocular drug insert prepared by using 32 factorial design. J. Drug Deliv. Sci. Technol., 2018, 46, 138-147.
[http://dx.doi.org/10.1016/j.jddst.2018.05.010]
[13]
FDA. FDA. Center for drug evaluation and research approval package for: Application number: 208742Orig1s000., 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208742Orig1s000Approv.pdf
[14]
Lacrisert® (hydroxypropyl cellulose ophthalmic insert). 2007. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018771s017lbl.pdf
[15]
Li, M.; Mondrinos, M.J.; Gandhi, M.R.; Ko, F.K.; Weiss, A.S.; Lelkes, P.I. Electrospun protein fibers as matrices for tissue engineering. Biomaterials, 2005, 26(30), 5999-6008.
[http://dx.doi.org/10.1016/j.biomaterials.2005.03.030] [PMID: 15894371]
[16]
Zeng, J.; Xu, X.; Chen, X. Biodegradable electrospun fibers for drug delivery. J. Control. Release, 2003, 92(3), 227-231.
[http://dx.doi.org/10.1016/S0168-3659(03)00372-9] [PMID: 14568403]
[17]
Khil, M.S.; Cha, D.I.; Kim, H.Y.; Kim, I.S.; Bhattarai, N. Electrospun nanofibrous polyurethane membrane as wound dressing. J. Biomed. Mater. Res. B Appl. Biomater., 2003, 67(2), 675-679.
[http://dx.doi.org/10.1002/jbm.b.10058] [PMID: 14598393]
[18]
Polat, HK Bozdağ Pehlivan S, Özkul C, et al. Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation. Int. J. Pharm., 2020, 585, 119552.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119552] [PMID: 32569814]
[19]
Lancina, M.G., III; Singh, S.; Kompella, U.B.; Husain, S.; Yang, H. Fast dissolving dendrimer nanofiber mats as alternative to eye drops for more efficient antiglaucoma drug delivery. ACS Biomater. Sci. Eng., 2017, 3(8), 1861-1868.
[http://dx.doi.org/10.1021/acsbiomaterials.7b00319] [PMID: 29152562]
[20]
FDA. FDA, CDER. Paediatric cardiac Maxidex® (dexamethasone ophthalmic suspension) 0.1% sterile; , 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/013422s046lbl.pdf
[21]
Lee, A.; Blair, H.A. Dexamethasone intracanalicular insert: A review in treating post-surgical ocular pain and inflammation. Drugs, 2020, 80(11), 1101-1108.
[http://dx.doi.org/10.1007/s40265-020-01344-6] [PMID: 32588339]
[22]
Cronau, H.; Kankanala, R.R.; Mauger, T. Diagnosis and management of red eye in primary care. Am. Fam. Physician, 2010, 81(2), 137-144.
[PMID: 20082509]
[23]
Saincher, S.S.; Gottlieb, C. Ozurdex (dexamethasone intravitreal implant) for the treatment of intermediate, posterior, and panuveitis: A systematic review of the current evidence. J. Ophthalmic Inflamm. Infect., 2020, 10(1), 1.
[http://dx.doi.org/10.1186/s12348-019-0189-4] [PMID: 31925591]
[24]
Nayak, K.; Misra, M. PEGylated microemulsion for dexamethasone delivery to posterior segment of eye. J. Biomater. Sci. Polym. Ed., 2020, 31(8), 1071-1090.
[http://dx.doi.org/10.1080/09205063.2020.1740964] [PMID: 32149562]
[25]
Thakkar, S.; More, N.; Sharma, D.; Kapusetti, G.; Kalia, K.; Misra, M. Fast dissolving electrospun polymeric films of anti-diabetic drug repaglinide: Formulation and evaluation. Drug Dev. Ind. Pharm., 2019, 45(12), 1921-1930.
[http://dx.doi.org/10.1080/03639045.2019.1680994] [PMID: 31625774]
[26]
D’Souza, S. A review of in vitro drug release test methods for nano-sized dosage forms. Adv Pharm, 2014, 2014, 1-12.
[http://dx.doi.org/10.1155/2014/304757]
[27]
Santos, W.M.; Nóbrega, F.P.; Andrade, J.C.; Almeida, L.F.; Conceição, M.M.; Medeiros, A.C.D. Pharmaceutical compatibility of dexamethasone with excipients commonly used in solid oral dosage forms. J. Therm. Anal. Calorim., 2020, 145(2), 361-378.
[http://dx.doi.org/10.1007/s10973-020-09753-1]
[28]
Di Prima, G.; Licciardi, M.; Carfì Pavia, F.; Lo Monte, A.I.; Cavallaro, G.; Giammona, G. Microfibrillar polymeric ocular inserts for triamcinolone acetonide delivery. Int. J. Pharm., 2019, 567, 118459.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118459] [PMID: 31247275]
[29]
Qureshi, J.; Iqbal, F.M.; Hussain, F.; Ijaz, H.; Aamir, M.F.; Afzal, M. Fabrication and evaluation of olopatadine hydrochloride ocular inserts. J. Plast. Film Sheeting, 2020, 36(3), 243-259.
[http://dx.doi.org/10.1177/8756087920911423]
[30]
Grimaudo, M.A.; Concheiro, A.; Alvarez-Lorenzo, C. Crosslinked hyaluronan electrospun nanofibers for ferulic acid ocular delivery. Pharmaceutics, 2020, 12(3), 274.
[http://dx.doi.org/10.3390/pharmaceutics12030274] [PMID: 32192007]
[31]
Lisa Land, D.; Benjamin, W.J. Sizes and shapes of conjunctival inserts. Int. Contact Lens Clin., 1994, 21(11–12), 212-217.
[http://dx.doi.org/10.1016/0892-8967(94)90053-1]
[32]
Che, X.; Xue, J.; Zhang, J.; Yang, X.; Wang, L. One-step preparation of ibuprofen fast- and sustained-release formulation by electrospinning with improved efficacy and reduced side effect. Pharm. Dev. Technol., 2020, 25(6), 659-665.
[http://dx.doi.org/10.1080/10837450.2020.1728773] [PMID: 32067550]
[33]
Yu, D.G.; Wang, X.; Li, X.Y.; Chian, W.; Li, Y.; Liao, Y.Z. Electrospun biphasic drug release polyvinylpyrrolidone/ethyl cellulose core/sheath nanofibers. Acta Biomater., 2013, 9(3), 5665-5672.
[http://dx.doi.org/10.1016/j.actbio.2012.10.021] [PMID: 23099302]
[34]
Franca, J.R.; Foureaux, G.; Fuscaldi, L.L. Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: In vitro and in vivo evaluation. PLoS One, 2014, 9(4), e95461.
[http://dx.doi.org/10.1371/journal.pone.0095461] [PMID: 24788066]

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