Research Article
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Posaconazole loaded ocular inserts for antifungal activity

Year 2020, Volume: 1 Issue: 1, 1 - 6, 01.04.2020
https://doi.org/10.37662/jpt.2020.0

Abstract

Corneal and conjunctival infections are common ocular diseases; however, sometimes lead to blindness when neglected. Despite most of the ocular drug delivery systems are in eye drop form, they suffer from poor retention on the ocular surface and low ocular bioavailability leading to unsatisfactory results even with repeated treatment. Therefore, there is a need for more effective drug delivery systems for the ocular application. The present study was carried out to demonstrate that ocular inserts effectively delivers a significant concentration of drug with topical administration for the treatment of fungal infections with the help of extended residence time on the ocular surface. Chitosan-based inserts were prepared by the freeze-drying method. The prepared inserts were evaluated for various parameters. Layered structures were revealed with scanning electron microscopy analyses. Thermal and structural behaviors were analyzed by differential scanning calorimetry and Fourier-transform infrared spectroscopy with nuclear magnetic resonance analyses, respectively. Drug contents were evaluated by a validated HPLC method. In vitro release studies were also performed in simulated tear fluid at 34±1°C for 48 hours. Analyses results revealed that chitosan-based ocular inserts were suitable systems for posaconazole delivery for the treatment of severe ocular fungal infections.

Supporting Institution

Anadolu University Scientific Research Project Foundation

Project Number

BAP No:1901S006

Thanks

The study was financed by Anadolu University Scientific Research Project Foundation (BAP No:1901S006). Authors would like to thank to BIBAM management for SEM, and DOPNA-LAB for FT-IR and 1H-NMR analyses.

References

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  • [2] Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: An overview. World J Pharmacol. (2013); 2: 47-64. https://doi.org/10.5497/wjp.v2.i2.47
  • [3] Krishnaswami V, Kandasamy R, Alagarsamy S, Palanisamy R, Natesan S. Biological macromolecules for ophthalmic drug delivery to treat ocular diseases. Int J Biol Macromol. (2018); 110: 7-16. https://doi.org/10.1016/j.ijbiomac.2018.01.120
  • [4] Kalkancı A, Özdek Ş. Ocular fungal infections. Curr Eye Res. (2011); 36(3): 179-189. https://doi.org/10.3109/02713683.2010.533810
  • [5] Başaran E, Yenilmez E, Berkman MS, Büyükköroğlu G, Yazan Y. Chitosan nanoparticles for ocular delivery of cyclosporine A. J Microencapsul. (2014); 31(1): 49-57. https://doi.org/10.3109/02652048.2013.805839
  • [6] Başaran E, Yazan Y. Ocular application of chitosan. Expert Opin Drug Del. (2012); 9(6):701-712. https://doi.org/10.1517/17425247.2012.681775
  • [7] Franca JR, Foureaux G, Fuscaldi LL, Ribeiro TG, Castilho RO, Yoshid MI, Cardoso VN, Fernandes SOA, Cronemberger S, Nogueira JC, Ferreira AJ, Faraco AAG. Chitosan/hydroxyethyl cellulose inserts for sustained-release of dorzolamide for glaucoma treatment: In vitro and in vivo evaluation. Int J Pharm. (2019); 570: 118662. https://doi.org/10.1016/j.ijpharm.2019.118662
  • [8] Ludwig, A. The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev. (2005); 57: 1595-1639. https://doi.org/10.1016/j.addr.2005.07.005
  • [9] Muxika A, Etxabide A, Uranga J, Guerrero P, de la Caba K. Chitosan as a bioactive polymer: Processing, properties and applications. Int J Biol Macromol. (2017); 105: 1358-1368. https://doi.org/10.1016/j.ijbiomac.2017.07.087
  • [10] Kalantari K, Afifi AM, Jahangirian H, Webster TJ. Biomedical applications of chitosan electrospun nanofibers as a green polymer. Carbohyd Polym. (2019); 207: 588–600. https://doi.org/10.1016/j.carbpol.2018.12.011
  • [11] Dash M, Chiellini F, Ottenbrite RM, Chiellini E. Chitosan-A versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci. (2011); 36: 981-1014. https://doi.org/10.1016/j.progpolymsci.2011.02.001
  • [12] De Campos, AM, Sánchez A, Alonso MJ. Chitosan nanoparticles: A new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm. (2001); 224: 159- 168. https://doi.org/10.1016/S0378-5173(01)00760-8
  • [13] Başaran E, Demirel M, Sırmagül B, Yazan Y. Cyclosporine-A incorporated cationic solid lipid nanoparticles for ocular delivery. J Microencapsul. (2010); 27(1): 37-47. https://doi.org/10.3109/02652040902846883
  • [14] Alonso MH, Sanchez A. The potential of chitosan in ocular drug delivery. J Pharm Pharmacol. (2003); 55: 1451-1463 https://doi.org/10.1211/0022357022476
  • [15] Luo Q, Zhao J, Zhang X, et al. Nanostructured lipid carrier (NLC) coated with Chitosan Oligosaccharides and its potential use in ocular drug delivery system. Int J Pharm. (2011); 403: 185-191. https://doi.org/10.1016/j.ijpharm.2010.10.013
  • [16] Mahmoud AA, El-Feky GS, Kamel R, Awad GEA. Chitosan/ sulfobutylether- cyclodextrin nanoparticles as a potential approach for ocular drug delivery. Int J Pharm. (2011); 413: 229-236. https://doi.org/10.1016/j.ijpharm.2011.04.031
  • [17] Girmenia, C. New generation azole antifungals in clinical investigation. Expert Opin Investig Drugs. (2009); 18(9): 1279-1295. https://doi.org/10.1517/13543780903176407
  • [18] Ping B, Zhu Y, Gao Y, Yue C, Wu B. Second- versus first- generation azoles for antifungal prophylaxis in hematology patients: A systematic review and meta-analysis. Ann Hematol. (2013); 92: 831-839. https://doi.org/10.1007/s00277-013-1693-5
  • [19] Berretta J, Bumgardner, JD, Jennings JA. Lyophilized chitosan sponges. In: Amber Jennings J, Bumgardner JD, editors. Chitosan Based Biomaterials Volume 1. Cambridge:Woodhead Publishing; (2017). p. 239-253. ISBN 978-0-08-100230-8 https://doi.org/10.1016/B978-0-08-100230-8.00010-8
  • [20] Cendejas-Bueno E, Forastiero A, Rodriguez-Tudela JL, Cuenca- Estrella M, Gomez-Lopez A. HPLC/UV or bioassay: two valid methods for Posaconazole quantification in human serum samples. Clin Microbiol Infec. (2012); 18(12): 1229-1235. https://doi.org/10.1111/j.1469-0691.2011.03732.x
  • [21] International Conference on Harmonization (ICH). Guidance for industry: Q2B validation of analytical procedures: methodology. In: Brussels, Belgium: International Conference on Harmonisation. 1996.
  • [22] USP 34 - Dissolution (2011). Retrieved (April 15, 2020) from https:// www.usp.org/sites/default/files/usp/document/harmonization/gen- method/stage_6_monograph_25_feb_2011.pdf
  • [23] Başaran E, Karaca Gençer H, Yenilmez E, Güven UM. Voriconazole incorporated polymeric nanoparticles for ocular application. Lat Am J Pharm. (2017); 36(10): 1983-1994.
  • [24] Crouzier L, Delvallee A, Ducourtieux S, Devoille L, Tromas C, Feltin N. A new method for measuring nanoparticle diameter from a set of SEM images using a remarkable point. Ultramicroscopy. (2019); 207: 112847. https://doi.org/10.1016/j.ultramic.2019.112847
  • [25] Jaber N, Aiedeh K. Sorption behavior and release kinetics of iron (II) ions by oleoyl chitosan polymeric nanoparticles. J Drug Deliv Sci Tec. (2019); 54: 101354. https://doi.org/10.1016/j.jddst.2019.101354
  • [26] Sur S, Rathore A, Dave V, Reddy KR, Chouhan RS, Sadhu V. Recent developments in functionalized polymer nanoparticles for efficient drug delivery system. Nano-Structures & Nano-Objects. (2019); 20: 100397. https://doi.org/10.1016/j.nanoso.2019.100397
  • [27] Başaran E, Şenel B, Yurtdaş Kırımlıoğlu, G, Güven UM, Yazan Y. Ornidazole incorporated chitosan nanoparticles for ocular application. Lat Am J Pharm. (2015); 34(6): 1180-1188.
  • [28] TangP,WangL,MaX,XuK,XiongX,LiaoX,LiH. Characterization and in vitro evaluation of the complexes of posaconazole with β- and 2,6-di-o-methyl-β-cyclodextrin. AAPS Pharm Sci Tech. (2017); 18(1): 104-114. https://doi.org/10.1208/s12249-016-0497-z
  • [29] Başaran E, Ocular application of dirithromycin incorporated polymeric nanoparticles: An in vitro evaluation. Turk J Pharm Sci. (2017); 14(2): 191-200. https://doi.org/10.4274/tjps.69855
  • [30] Rathod LV, Kapadia R, Sawant KK. A novel nanoparticle impregnated ocular insert for enhanced bioavailability to posterior segment of eye: In vitro, in vivo and stability studies. Mat Sci Eng C. (2017); 71: 529-540. https://doi.org/10.1016/j.msec.2016.10.017
  • [31] Posaconazole. Retrieved (April 15, 2020) from https://www.drugbank.ca/drugs/DB01263
  • [32] Lee H, Xu G, Kharaghani D, Nishino M, Song KH, Lee JS, Kim IS. Electrospun tri-layered zein/PVP-GO/zein nanofiber mats for providing biphasic drug release profiles. Int J Pharm. (2017); 531: 101-107. https://doi.org/10.1016/j.ijpharm.2017.08.081
Year 2020, Volume: 1 Issue: 1, 1 - 6, 01.04.2020
https://doi.org/10.37662/jpt.2020.0

Abstract

Project Number

BAP No:1901S006

References

  • [1] Chaudhari P, Ghate VM, Lewis SA. Supramolecular cyclodextrin complex: Diversity, safety, and applications in ocular therapeutics. Exp Eye Res. (2019); 189: 107829. https://doi.org/10.1016/j.exer.2019.107829
  • [2] Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: An overview. World J Pharmacol. (2013); 2: 47-64. https://doi.org/10.5497/wjp.v2.i2.47
  • [3] Krishnaswami V, Kandasamy R, Alagarsamy S, Palanisamy R, Natesan S. Biological macromolecules for ophthalmic drug delivery to treat ocular diseases. Int J Biol Macromol. (2018); 110: 7-16. https://doi.org/10.1016/j.ijbiomac.2018.01.120
  • [4] Kalkancı A, Özdek Ş. Ocular fungal infections. Curr Eye Res. (2011); 36(3): 179-189. https://doi.org/10.3109/02713683.2010.533810
  • [5] Başaran E, Yenilmez E, Berkman MS, Büyükköroğlu G, Yazan Y. Chitosan nanoparticles for ocular delivery of cyclosporine A. J Microencapsul. (2014); 31(1): 49-57. https://doi.org/10.3109/02652048.2013.805839
  • [6] Başaran E, Yazan Y. Ocular application of chitosan. Expert Opin Drug Del. (2012); 9(6):701-712. https://doi.org/10.1517/17425247.2012.681775
  • [7] Franca JR, Foureaux G, Fuscaldi LL, Ribeiro TG, Castilho RO, Yoshid MI, Cardoso VN, Fernandes SOA, Cronemberger S, Nogueira JC, Ferreira AJ, Faraco AAG. Chitosan/hydroxyethyl cellulose inserts for sustained-release of dorzolamide for glaucoma treatment: In vitro and in vivo evaluation. Int J Pharm. (2019); 570: 118662. https://doi.org/10.1016/j.ijpharm.2019.118662
  • [8] Ludwig, A. The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev. (2005); 57: 1595-1639. https://doi.org/10.1016/j.addr.2005.07.005
  • [9] Muxika A, Etxabide A, Uranga J, Guerrero P, de la Caba K. Chitosan as a bioactive polymer: Processing, properties and applications. Int J Biol Macromol. (2017); 105: 1358-1368. https://doi.org/10.1016/j.ijbiomac.2017.07.087
  • [10] Kalantari K, Afifi AM, Jahangirian H, Webster TJ. Biomedical applications of chitosan electrospun nanofibers as a green polymer. Carbohyd Polym. (2019); 207: 588–600. https://doi.org/10.1016/j.carbpol.2018.12.011
  • [11] Dash M, Chiellini F, Ottenbrite RM, Chiellini E. Chitosan-A versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci. (2011); 36: 981-1014. https://doi.org/10.1016/j.progpolymsci.2011.02.001
  • [12] De Campos, AM, Sánchez A, Alonso MJ. Chitosan nanoparticles: A new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm. (2001); 224: 159- 168. https://doi.org/10.1016/S0378-5173(01)00760-8
  • [13] Başaran E, Demirel M, Sırmagül B, Yazan Y. Cyclosporine-A incorporated cationic solid lipid nanoparticles for ocular delivery. J Microencapsul. (2010); 27(1): 37-47. https://doi.org/10.3109/02652040902846883
  • [14] Alonso MH, Sanchez A. The potential of chitosan in ocular drug delivery. J Pharm Pharmacol. (2003); 55: 1451-1463 https://doi.org/10.1211/0022357022476
  • [15] Luo Q, Zhao J, Zhang X, et al. Nanostructured lipid carrier (NLC) coated with Chitosan Oligosaccharides and its potential use in ocular drug delivery system. Int J Pharm. (2011); 403: 185-191. https://doi.org/10.1016/j.ijpharm.2010.10.013
  • [16] Mahmoud AA, El-Feky GS, Kamel R, Awad GEA. Chitosan/ sulfobutylether- cyclodextrin nanoparticles as a potential approach for ocular drug delivery. Int J Pharm. (2011); 413: 229-236. https://doi.org/10.1016/j.ijpharm.2011.04.031
  • [17] Girmenia, C. New generation azole antifungals in clinical investigation. Expert Opin Investig Drugs. (2009); 18(9): 1279-1295. https://doi.org/10.1517/13543780903176407
  • [18] Ping B, Zhu Y, Gao Y, Yue C, Wu B. Second- versus first- generation azoles for antifungal prophylaxis in hematology patients: A systematic review and meta-analysis. Ann Hematol. (2013); 92: 831-839. https://doi.org/10.1007/s00277-013-1693-5
  • [19] Berretta J, Bumgardner, JD, Jennings JA. Lyophilized chitosan sponges. In: Amber Jennings J, Bumgardner JD, editors. Chitosan Based Biomaterials Volume 1. Cambridge:Woodhead Publishing; (2017). p. 239-253. ISBN 978-0-08-100230-8 https://doi.org/10.1016/B978-0-08-100230-8.00010-8
  • [20] Cendejas-Bueno E, Forastiero A, Rodriguez-Tudela JL, Cuenca- Estrella M, Gomez-Lopez A. HPLC/UV or bioassay: two valid methods for Posaconazole quantification in human serum samples. Clin Microbiol Infec. (2012); 18(12): 1229-1235. https://doi.org/10.1111/j.1469-0691.2011.03732.x
  • [21] International Conference on Harmonization (ICH). Guidance for industry: Q2B validation of analytical procedures: methodology. In: Brussels, Belgium: International Conference on Harmonisation. 1996.
  • [22] USP 34 - Dissolution (2011). Retrieved (April 15, 2020) from https:// www.usp.org/sites/default/files/usp/document/harmonization/gen- method/stage_6_monograph_25_feb_2011.pdf
  • [23] Başaran E, Karaca Gençer H, Yenilmez E, Güven UM. Voriconazole incorporated polymeric nanoparticles for ocular application. Lat Am J Pharm. (2017); 36(10): 1983-1994.
  • [24] Crouzier L, Delvallee A, Ducourtieux S, Devoille L, Tromas C, Feltin N. A new method for measuring nanoparticle diameter from a set of SEM images using a remarkable point. Ultramicroscopy. (2019); 207: 112847. https://doi.org/10.1016/j.ultramic.2019.112847
  • [25] Jaber N, Aiedeh K. Sorption behavior and release kinetics of iron (II) ions by oleoyl chitosan polymeric nanoparticles. J Drug Deliv Sci Tec. (2019); 54: 101354. https://doi.org/10.1016/j.jddst.2019.101354
  • [26] Sur S, Rathore A, Dave V, Reddy KR, Chouhan RS, Sadhu V. Recent developments in functionalized polymer nanoparticles for efficient drug delivery system. Nano-Structures & Nano-Objects. (2019); 20: 100397. https://doi.org/10.1016/j.nanoso.2019.100397
  • [27] Başaran E, Şenel B, Yurtdaş Kırımlıoğlu, G, Güven UM, Yazan Y. Ornidazole incorporated chitosan nanoparticles for ocular application. Lat Am J Pharm. (2015); 34(6): 1180-1188.
  • [28] TangP,WangL,MaX,XuK,XiongX,LiaoX,LiH. Characterization and in vitro evaluation of the complexes of posaconazole with β- and 2,6-di-o-methyl-β-cyclodextrin. AAPS Pharm Sci Tech. (2017); 18(1): 104-114. https://doi.org/10.1208/s12249-016-0497-z
  • [29] Başaran E, Ocular application of dirithromycin incorporated polymeric nanoparticles: An in vitro evaluation. Turk J Pharm Sci. (2017); 14(2): 191-200. https://doi.org/10.4274/tjps.69855
  • [30] Rathod LV, Kapadia R, Sawant KK. A novel nanoparticle impregnated ocular insert for enhanced bioavailability to posterior segment of eye: In vitro, in vivo and stability studies. Mat Sci Eng C. (2017); 71: 529-540. https://doi.org/10.1016/j.msec.2016.10.017
  • [31] Posaconazole. Retrieved (April 15, 2020) from https://www.drugbank.ca/drugs/DB01263
  • [32] Lee H, Xu G, Kharaghani D, Nishino M, Song KH, Lee JS, Kim IS. Electrospun tri-layered zein/PVP-GO/zein nanofiber mats for providing biphasic drug release profiles. Int J Pharm. (2017); 531: 101-107. https://doi.org/10.1016/j.ijpharm.2017.08.081
There are 32 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Research Articles
Authors

Kadir Aykaç

Evrim Yenilmez 0000-0002-7979-0089

Müzeyyen Demirel

Ebru Başaran 0000-0003-2104-2069

Project Number BAP No:1901S006
Publication Date April 1, 2020
Submission Date March 6, 2020
Acceptance Date May 14, 2020
Published in Issue Year 2020 Volume: 1 Issue: 1

Cite

APA Aykaç, K., Yenilmez, E., Demirel, M., Başaran, E. (2020). Posaconazole loaded ocular inserts for antifungal activity. Journal of Pharmaceutical Technology, 1(1), 1-6. https://doi.org/10.37662/jpt.2020.0

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