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Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Research Article

Exploring the Advance Data Mining Tool for Optimization of Nanoparticles Laden in situ Gel for Ocular Drug Delivery

Author(s): Purvi Shah*, Kesha Patel, Kalpana Patel, Vaishali Thakkar, Saloni Dalwadi, Tejal Gandhi and Bhavesh Bhavsar

Volume 19, Issue 1, 2024

Published on: 22 May, 2023

Page: [88 - 102] Pages: 15

DOI: 10.2174/1574885518666230417085251

Price: $65

Abstract

Background: Glaucoma is widely treated using eye drops, but around 95% of the drug is lost by the ocular barrier resulting in low bioavailability. The incorporation of polymeric nanoparticles into mucoadhesive polymer containing in situ gel is generally helpful in the retention of nanoparticles on the eye and improves the efficacy of the formulation.

Objective: The objective of the present investigation has to develop polymeric brinzolamide (BRZ) nanoparticles laden with timolol maleate (TM) in situ gel formulation.

Methods: The optimized BRZ nanoparticles were prepared using PLGA by nanoprecipitation technique utilizing 3 Results: The results of FFD reveal that the optimized condition for drugs to polymer ratio (1:7) containing 0.98 %w/v for poloxamer 188 results in higher entrapment efficiency and drug release with 156.7 nm particle size. The in-situ gel formulation has been prepared using Gelrite (0.5%w/v), and HPMC K4M (0.5%w/v) shows acceptable results with sustained drug release up to 6±0.1 h. The rabbit model's in-vivo pharmacokinetics and pharmacodynamic data showed sustained release of drugs longer than the marketed formulation.

Conclusion: The proposed formulation could successfully deliver therapeutic concentrations in the eye with prolonged resident time and serve as a potential alternative for the treatment of glaucoma.

Keywords: Brinzolamide, timolol maleate, polymeric nanoparticles, full factorial design, nanoparticles laden in situ gel, PLGA.

Graphical Abstract
[1]
Glaucoma: Overview. PubMed Health. Available from: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0088211/ [Assessed on: 12 July 2020].
[2]
Global vision impairment facts. The international agency for the prevention of blindness. Available from: https://www.iapb.org/vision-2020/who-facts/ [Assessed on: 12 July 2020].
[3]
Mahabadi N, Foris LA, Tripathy K. Open-Angle Glaucoma. Treasure Island, FL: StatPearls Publishing 2021.
[4]
Shah PA, Kadikar AS, Gevariya NR, Patel KG. Simultaneous estimation of brinzolamide and timolol maleate using chromatographic methods. Res J Pharm Biol Chem Sci 2014; 5(5): 1010-7.
[5]
Konstas AG, Schmetterer L, Katsanos A, et al. Dorzolamide/timolol fixed combination: Learning from the past and looking toward the future. Adv Ther 2021; 38(1): 24-51.
[http://dx.doi.org/10.1007/s12325-020-01525-5] [PMID: 33108623]
[6]
Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J 2010; 12(3): 348-60.
[http://dx.doi.org/10.1208/s12248-010-9183-3] [PMID: 20437123]
[7]
Chen VSK, Penm JHD. Management of eye disorders and the pharmacist’s role: Eye infections. Encycl Pharm Pract Clin Pharm 2019; 580-97.
[8]
Rawas-Qalaji M, Williams CA. Advances in ocular drug delivery. Curr Eye Res 2012; 37(5): 345-56.
[http://dx.doi.org/10.3109/02713683.2011.652286] [PMID: 22510004]
[9]
Dubashynskaya N, Poshina D, Raik S, Urtti A, Skorik YA. Polysaccharides in ocular drug delivery. Pharmaceutics 2019; 12(1): 22.
[http://dx.doi.org/10.3390/pharmaceutics12010022] [PMID: 31878298]
[10]
Zamboulis A, Nanaki S, Michailidou G, et al. Chitosan and its derivatives for ocular delivery formulations: Recent advances and developments. Polymers 2020; 12(7): 1519.
[http://dx.doi.org/10.3390/polym12071519] [PMID: 32650536]
[11]
Begines B, Ortiz T, Pérez-Aranda M, et al. Polymeric nanoparticles for drug delivery: Recent developments and future prospects. Nanomaterials 2020; 10(7): 1403.
[http://dx.doi.org/10.3390/nano10071403] [PMID: 32707641]
[12]
Elmowafy EM, Tiboni M, Soliman ME. Biocompatibility, biodegradation and biomedical applications of poly(lactic acid)/poly(lactic-co-glycolic acid) micro and nanoparticles. J Pharm Investig 2019; 49(4): 347-80.
[http://dx.doi.org/10.1007/s40005-019-00439-x]
[13]
Cassano R, Di Gioia ML, Trombino S. Gel-based materials for ophthalmic drug delivery. Gels 2021; 7(3): 130.
[http://dx.doi.org/10.3390/gels7030130] [PMID: 34563016]
[14]
Laddha UD, Mahajan HS. An insight to ocular in situ gelling systems. Int J Adv Pharm 2017; 6(2): 31-40.
[15]
Salama HA, Ghorab M, Mahmoud AA, Hady MA. Brinzolamide loaded-polymeric nanoparticles. Curr Sci Int 2016; 5(2): 147-51.
[16]
Kesarla R, Tank T, Vora PA, Shah T, Parmar S, Omri A. Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel. Drug Deliv 2016; 23(7): 2363-70.
[http://dx.doi.org/10.3109/10717544.2014.987333] [PMID: 25579467]
[17]
Abdulaziz A, Ibrahim A, Mohd AK, Aws A. Effect of cryoprotection on particle size stability and preservation of chitosan nanoparticles with and without hyaluronate or alginate coating. Saudi Pharm J 2017; 25(6): 861-7.
[http://dx.doi.org/10.1016/j.jsps.2016.12.008] [PMID: 28951671]
[18]
Ranga S, Jaimini S, Sharma SK, Chauhan BS, Kumar A. A review on design of experiments (DOE). Int J Pharm Chem Sci 2014; 3(1): 216-24.
[19]
Collins LM, Dziak JJ, Kugler KC, Trail JB. Factorial experiments. Am J Prev Med 2014; 47(4): 498-504.
[http://dx.doi.org/10.1016/j.amepre.2014.06.021] [PMID: 25092122]
[20]
Nagarwal RC, Kant S, Singh PN, Maiti P, Pandit JK. Polymeric nanoparticulate system: A potential approach for ocular drug delivery. J Control Release 2009; 136(1): 2-13.
[http://dx.doi.org/10.1016/j.jconrel.2008.12.018] [PMID: 19331856]
[21]
Kabiri M, Kamal SH, Pawar SV, et al. A stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for ocular drug delivery. Drug Deliv Transl Res 2018; 8(3): 484-95.
[http://dx.doi.org/10.1007/s13346-018-0504-x] [PMID: 29508159]
[22]
Ahmed TA, Aljaeid BM. A potential in situ gel formulation loaded with novel fabricated PLGA nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole. Int J Nanomed Sci 2017; 12: 1863-75.
[http://dx.doi.org/10.2147/IJN.S131850] [PMID: 28331311]
[23]
Shah PA, Gevariya NR, Christian JR, et al. Science based development of viscous eye drop of dorzolamide hydrochloride and timolol maleate using full factorial design. Pharm Methods 2018; 9(2): 69-78.
[http://dx.doi.org/10.5530/phm.2018.2.13]
[24]
Anjana VM. Pharm thesis, preparation and evaluation of in-situ gel of timolol maleate and Brinzolamide for the treatment of glaucoma 2015. Available from: https://pubmed.ncbi.nlm.nih.gov/20849349/
[25]
Wen Y, Ban J, Mo Z, et al. A potential nanoparticle-loaded in situ gel for enhanced and sustained ophthalmic delivery of dexamethasone. Nanotechnology 2018; 29(42): 425101.
[http://dx.doi.org/10.1088/1361-6528/aad7da] [PMID: 30074486]
[26]
Katariya DC, Poddar SS. In situ ophthalmic gel of timolol maleate: Formulation rheological studies, in vitro and in vivo evaluation. Indo Am J Pharm Res 2014; 4: 5165-84.
[27]
Saini RR, Saini S, Singh G, Banerjee A. In situ gels- a new trends in ophthalmic drug delivery systems. Int J Pharm Sci Res 2015; 6(5): 886-90.
[28]
Patel N, Thakkar V, Moradiya P, Gandhi T, Gohel M. Optimization of curcumin loaded vaginal in situ hydrogel by box-behnken statistical design for contraception. J Drug Deliv Sci Technol 2015; 29: 55-69.
[http://dx.doi.org/10.1016/j.jddst.2015.06.002]
[29]
Kannan SK, Duraisamy D, Sudhaka Y. Design and statistical optimization of norfloxacin nanoparticulate loaded pH-sensitive droppable gel for ocular drug delivery. Euro J Biomed Pharm Sci 2017; 4: 968-80.
[30]
Mahboobian MM, Foroutan SM, Aboofazeli R. Brinzolamide-loaded nanoemulsions: In vitro release evaluation. Indian J Pharm Sci 2016; 12(3): 75-93.
[31]
FDA Guidance: Guidance for Industry. Bioanalytical method Validation. 2020. Available from: https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Indus- try.pdf [Assessed on: 10 July 2020].
[32]
Slezák P, Bokes P, Námer P, Waczulíková I. Microsoft Excel add-in for the statistical analysis of contingency tables. Int J Innov Educ Res 2014; 2(5): 90-100.
[http://dx.doi.org/10.31686/ijier.vol2.iss5.188]
[33]
Zothanpuii F, Ravindran R, Kanthiah S. A review on stability testing guidelines of pharmaceutical products. Asian J Pharm Clin Res 2020; 13: 3-9.
[http://dx.doi.org/10.22159/ajpcr.2020.v13i10.38848]
[34]
Mirabbasi F, Dorkoosh FA, Moghimi A, Shahsavari S, Babanejad N, Seifirad S. Preparation of mesalamine nanoparticles using a novel polyurethane- chitosan graft copolymer. Pharm Nanotechnol 2017; 5(3): 230-9.
[PMID: 29110631]
[35]
Seifirad S, Karami H, Shahsavari S, Mirabbasi F, Dorkoosh FA. Design and characterization of mesalamine loaded nanoparticles for controlled delivery system. Nanomedicine Res J 2016; 1(2): 97-106.
[http://dx.doi.org/10.7508/nmrj.2016.02.006]
[36]
Shah P, Thakkar V, Anjana V, et al. Exploring of taguchi design in the optimization of Brinzolamide and Timolol Maleate ophthalmic in situ gel used in treatment of glaucoma. Curr Drug Ther 2020; 15(5): 524-42.
[http://dx.doi.org/10.2174/1574885514666190916151506]

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