Nasal in situ gels as a drug delivery system: An overview of literature and clinical studies

Yavuz Selim Çelik; Büşra Örenli; Mazen Al-mohaya; Burcu Mesut; Yıldız Özsoy

Nasal in situ gels as a drug delivery system: An overview of literature and clinical studies

Abstract

There are various ways to deliver drugs and each one has its ups and downs depending on the purpose of use and the patients themselves. And among these drug delivery systems, the intranasal path stands out as one of the more exciting and challenging ones. Despite being perhaps the most commonly used path of delivery, the oral route is subject to facing various roadblocks in terms of efficacy and bioavailability, requiring a certain amount of dosage and synergy from the active pharmaceutical ingredient that is being used to be effective. When said active pharmaceutical ingredient is ineffective via the oral route, has to be given in small doses, or has to enter circulation quickly to manifest its effects, it inevitably falls out of favor. In its place, the intranasal route can act as a viable substitute. Although there are several methods to formulate intranasal drugs, naturally, the intranasal route possesses advantages and disadvantages of its own. Thus, in situ gel systems have emerged as a favorable preference among these formulation methods. Possessing the upsides of not only gels but solutions as well, the in situ gel systems effectively address and solve some of the disadvantages posed by intranasal drug delivery systems. This review article aims to provide a general understanding of intranasal drug delivery systems and in situ gels, both separately and together as a combination, while underlining the importance of each and also providing examples from existing literature to display their range of applications.

Keywords

References

[1] Laffleur F, Bauer B. Progress in nasal drug delivery systems. Int. J. Pharm. 2021; 607: 120994. https://doi.org/10.1016/j.ijpharm.2021.120994
[2] Agrawal M, Saraf S, Saraf S, Dubey SK, Puri A, Gupta U, Kesharwani P, Ravichandiran V, Kumar P, Naidu VGM, Murty US, Ajazuddin, Alexander A. Stimuli-responsive In situ gelling system for nose-to-brain drug delivery. J. Contr. Release. 2020; 327: 235-65. https://doi.org/10.1016/j.jconrel.2020.07.044
[3] Karavasili C, Fatouros DG. Smart materials: in situ gel-forming systems for nasal delivery. Drug Discov. Today. 2016; 21(1): 157-66. https://doi.org/10.1016/j.drudis.2015.10.016
[4] Beule AG. Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses. GMS Curr. Top. Otorhinolaryngol. Head Neck Surg. 2010: 9. https://doi.org/10.3205/cto000071
[5] Sun Y, Li L, Xie H, Wang Y, Gao S, Zhang L, Bo F, Yang S, Feng A. Primary studies on construction and evaluation of ion-sensitive in situ gel loaded with paeonol-solid lipid nanoparticles for intranasal drug delivery. Int. J. Nanomed. 2020: 3137-60. https://doi.org/10.2147/IJN.S247935
[6] Chen Y, Cheng G, Hu R, Chen S, Lu W, Gao S, Xia H, Wang B, Sun C, Nie X, Shen Q, Fang W. A nasal temperature and pH dual-responsive in situ gel delivery system based on microemulsion of huperzine A: Formulation, evaluation, and in vivo pharmacokinetic study. Aaps Pharmscitech. 2019; 20: 1-2. https://doi.org/10.1208/s12249-019-1513-x
[7] Abdelnabi DM, Abdallah MH, Elghamry HA. Buspirone hydrochloride loaded in situ nanovesicular gel as an anxiolytic nasal drug delivery system: In vitro and animal studies. AAPS PharmSciTech. 2019; 20: 1-4. https://doi.org/10.1208/s12249-018-1211-0
[8] Crowe TP, Hsu WH. Evaluation of recent intranasal drug delivery systems to the central nervous system. Pharmaceutics. 2022; 14(3): 629. https://doi.org/10.3390/pharmaceutics14030629

[9] Malviya V, Ladhake V, Gajbiye K, Satao J, Tawar M. Design and characterization of phase transition system of zolmitriptan hydrochloride for nasal drug delivery system Int. J. Pharm. Sci. Nanotechnol. (IJPSN). 2020; 13(3): 4942-51. https://doi.org/10.37285/ijpsn.2020.13.3.8
[10] Ourani-Pourdashti S, Mirzaei E, Heidari R, Ashrafi H, Azadi A. Preparation and evaluation of niosomal chitosan-based in situ gel formulation for direct nose-to-brain methotrexate delivery. Int. J. Biol. Macromol. 2022; 213: 1115-26. https://doi.org/10.1016/j.ijbiomac.2022.06.031
[11] Verekar RR, Gurav SS, Bolmal U. Thermosensitive mucoadhesive in situ gel for intranasal delivery of Almotriptan malate: Formulation, characterization, and evaluation. J. Drug Deliv. Sci. Technol. 2020; 58: 101778. https://doi.org/10.1016/j.jddst.2020.101778
[12] Bekhet MA, Ali AA, Kharshoum RM, El-Ela FIA, Salem HF. Intranasal niosomal in situ gel as a novel strategy for improving citicoline efficacy and brain delivery in treatment of epilepsy: In vitro and ex vivo characterization and in vivo pharmacodynamics investigation. J. Pharm. Sci. 2022; 111(8): 2258-69. https://doi.org/10.1016/j.xphs.2022.02.012
[13] Aulton ME, Taylor K, editors. Aulton's pharmaceutics: the design and manufacture of medicines. Elsevier Health Sciences; 2013
[14] Ghori MU, Mahdi MH, Smith AM, Conway BR. Nasal drug delivery systems: an overview. Am. J. Pharmacol. Sci. 2015; 3(5): 110-9.
[15] Keller LA, Merkel O, Popp A. Intranasal drug delivery: Opportunities and toxicologic challenges during drug development. Drug Deliv. Transl. Res. 2021: 1-23. https://doi.org/10.1007/s13346-020-00891-5
[16] Dreamstime: Stock Photos & Images, Vectors, Video & Audio. https://www.dreamstime.com/stock-image-nose-anatomy-image29506621 (accessed on 22 April 2023)
[17] Tai J, Han M, Lee D, Park IH, Lee SH, Kim TH. Different methods and formulations of drugs and vaccines for nasal administration. Pharmaceutics. 2022; 14(5): 1073. https://doi.org/10.3390/pharmaceutics14051073
[18] Shah B. Microemulsion as a promising carrier for nose to brain delivery: Journey since last decade. J. Pharm. Investig. 2021: 1-24. https://doi.org/10.1007/s40005-021-00528-w
[19] McGuckin MB, Wang J, Ghanma R, Qin N, Palma SD, Donnelly RF, Paredes AJ. Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes. J. Contr. Release. 2022; 345: 334-353. https://doi.org/10.1016/j.jconrel.2022.03.012
[20] Vasantha PV, Sherafudeen SP, Rahamathulla M, Mathew ST, Murali S, Alshehri S, Shakeel F, Alam P, Sirhan AY, Iyer BAN. Combination of Cellulose Derivatives and Chitosan-Based Polymers to Investigate the Effect of Permeation Enhancers Added to In situ Nasal Gels for the Controlled Release of Loratadine and Chlorpheniramine. Polymers. 2023; 15(5): 1206. https://doi.org/10.3390/polym15051206
[21] Xu J, Tao J, Wang J. Design and application in delivery system of intranasal antidepressants. Front. Bioeng. Biotechnol. 2020; 8: 626882. https://doi.org/10.3389/fbioe.2020.626882
[22] Vigani B, Rossi S, Sandri G, Bonferoni MC, Caramella CM, Ferrari F. Recent advances in the development of in situ gelling drug delivery systems for non-parenteral administration routes. Pharmaceutics. 2020; 12(9): 859. https://doi.org/10.3390/pharmaceutics12090859
[23] Makwana SB, Patel VA, Parmar SJ. Development and characterization of in situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride. Results Pharma Sci. 2016; 6: 1-6. https://doi.org/10.1016/j.rinphs.2015.06.001
[24] Mohanty D, Bakshi V, Simharaju N, Haque MA, Sahoo CK. A review on in situ gel: a novel drug delivery system. Int. J. Pharm. Sci. Rev. Res. 2018; 50(1): 175-81.
[25] Chatterjee S, Hui PCI. Review of applications and future prospects of stimuli-responsive hydrogel based on thermo-responsive biopolymers in drug delivery systems. Polymers. 2021; 13(13): 2086. https://doi.org/10.3390/polym13132086
[26] Uppuluri CT, Ravi PR, Dalvi AV, Shaikh SS, Kale SR. Piribedil loaded thermo-responsive nasal in situ gelling system for enhanced delivery to the brain: formulation optimization, physical characterization, and in vitro and in vivo evaluation. Drug Deliv. Transl. Res. 2021; 11: 909-26. https://doi.org/10.1007/s13346-020-00800-w
[27] Sharma D, Atassi F, Cook S, Marden S, Wang J, Xue A, Wagner DJ, Zhang G, Yang W. Experimental design, development and evaluation of extended release subcutaneous thermo-responsive in situ gels for small molecules in drug discovery. Pharm. Dev. Technol. 2021; 26(10): 1079-89. https://doi.org/10.1080/10837450.2021.1985519
[28] Wang F, Liu Z, Zou LB, Xie R, Ju XJ, Wang W, Pan DW, Chu LY. A universal model for describing responsive performances of both positively and negatively responsive smart gating membranes J. Membr. Sci. 2023; 668: 121235. https://doi.org/10.1016/j.memsci.2022.121235
[29] Chen IC, Su CY, Chen PY, Hoang TC, Tsou YS, Fang HW. Investigation and characterization of factors affecting rheological properties of poloxamer-based thermo-sensitive hydrogel. Polymers. 2022; 14(24): 5353. https://doi.org/10.3390/polym14245353
[30] Salem HF, Kharshoum RM, Abou-Taleb HA, Naguib DM. Nanosized transferosome-based intranasal in situ gel for brain targeting of resveratrol: formulation, optimization, in vitro evaluation, and in vivo pharmacokinetic study. Aaps pharmscitech. 2019; 20: 1-4. https://doi.org/10.1208/s12249-019-1353-8
[31] Rudko M, Urbaniak T, Musiał W. Recent developments in ion-sensitive systems for pharmaceutical applications. Polymers. 2021; 13(10): 1641. https://doi.org/10.3390/polym13101641
[32] Kolawole OM, Cook MT. In situ gelling drug delivery systems for topical drug delivery. Eur. J. Pharm. Biopharm. 2023 Jan 13. https://doi.org/10.1016/j.ejpb.2023.01.007
[33] Li D, editor. Encyclopedia of microfluidics and nanofluidics. Springer Science & Business Media; 2008.
[34] Kouchak M, Mahmoodzadeh M, Farrahi F. Designing of a pH-triggered carbopol®/HPMC in situ gel for ocular delivery of dorzolamide HCl: in vitro, in vivo, and ex vivo evaluation. AAPS PharmSciTech. 2019; 20: 1-8. https://doi.org/10.1208/s12249-019-1431-y
[35] Ma Q, Luo R, Zhang H, Dai M, Bai L, Fei Q, Lei F, He N. Design, characterization, and application of a pH-triggered in situ gel for ocular delivery of vinpocetine. AAPS PharmSciTech. 2020; 21: 1-1. https://doi.org/10.1208/s12249-020-01791-0
[36] Jain P, Jaiswal CP, Mirza MA, Anwer MK, Iqbal Z. Preparation of levofloxacin loaded in situ gel for sustained ocular delivery: in vitro and ex vivo evaluations. Drug Dev. Ind. Pharm. 2020; 46(1): 50-6. https://doi.org/10.1080/03639045.2019.1698598
[37] Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RSR. Thermoreversible-mucoadhesive gel for nasal delivery of sumatriptan. AAPS pharmscitech. 2006; 7: E80-6. https://doi.org/10.1208/pt070367
[38] Kammoun AK, Khedr A, Hegazy MA, Almalki AJ, Hosny KM, Abualsunun WA, Murshid SSA, Bakhaidar RB. Formulation, optimization, and nephrotoxicity evaluation of an antifungal in situ nasal gel loaded with voriconazole‒clove oil transferosomal nanoparticles. Drug Deliv. 2021; 28(1): 2229-40. https://doi.org/10.1080/10717544.2021.1992040
[39] Verekar RR, Gurav SS, Bolmal U. Thermosensitive mucoadhesive in situ gel for intranasal delivery of Almotriptan malate: Formulation, characterization, and evaluation. J. Drug Deliv. Sci. Technol. 2020; 58: 101778. https://doi.org/10.1016/j.jddst.2020.101778
[40] Zaki NM, Awad GA, Mortada ND, ElHady SSA. Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur. J. Pharm. Sci. 2007; 32(4-5): 296-307. https://doi.org/10.1016/j.ejps.2007.08.006
[41] Patel S, Koradia H, Parikh R. Design and development of intranasal in situ gelling system of Midazolam hydrochloride using 32 full factorial design. J. Drug Deliv. Sci. Technol. 2015; 30: 154-62. https://doi.org/10.1016/j.jddst.2015.10.010
[42] Alipour S, Azari H, Ahmadi F. In situ thermosensitive gel of levodopa: Potential formulation for nose to brain delivery in Parkinson disease. Trends Pharm. Sci. 2020; 6(2): 97-104. https://doi.org/10.30476/tips.2020.86526.1052
[43] Antonino RSCMQ, Nascimento TL, de Oliveira Junior ER, Souza LG, Batista AC, Lima EM. Thermoreversible mucoadhesive polymer-drug dispersion for sustained local delivery of budesonide to treat inflammatory disorders of the GI tract. J. Contr. Release. 2019; 303: 12-23. https://doi.org/10.1016/j.jconrel.2019.04.011
[44] Shah V, Sharma M, Pandya R, Parikh RK, Bharatiya B, Shukla A, Tsai HC. Quality by Design approach for an in situ gelling microemulsion of Lorazepam via intranasal route. Mater. Sci. Eng. C. 2017; 75: 1231-41. https://doi.org/10.1016/j.msec.2017.03.002
[45] Jagdale S, Shewale N, Kuchekar BS. Optimization of thermoreversible in situ nasal gel of timolol maleate. Scientifica. 2016; 2016. https://doi.org/10.1155/2016/6401267
[46] Abdelnabi DM, Abdallah MH, Elghamry HA. Buspirone hydrochloride loaded in situ nanovesicular gel as an anxiolytic nasal drug delivery system: In vitro and animal studies. AAPS PharmSciTech. 2019; 20 :1-4. https://doi.org/10.1208/s12249-018-1211-0
[47] Shelke S, Pathan I, Shinde G, Agrawal G, Damale M, Chouthe R, Panzade P, Kulkarni D. Poloxamer-based in situ nasal gel of naratriptan hydrochloride deformable vesicles for brain targeting. BioNanoSci. 2020; 10: 633-48. https://doi.org/10.1007/s12668-020-00767-5
[48] Nižić L, Ugrina I, Špoljarić D, Saršon V, Kučuk MS, Pepić I, Hafner A. Innovative sprayable in situ gelling fluticasone suspension: Development and optimization of nasal deposition. Int. J. Pharm. 2019; 563: 445-56. https://doi.org/10.1016/j.ijpharm.2019.04.015
[49] Chelladurai S, Mishra M, Mishra B. Design and evaluation of bioadhesive in-situ nasal gel of ketorolac tromethamine. Chem. Pharm. Bull. 2008; 56(11): 1596-9. https://doi.org/10.1248/cpb.56.1596
[50] Mohamed S, Nasr M, Salama A, Refai H. Novel lipid–polymer hybrid nanoparticles incorporated in thermosensitive in situ gel for intranasal delivery of terbutaline sulphate. J. Microencapsul. 2020; 37(8): 577-94. https://doi.org/10.1080/02652048.2020.1826590
[51] Patil RP, Pawara DD, Gudewar CS, Tekade AR. Nanostructured cubosomes in an in situ nasal gel system: an alternative approach for the controlled delivery of donepezil HCl to brain. J. Liposome Res. 2019; 29(3): 264-73. https://doi.org/10.1080/08982104.2018.1552703
[52] Paul A, Fathima KM, Nair SC. Intra nasal in situ gelling system of lamotrigine using ion activated mucoadhesive polymer. Open Med. Chem. J. 2017; 11: 222. https://doi.org/10.2174/1874104501711010222
[53] Cho HJ, Balakrishnan P, Park EK, Song KW, Hong SS, Jang TY, Kim KS, Chung SJ, Shim CK, Kim DD. Poloxamer/cyclodextrin/chitosan-based thermoreversible gel for intranasal delivery of fexofenadine hydrochloride. J. Pharm. Sci. 2011; 100(2): 681-91. https://doi.org/10.1002/jps.22314
[54] Malviya V, Ladhake V, Gajbiye K, Satao J, Tawar M. Design and characterization of phase transition system of zolmitriptan hydrochloride for nasal drug delivery system. Int. J. Pharm. Sci. Nanotechnol. (IJPSN). 2020; 13(3): 4942-51. https://doi.org/10.37285/ijpsn.2020.13.3.8
[55] Sousa J, Alves G, Oliveira P, Fortuna A, Falcão A. Intranasal delivery of ciprofloxacin to rats: A topical approach using a thermoreversible in situ gel. Eur. J. Pharm. Sci. 2017; 97: 30-7. https://doi.org/10.1016/j.ejps.2016.10.033
[56] Cao SL, Ren XW, Zhang QZ, Chen E, Xu F, Chen J, Liu LC, Jiang XG. In situ gel based on gellan gum as new carrier for nasal administration of mometasone furoate. Int. J. Pharm. 2009; 365(1-2): 109-15. https://doi.org/10.1016/j.ijpharm.2008.08.042
[57] Salatin S, Alami-Milani M, Daneshgar R, Jelvehgari M. Box–Behnken experimental design for preparation and optimization of the intranasal gels of selegiline hydrochloride. Drug Dev. Ind. Pharm. 2018; 44(10): 1613-21. https://doi.org/10.1080/03639045.2018.1483387
[58] Elkarray SM, Farid RM, Abd-Alhaseeb MM, Omran GA, Habib DA. Intranasal repaglinide-solid lipid nanoparticles integrated in situ gel outperform conventional oral route in hypoglycemic activity. J. Drug Deliv. Sci. Technol. 2022; 68: 103086. https://doi.org/10.1016/j.jddst.2021.103086
[59] Wu C, Qi H, Chen W, Huang C, Su C, Li W, Hou S. Preparation and evaluation of a Carbopol®/HPMC-based in situ gelling ophthalmic system for puerarin. Yakugaku Zasshi. 2007; 127(1): 183-91. https://doi.org/10.1248/yakushi.127.183
[60] Ranch KM, Maulvi FA, Naik MJ, Koli AR, Parikh RK, Shah DO. Optimization of a novel in situ gel for sustained ocular drug delivery using Box-Behnken design: In vitro, ex vivo, in vivo and human studies. Int. J. Pharm. 2019; 554: 264-75. https://doi.org/10.1016/j.ijpharm.2018.11.016
[61] Alsaidan OA, Zafar A, Yasir M, Alzarea SI, Alqinyah M, Khalid M. Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study. Gels. 2022; 8(11): 687. https://doi.org/10.3390/gels8110687
[62] Tuğcu-Demiröz F. Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties. Marmara Pharm. J. 2017; 21(4): 762-70. https://doi.org/10.12991/mpj.2017.3
[63] Kurakula M, Naveen NR. In situ gel loaded with chitosan-coated simvastatin nanoparticles: Promising delivery for effective anti-proliferative activity against tongue carcinoma. Mar. Drugs. 2020; 18(4): 201. https://doi.org/10.3390/md18040201
[64] Gholizadeh H, Messerotti E, Pozzoli M, Cheng S, Traini D, Young P, Kourmatzis A, Caramella C, Ong HX. Application of a thermosensitive in situ gel of chitosan-based nasal spray loaded with tranexamic acid for localised treatment of nasal wounds. AAPS PharmSciTech. 2019; 20: 1-2. https://doi.org/10.1208/s12249-019-1517-6
[65] Kolawole OM, Lau WM, Khutoryanskiy VV. Chitosan/β-glycerophosphate in situ gelling mucoadhesive systems for intravesical delivery of mitomycin-C. Int. J. Pharm.: X. 2019; 1: 100007. https://doi.org/10.1016/j.ijpx.2019.100007
[66] Miyazaki T, Iwanaga A, Shirosaki Y, Kawashita M. In situ synthesis of magnetic iron oxide nanoparticles in chitosan hydrogels as a reaction field: Effect of cross-linking density. Colloids Surf. B Biointerfaces. 2019; 179: 334-9. https://doi.org/10.1016/j.colsurfb.2019.04.004
[67] Jelkmann M, Leichner C, Zaichik S, Laffleur F, Bernkop-Schnürch A. A gellan gum derivative as in situ gelling cationic polymer for nasal drug delivery. Int. J. Biol. Macromol. 2020; 158: 1037-46. https://doi.org/10.1016/j.ijbiomac.2020.04.114
[68] Agibayeva LE, Kaldybekov DB, Porfiryeva NN, Garipova VR, Mangazbayeva RA, Moustafine RI, Semina II, Mun GA, Kudaibergenov SE, Khutoryanskiy VV. Gellan gum and its methacrylated derivatives as in situ gelling mucoadhesive formulations of pilocarpine: In vitro and in vivo studies. Int. J. Pharm. 2020; 577: 119093. https://doi.org/10.1016/j.ijpharm.2020.119093
[69] Huang G, Xie J, Shuai S, Wei S, Chen Y, Guan Z, Zheng Q, Yue P, Wang C. Nose-to-brain delivery of drug nanocrystals by using Ca2+ responsive deacetylated gellan gum based in situ-nanogel. Int. J. Pharm. 2021; 594: 120182. https://doi.org/10.1016/j.ijpharm.2020.120182
[70] Radivojša M, Grabnar I, Grabnar PA. Thermoreversible in situ gelling poloxamer-based systems with chitosan nanocomplexes for prolonged subcutaneous delivery of heparin: Design and in vitro evaluation. Eur. J. Pharm. Sci. 2013; 50(1): 93-101. https://doi.org/10.1016/j.ejps.2013.03.002
[71] Soliman KA, Ullah K, Shah A, Jones DS, Singh TRR. Poloxamer-based in situ gelling thermoresponsive systems for ocular drug delivery applications. Drug Discov. Today. 2019; 24(8): 1575-86. https://doi.org/10.1016/j.drudis.2019.05.036
[72] Abdeltawab H, Svirskis D, Sharma M. Formulation strategies to modulate drug release from poloxamer based in situ gelling systems. Expert Opin. Drug Deliv. 2020; 17(4): 495-509. https://doi.org/10.1080/17425247.2020.1731469
[73] Giuliano E, Paolino D, Cristiano MC, Fresta M, Cosco D. Rutin-loaded poloxamer 407-based hydrogels for in situ administration: stability profiles and rheological properties. Nanomaterials. 2020; 10(6): 1069. https://doi.org/10.3390/nano10061069
[74] Niyompanich J, Chuysinuan P, Pavasant P, Supaphol P. Development of thermoresponsive poloxamer in situ gel loaded with gentamicin sulfate for cavity wounds. J. Polym. Res. 2021; 28: 1-3. https://doi.org/10.1007/s10965-020-02352-6
[75] Shelke S, Pathan I, Shinde G, Agrawal G, Damale M, Chouthe R, Panzade P, Kulkarni D. Poloxamer-based in situ nasal gel of naratriptan hydrochloride deformable vesicles for brain targeting. BioNanoSci.. 2020; 10: 633-48. https://doi.org/10.1007/s12668-020-00767-5
[76] Xia Y, Li L, Huang X, Wang Z, Zhang H, Gao J, Du Y, Chen W, Zheng A. Performance and toxicity of different absorption enhancers used in the preparation of Poloxamer thermosensitive in situ gels for ketamine nasal administration. Drug Dev. Ind. Pharm. 2020; 46(5): 697-705. https://doi.org/10.1080/03639045.2020.1750625
[77] Ponnamma D, Ninan N, Thomas S. Carbon nanotube tube filled polymer nanocomposites and their applications in tissue engineering. InApplications of Nanomaterials 2018; 391-414. Woodhead Publishing. https://doi.org/10.1016/B978-0-08-101971-9.00014-4
[78] Shipp L, Liu F, Kerai-Varsani L, Okwuosa TC. Buccal films: A review of therapeutic opportunities, formulations & relevant evaluation approaches. J. Contr. Release. 2022; 352: 1071-92. https://doi.org/10.1016/j.jconrel.2022.10.058
[79] Kopač T, Ručigaj A, Krajnc M. Effect of polymer-polymer interactions on the flow behavior of some polysaccharide-based hydrogel blends. Carbohydr. Polym. 2022; 287: 119352. https://doi.org/10.1016/j.carbpol.2022.119352
[80] Amasya G, Inal O, Sengel-Turk CT. SLN enriched hydrogels for dermal application: Full factorial design study to estimate the relationship between composition and mechanical properties. Chem. Phys. Lipids. 2020; 228: 104889. https://doi.org/10.1016/j.chemphyslip.2020.104889
[81] Altuntaş E, Yener G. Formulation and evaluation of thermoreversible in situ nasal gels containing mometasone furoate for allergic rhinitis. AAPS PharmSciTech. 2017; 18(7): 2673-82. https://doi.org/10.1208/s12249-017-0747-8
[82] Cevher E, Sensoy D, Taha MAM, Araman A. Effect of thiolated polymers to textural and mucoadhesive properties of vaginal gel formulations prepared with polycarbophil and chitosan. AAPS Pharmscitech. 2008; 9(3): 953-65. https://doi.org/10.1208%2Fs12249-008-9132-y
[83] Ravi PR, Aditya N, Patil S, Cherian L. Nasal in situ gels for delivery of rasagiline mesylate: Improvement in bioavailability and brain localization. Drug Deliv. 2015; 22(7): 903-10. https://doi.org/10.3109/10717544.2014.900150
[84] Aref AA, Refaat A, El Meshad AN, El-Dahmy RM. Chitosan-coated mixed polymeric micelles incorporated in thermosensitive in situ gel for brain targeting of piperine via intranasal route. Int. J. Pharm. 2020; 590: 119915. https://doi.org/10.1016/j.ijpharm.2020.119915
[85] Shaikh U, Kumbhar M, Jagdale S. A review on nasal drug delivery system. Int. J. Pharm. Sci. Rev. Res. 2020; 60(1): 17-24. https://doi.org/10.5530/ijper.54.3.124
[86] Asasutjarit R, Sorrachatanon P, Sukma M, Ritthidej GC. Physicochemical properties and stability of ascorbyl palmitate-loaded nanoparticles in poloxamer-based gels for vaginal administration. AAPS PharmSciTech. 2012; 13: 1186-98. https://doi.org/10.1208/s12249-012-9843-7
[87] Saeed AO, Abdulrasool AA, Abdulameer SA. Development and in-vitro evaluation of thermoreversible mucoadhesive in situ nasal gel formulations of pseudoephedrine hydrochloride. Int. J. Appl. Pharm. 2019; 11(5): 95-102. https://doi.org/10.22159/ijap.2019.v11s5.33540
[88] Saindane NG, Vavia PR. Glucose sensitive dual responsive in situ gel for enhanced ocular retention. Int. J. Pharm. 2021; 596: 120222. https://doi.org/10.1016/j.ijpharm.2021.120222
[89] Almeida H, Amaral MH, Lobão P, Lobo JM. In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug Discov. Today. 2014; 19(4): 400-12. https://doi.org/10.1016/j.drudis.2013.10.002
[90] Chavda HV, Patel MS, Anand IS. Biodegradable in situ gel for subcutaneous administration of simvastatin for prolonged drug delivery. J. Drug Deliv. Sci. Technol. 2020; 59: 101911. https://doi.org/10.1016/j.jddst.2020.101911
[91] He W, Lu Y, Qi J, Chen L, Yin L, Wu W. Bioavailability improvement of an antiepileptic drug via oral administration of nanocrystals prepared by a wet milling method. Drug Deliv. 2011; 18(3): 179-87. https://doi.org/10.3109/10717544.2010.532506
[92] Upadhyay P, Gautam A, Singh D. Formulation and characterization of in-situ nasal gel of lamotrigine for the treatment of epilepsy. Int. J. Curr. Pharm. Res. 2018; 10(1): 24-9. https://doi.org/10.22159/ijcpr.2018.v10i1.22704
[93] Agrawal M, Saraf S, Saraf S, Dubey SK, Puri A, Kurundkar SB, Alexander A. Stimuli-responsive in situ gelling system for nose-to-brain drug delivery. J. Control. Release. 2020; 327: 235-65. https://doi.org/10.1016/j.jconrel.2020.08.024
[94] Song Y, Wang P, Wang X, Wang D, Guo C, Kang W. Synthesis and evaluation of a novel chitosan-based thermosensitive hydrogel for the sustained and efficient delivery of donepezil. Carbohydr. Polym. 2021; 251: 117108. https://doi.org/10.1016/j.carbpol.2020.117108
[95] Singh RM, Kumar A, Pathak K. Mucoadhesive in situ nasal gel of loratadine: Design, development, optimization and evaluation. Int. J. Appl. Pharm. 2011; 3(2): 12-7.
[96] Gavini E, Hegge AB, Rassu G, Sanna V, Testa C, Pirisino G, Karlsen J, Giunchedi P. Nasal administration of carbamazepine using chitosan microspheres: In vitro/in vivo studies. Int. J. Pharm. 2006; 307(1): 9-15. https://doi.org/10.1016/j.ijpharm.2005.10.003
[97] Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RF. A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur. J. Pharm. Biopharm. 2010; 75(2): 186-93. https://doi.org/10.1016/j.ejpb.2010.02.017

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Yavuz Selim Çelik This is me
0000-0001-9601-4615
Türkiye

Büşra Örenli This is me
0000-0001-7013-1872
Türkiye

Mazen Al-mohaya This is me
0000-0003-4176-0308
Türkiye

Burcu Mesut ^* This is me
Türkiye

Yıldız Özsoy This is me
0000-0002-9110-3704
Türkiye

Publication Date

June 28, 2025

Submission Date

April 24, 2023

Acceptance Date

April 27, 2023

Published in Issue

Year 2023 Volume: 27 Number: 5

IZ

https://izlik.org/JA23AY48TZ

Cite

RIS / Bibtex

APA

Çelik, Y. S., Örenli, B., Al-mohaya, M., Mesut, B., & Özsoy, Y. (2025). Nasal in situ gels as a drug delivery system: An overview of literature and clinical studies. Journal of Research in Pharmacy, 27(5), 1875-1888. https://izlik.org/JA23AY48TZ

AMA

1.Çelik YS, Örenli B, Al-mohaya M, Mesut B, Özsoy Y. Nasal in situ gels as a drug delivery system: An overview of literature and clinical studies. J. Res. Pharm. 2025;27(5):1875-1888. https://izlik.org/JA23AY48TZ

Chicago

Çelik, Yavuz Selim, Büşra Örenli, Mazen Al-mohaya, Burcu Mesut, and Yıldız Özsoy. 2025. “Nasal in Situ Gels As a Drug Delivery System: An Overview of Literature and Clinical Studies”. Journal of Research in Pharmacy 27 (5): 1875-88. https://izlik.org/JA23AY48TZ.

EndNote

Çelik YS, Örenli B, Al-mohaya M, Mesut B, Özsoy Y (July 1, 2025) Nasal in situ gels as a drug delivery system: An overview of literature and clinical studies. Journal of Research in Pharmacy 27 5 1875–1888.

IEEE

[1]Y. S. Çelik, B. Örenli, M. Al-mohaya, B. Mesut, and Y. Özsoy, “Nasal in situ gels as a drug delivery system: An overview of literature and clinical studies”, J. Res. Pharm., vol. 27, no. 5, pp. 1875–1888, July 2025, [Online]. Available: https://izlik.org/JA23AY48TZ

ISNAD

Çelik, Yavuz Selim - Örenli, Büşra - Al-mohaya, Mazen - Mesut, Burcu - Özsoy, Yıldız. “Nasal in Situ Gels As a Drug Delivery System: An Overview of Literature and Clinical Studies”. Journal of Research in Pharmacy 27/5 (July 1, 2025): 1875-1888. https://izlik.org/JA23AY48TZ.

JAMA

1.Çelik YS, Örenli B, Al-mohaya M, Mesut B, Özsoy Y. Nasal in situ gels as a drug delivery system: An overview of literature and clinical studies. J. Res. Pharm. 2025;27:1875–1888.

MLA

Çelik, Yavuz Selim, et al. “Nasal in Situ Gels As a Drug Delivery System: An Overview of Literature and Clinical Studies”. Journal of Research in Pharmacy, vol. 27, no. 5, July 2025, pp. 1875-88, https://izlik.org/JA23AY48TZ.

Vancouver

1.Yavuz Selim Çelik, Büşra Örenli, Mazen Al-mohaya, Burcu Mesut, Yıldız Özsoy. Nasal in situ gels as a drug delivery system: An overview of literature and clinical studies. J. Res. Pharm. [Internet]. 2025 Jul. 1;27(5):1875-88. Available from: https://izlik.org/JA23AY48TZ