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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

In-situ Gels for Brain Delivery: Breaching the Barriers

Author(s): Gul Naz Fatima, Priyanka Maurya, Nishtha and Shailendra K. Saraf*

Volume 29, Issue 40, 2023

Published on: 10 August, 2023

Page: [3240 - 3253] Pages: 14

DOI: 10.2174/1381612829666230803114513

Price: $65

Abstract

The blood-brain barrier (BBB) regulates blood and chemical exchange in the central nervous system. It is made up of brain parenchyma capillary endothelial cells. It separates the interstitial cerebrospinal fluid from the circulation and limits brain drug entry. Peptides, antibodies, and even tiny hydrophilic biomolecules cannot flow across the BBB due to their semi-permeability. It protects the brain from poisons, chemicals, and pathogens, and blood cells penetrate brain tissue. BBB-facilitated carrier molecules allow selective permeability of nutrients such as D-glucose, L-lactic acid, L-phenylalanine, L-arginine, and hormones, especially steroid hormones. Brain barriers prevent drug molecules from entering, making medication delivery difficult. Drugs can reach specific brain regions through the nasal cavity, making it a preferred route. The in-situ gels are mucoadhesive, which extends their stay in the nasal cavity, allows them to penetrate deep and makes them a dependable way of transporting numerous medications, including peptides and proteins, straight into the central nervous system. This approach holds great potential for neurological therapy as they deliver drugs directly to the central nervous system, with less interference and better drug release control. The brain affects daily life by processing sensory stimuli, controlling movement and behaviour, and sustaining mental, emotional, and cognitive functioning. Unlike systemic routes, the nasal mucosa is extensively vascularized and directly contacts olfactory sensory neurons. Compared to the systemic circulation, this improves brain bioavailability of medications. Drugs can be delivered to the brain using in-situ gel formulations safely and efficiently, with a greater therapeutic impact than with traditional techniques.

« Previous Next »
[1]
Upadhyay RK. Drug delivery systems, CNS protection, and the blood brain barrier. BioMed Res Int 2014; 2014: 1-37.
[http://dx.doi.org/10.1155/2014/869269] [PMID: 25136634]
[2]
Wang Y, Pan Y, Li H. What is brain health and why is it important? BMJ 2020; 371: m3683.
[http://dx.doi.org/10.1136/bmj.m3683] [PMID: 33037002]
[3]
Cieza A, Anczewska M, Ayuso-Mateos JL, et al. Understanding the impact of brain disorders: Towards a ‘horizontal epidemiology’ of psychosocial difficulties and their determinants. PLoS One 2015; 10(9): e0136271.
[http://dx.doi.org/10.1371/journal.pone.0136271] [PMID: 26352911]
[4]
Mulvihill JJE, Cunnane EM, Ross AM, Duskey JT, Tosi G, Grabrucker AM. Drug delivery across the blood-brain barrier: Recent advances in the use of nanocarriers. Nanomedicine (Lond) 2020; 15(2): 205-14.
[http://dx.doi.org/10.2217/nnm-2019-0367] [PMID: 31916480]
[5]
Paulson O. Blood-brain barrier, brain metabolism and cerebral blood flow. Eur Neuropsychopharmacol 2002; 12(6): 495-501.
[http://dx.doi.org/10.1016/S0924-977X(02)00098-6] [PMID: 12468012]
[6]
Zhang S, Gan L, Cao F, et al. The barrier and interface mechanisms of the brain barrier, and brain drug delivery. Brain Res Bull 2022; 190: 69-83.
[http://dx.doi.org/10.1016/j.brainresbull.2022.09.017] [PMID: 36162603]
[7]
Bellettato CM, Scarpa M. Possible strategies to cross the blood-brain barrier. Ital J Pediatr 2018; 44(S2) (Suppl. 2): 131.
[http://dx.doi.org/10.1186/s13052-018-0563-0] [PMID: 30442184]
[8]
Bell RD, Ehlers MD. Breaching the blood-brain barrier for drug delivery. Neuron 2014; 81(1): 1-3.
[http://dx.doi.org/10.1016/j.neuron.2013.12.023] [PMID: 24411725]
[9]
Sanchez-Covarrubias L, Slosky L, Thompson B, Davis T, Ronaldson P. Transporters at CNS barrier sites: Obstacles or opportunities for drug delivery? Curr Pharm Des 2014; 20(10): 1422-49.
[http://dx.doi.org/10.2174/13816128113199990463] [PMID: 23789948]
[10]
Pardridge WM. Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab 2012; 32(11): 1959-72.
[http://dx.doi.org/10.1038/jcbfm.2012.126] [PMID: 22929442]
[11]
Hong SS, Oh KT, Choi HG, Lim SJ. Liposomal formulations for nose-to-brain delivery: Recent advances and future perspectives. Pharmaceutics 2019; 11(10): 540.
[http://dx.doi.org/10.3390/pharmaceutics11100540] [PMID: 31627301]
[12]
Pardridge WM, Mietus LJ. Transport of steroid hormones through the rat blood-brain barrier. Primary role of albumin-bound hormone. J Clin Invest 1979; 64(1): 145-54.
[http://dx.doi.org/10.1172/JCI109433] [PMID: 447850]
[13]
Ghosh C, Puvenna V, Gonzalez-Martinez J, Janigro D, Marchi N. Blood-brain barrier P450 enzymes and multidrug transporters in drug resistance: A synergistic role in neurological diseases. Curr Drug Metab 2011; 12(8): 742-9.
[http://dx.doi.org/10.2174/138920011798357051] [PMID: 21568937]
[14]
Teleanu RI, Preda MD, Niculescu AG, et al. Current strategies to enhance delivery of drugs across the blood-brain barrier. Pharmaceutics 2022; 14(5): 987.
[http://dx.doi.org/10.3390/pharmaceutics14050987] [PMID: 35631573]
[15]
Solár P, Zamani A, Kubíčková L, Dubový P, Joukal M. Choroid plexus and the blood-cerebrospinal fluid barrier in disease. Fluids Barriers CNS 2020; 17(1): 35.
[http://dx.doi.org/10.1186/s12987-020-00196-2] [PMID: 32375819]
[16]
Tumani H, Huss A, Bachhuber F. The cerebrospinal fluid and barriers - anatomic and physiologic considerations. Handb Clin Neurol 2018; 146: 21-32.
[http://dx.doi.org/10.1016/B978-0-12-804279-3.00002-2] [PMID: 29110772]
[17]
Pandit R, Chen L, Götz J. The blood-brain barrier: Physiology and strategies for drug delivery. Adv Drug Deliv Rev 2020; 165-166: 1-14.
[http://dx.doi.org/10.1016/j.addr.2019.11.009] [PMID: 31790711]
[18]
Chen Y, Dalwadi G, Benson H. Drug delivery across the blood- brain barrier. Curr Drug Deliv 2004; 1(4): 361-76.
[http://dx.doi.org/10.2174/1567201043334542] [PMID: 16305398]
[19]
Wang Q, Zuo Z. Impact of transporters and enzymes from blood- cerebrospinal fluid barrier and brain parenchyma on CNS drug uptake. Expert Opin Drug Metab Toxicol 2018; 14(9): 961-72.
[http://dx.doi.org/10.1080/17425255.2018.1513493] [PMID: 30118608]
[20]
Sharma G, Lakkadwala S, Modgil A, Singh J. The role of cell-penetrating peptide and transferrin on enhanced delivery of drug to brain. Int J Mol Sci 2016; 17(6): 806.
[http://dx.doi.org/10.3390/ijms17060806] [PMID: 27231900]
[21]
Liu J, Li M, Huang Y, et al. A nanogel with effective blood-brain barrier penetration ability through passive and active dual-targeting function. J Nanomater 2021; 2021
[http://dx.doi.org/10.1155/2021/6623031]
[22]
Zhang TT, Li W, Meng G, Wang P, Liao W. Strategies for transporting nanoparticles across the blood-brain barrier. Biomater Sci 2016; 4(2): 219-29.
[http://dx.doi.org/10.1039/C5BM00383K] [PMID: 26646694]
[23]
Bahadur S, Jha MK. Emerging nanoformulations for drug targeting to brain through intranasal delivery: A comprehensive review. J Drug Deliv Sci Technol 2022; 78: 103932.
[http://dx.doi.org/10.1016/j.jddst.2022.103932]
[24]
Lin T, Liu E, He H, et al. Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides. Acta Pharm Sin B 2016; 6(4): 352-8.
[http://dx.doi.org/10.1016/j.apsb.2016.04.001] [PMID: 27471676]
[25]
Zou LL, Ma JL, Wang T, Yang TB, Liu CB. Cell-penetrating Peptide-mediated therapeutic molecule delivery into the central nervous system. Curr Neuropharmacol 2013; 11(2): 197-208.
[http://dx.doi.org/10.2174/1570159X11311020006] [PMID: 23997754]
[26]
Liu Y, Zhao Z, Li M. Overcoming the cellular barriers and beyond: Recent progress on cell penetrating peptide modified nanomedicine in combating physiological and pathological barriers. Asian J Pharm Sci 2022; 17(4): 523-43.
[http://dx.doi.org/10.1016/j.ajps.2022.05.002] [PMID: 36105313]
[27]
He H, Ye J, Liu E, Liang Q, Liu Q, Yang VC. Low molecular weight protamine (LMWP): A nontoxic protamine substitute and an effective cell-penetrating peptide. J Control Release 2014; 193: 63-73.
[http://dx.doi.org/10.1016/j.jconrel.2014.05.056] [PMID: 24943246]
[28]
Lim S, Koo JH, Choi JM. Use of cell-penetrating peptides in dendritic cell-based vaccination. Immune Netw 2016; 16(1): 33-43.
[http://dx.doi.org/10.4110/in.2016.16.1.33] [PMID: 26937230]
[29]
Wang Z, Chen Y, Liu E, Gong J, Shin M, Huang Y. CPP-mediated protein delivery in a noncovalent form: Proof-of-concept for percutaneous and intranasal delivery. Protein Pept Lett 2014; 21(11): 1129-36.
[http://dx.doi.org/10.2174/0929866521666140807121903] [PMID: 25106905]
[30]
Roberts HC, Roberts TPL, Bollen AW, Ley S, Brasch RC, Dillon WP. Correlation of microvascular permeability derived from dynamic contrast-enhanced MR imaging with histologic grade and tumor labeling index: A study in human brain tumors. Acad Radiol 2001; 8(5): 384-91.
[http://dx.doi.org/10.1016/S1076-6332(03)80545-7] [PMID: 11345268]
[31]
Papadopoulos MC, Saadoun S, Davies DC, Bell BA. Emerging molecular mechanisms of brain tumour oedema. Br J Neurosurg 2001; 15(2): 101-8.
[http://dx.doi.org/10.1080/02688690120036775] [PMID: 11360371]
[32]
Ferraris C, Cavalli R, Panciani PP, Battaglia L. Overcoming the blood-brain barrier: Successes and challenges in developing nanoparticle-mediated drug delivery systems for the treatment of brain tumours. Int J Nanomedicine 2020; 15: 2999-3022.
[http://dx.doi.org/10.2147/IJN.S231479] [PMID: 32431498]
[33]
Tortorella S, Karagiannis TC. Transferrin receptor-mediated endocytosis: A useful target for cancer therapy. J Membr Biol 2014; 247(4): 291-307.
[http://dx.doi.org/10.1007/s00232-014-9637-0] [PMID: 24573305]
[34]
Tashima T. Smart strategies for therapeutic agent delivery into brain across the blood-brain barrier using receptor-mediated transcytosis. Chem Pharm Bull 2020; 68(4): 316-25.
[http://dx.doi.org/10.1248/cpb.c19-00854] [PMID: 32238649]
[35]
Lajoie JM, Shusta EV. Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier. Annu Rev Pharmacol Toxicol 2015; 55(1): 613-31.
[http://dx.doi.org/10.1146/annurev-pharmtox-010814-124852] [PMID: 25340933]
[36]
Fang F, Zou D, Wang W, et al. Non-invasive approaches for drug delivery to the brain based on the receptor mediated transport. Mater Sci Eng C 2017; 76: 1316-27.
[http://dx.doi.org/10.1016/j.msec.2017.02.056] [PMID: 28482500]
[37]
Rip J, Schenk GJ, de Boer AG. Differential receptor-mediated drug targeting to the diseased brain. Expert Opin Drug Deliv 2009; 6(3): 227-37.
[http://dx.doi.org/10.1517/17425240902806383] [PMID: 19327042]
[38]
Sandbhor P, Goda J, Mohanty B, et al. Targeted nano-delivery of chemotherapy via intranasal route suppresses in vivo glioblastoma growth and prolongs survival in the intracranial mouse model. Drug Deliv Transl Res 2023; 13(2): 608-26.
[http://dx.doi.org/10.1007/s13346-022-01220-8] [PMID: 36245060]
[39]
Islam SU, Shehzad A, Ahmed MB, Lee YS. Intranasal delivery of nanoformulations: A potential way of treatment for neurological disorders. Molecules 2020; 25(8): 1929.
[http://dx.doi.org/10.3390/molecules25081929] [PMID: 32326318]
[40]
Pardeshi CV, Belgamwar VS. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: An excellent platform for brain targeting. Expert Opin Drug Deliv 2013; 10(7): 957-72.
[http://dx.doi.org/10.1517/17425247.2013.790887] [PMID: 23586809]
[41]
Patel Z, Patel B, Patel S, Pardeshi C. Nose to brain targeted drug delivery bypassing the blood-brain barrier: An overview. Drug Invent Today 2012; 2012: 4.
[42]
Danielyan L, Schäfer R, von Ameln-Mayerhofer A, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol 2009; 88(6): 315-24.
[http://dx.doi.org/10.1016/j.ejcb.2009.02.001] [PMID: 19324456]
[43]
Aly AEE, Waszczak BL. Intranasal gene delivery for treating Parkinson’s disease: Overcoming the blood-brain barrier. Expert Opin Drug Deliv 2015; 12(12): 1923-41.
[http://dx.doi.org/10.1517/17425247.2015.1069815] [PMID: 26289676]
[44]
Erdő F, Bors LA, Farkas D, Bajza Á, Gizurarson S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res Bull 2018; 143: 155-70.
[http://dx.doi.org/10.1016/j.brainresbull.2018.10.009] [PMID: 30449731]
[45]
Costantino HR, Illum L, Brandt G, Johnson PH, Quay SC. Intranasal delivery: Physicochemical and therapeutic aspects. Int J Pharm 2007; 337(1-2): 1-24.
[http://dx.doi.org/10.1016/j.ijpharm.2007.03.025] [PMID: 17475423]
[46]
Lee D, Minko T. Nanotherapeutics for nose-to-brain drug delivery: An approach to bypass the blood brain barrier. Pharmaceutics 2021; 13(12): 2049.
[http://dx.doi.org/10.3390/pharmaceutics13122049] [PMID: 34959331]
[47]
Adnet T, Groo AC, Picard C, et al. Pharmacotechnical development of a nasal drug delivery composite nanosystem intended for Alzheimer’s disease treatment. Pharmaceutics 2020; 12(3): 251.
[http://dx.doi.org/10.3390/pharmaceutics12030251] [PMID: 32168767]
[48]
Costa CP, Moreira JN, Sousa Lobo JM, Silva AC. Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of in vivo studies. Acta Pharm Sin B 2021; 11(4): 925-40.
[http://dx.doi.org/10.1016/j.apsb.2021.02.012] [PMID: 33996407]
[49]
Ambavkar A, Desai N. Development and evaluation of nanoparticulate based in-situ gelling system for nasal drug delivery of an anti-epileptic drug. European J Pharmaceut Sci 2022; 179: 106294.
[http://dx.doi.org/10.53879/id.54.09.10774]
[50]
Patel HP, Gandhi PA, Chaudhari PS, et al. Clozapine loaded nanostructured lipid carriers engineered for brain targeting via nose-to-brain delivery: Optimization and in vivo pharmacokinetic studies. J Drug Deliv Sci Technol 2021; 64: 102533.
[http://dx.doi.org/10.1016/j.jddst.2021.102533]
[51]
Chatterjee B, Gorain B, Mohananaidu K, Sengupta P, Mandal UK, Choudhury H. Targeted drug delivery to the brain via intranasal nanoemulsion: Available proof of concept and existing challenges. Int J Pharm 2019; 565: 258-68.
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.032] [PMID: 31095983]
[52]
Bahadur S, Pardhi DM, Rautio J, Rosenholm JM, Pathak K. Intranasal nanoemulsions for direct nose-to-brain delivery of actives for cns disorders. Pharmaceutics 2020; 12(12): 1230.
[http://dx.doi.org/10.3390/pharmaceutics12121230] [PMID: 33352959]
[53]
Pacheco C, Sousa F, Sarmento B. Chitosan-based nanomedicine for brain delivery: Where are we heading? React Funct Polym 2020; 146: 104430.
[http://dx.doi.org/10.1016/j.reactfunctpolym.2019.104430]
[54]
Ansari R, Sadati SM, Mozafari N, Ashrafi H, Azadi A. Carbohydrate polymer-based nanoparticle application in drug delivery for CNS-related disorders. Eur Polym J 2020; 128: 109607.
[http://dx.doi.org/10.1016/j.eurpolymj.2020.109607]
[55]
Kaur S, Manhas P, Swami A, et al. Bioengineered PLGA-chitosan nanoparticles for brain targeted intranasal delivery of antiepileptic TRH analogues. Chem Eng J 2018; 346: 630-9.
[http://dx.doi.org/10.1016/j.cej.2018.03.176]
[56]
Hao R, Sun B, Yang L, Ma C, Li S. RVG29-modified microRNA-loaded nanoparticles improve ischemic brain injury by nasal delivery. Drug Deliv 2020; 27(1): 772-81.
[http://dx.doi.org/10.1080/10717544.2020.1760960] [PMID: 32400219]
[57]
Mignani S, Shi X, Karpus A, Majoral JP. Non-invasive intranasal administration route directly to the brain using dendrimer nanoplatforms: An opportunity to develop new CNS drugs. Eur J Med Chem 2021; 209: 112905.
[http://dx.doi.org/10.1016/j.ejmech.2020.112905] [PMID: 33069435]
[58]
Choudhury H, Pandey M, Mohgan R, et al. Dendrimer-based delivery of macromolecules for the treatment of brain tumor. Biomaterials Advances 2022; 141: 213118.
[http://dx.doi.org/10.1016/j.bioadv.2022.213118] [PMID: 36182834]
[59]
Gauro R, Nandave M, Jain VK, Jain K. Advances in dendrimer- mediated targeted drug delivery to the brain. J Nanopart Res 2021; 23(3): 76.
[http://dx.doi.org/10.1007/s11051-021-05175-8]
[60]
Kaur P, Garg T, Rath G, Goyal AK. In situ nasal gel drug delivery: A novel approach for brain targeting through the mucosal membrane. Artif Cells Nanomed Biotechnol 2016; 44(4): 1167-76.
[PMID: 25749276]
[61]
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.
[http://dx.doi.org/10.3109/10717544.2013.860501] [PMID: 24286183]
[62]
Kaur P, Garg T, Vaidya B, Prakash A, Rath G, Goyal AK. Brain delivery of intranasal in situ gel of nanoparticulated polymeric carriers containing antidepressant drug: Behavioral and biochemical assessment. J Drug Target 2015; 23(3): 275-86.
[http://dx.doi.org/10.3109/1061186X.2014.994097] [PMID: 25539073]
[63]
Aderibigbe B. In situ-based gels for nose to brain delivery for the treatment of neurological diseases. Pharmaceutics 2018; 10(2): 40.
[http://dx.doi.org/10.3390/pharmaceutics10020040] [PMID: 29601486]
[64]
Sabir F, Ain QU, Rahdar A, et al. Functionalized nanoparticles in drug delivery: Strategies to enhance direct nose-to-brain drug delivery via integrated nerve pathways. Synthesis and Applications of Nanoparticles. Singapore: Springer Nature 2022; pp. 455-85.
[65]
Kouchak M. In situ gelling systems for drug delivery. Jundishapur J Nat Pharm Prod 2014; 9(3): e20126.
[http://dx.doi.org/10.17795/jjnpp-20126] [PMID: 25237648]
[66]
Kolawole OM, Cook MT. In situ gelling drug delivery systems for topical drug delivery. Eur J Pharm Biopharm 2023; 184: 36-49.
[http://dx.doi.org/10.1016/j.ejpb.2023.01.007] [PMID: 36642283]
[67]
Madan M, Bajaj A, Lewis S, Udupa N, Baig JA. In situ forming polymeric drug delivery systems. Indian J Pharm Sci 2009; 71(3): 242-51.
[http://dx.doi.org/10.4103/0250-474X.56015] [PMID: 20490289]
[68]
Ganguly S, Dash AK. A novel in situ gel for sustained drug delivery and targeting. Int J Pharm 2004; 276(1-2): 83-92.
[http://dx.doi.org/10.1016/j.ijpharm.2004.02.014] [PMID: 15113617]
[69]
Miyazaki S, Suzuki S, Kawasaki N, Endo K, Takahashi A, Attwood D. In situ gelling xyloglucan formulations for sustained release ocular delivery of pilocarpine hydrochloride. Int J Pharm 2001; 229(1-2): 29-36.
[http://dx.doi.org/10.1016/S0378-5173(01)00825-0] [PMID: 11604255]
[70]
Liu Y, Liu J, Zhang X, Zhang R, Huang Y, Wu C. In situ gelling gelrite/alginate formulations as vehicles for ophthalmic drug delivery. AAPS PharmSciTech 2010; 11(2): 610-20.
[http://dx.doi.org/10.1208/s12249-010-9413-0] [PMID: 20354916]
[71]
Agrawal AK, Das M, Jain S. In situ gel systems as ‘smart’ carriers for sustained ocular drug delivery. Expert Opin Drug Deliv 2012; 9(4): 383-402.
[http://dx.doi.org/10.1517/17425247.2012.665367] [PMID: 22432690]
[72]
Gupta H, Velpandian T, Jain S. Ion- and pH-activated novel in-situ gel system for sustained ocular drug delivery. J Drug Target 2010; 18(7): 499-505.
[http://dx.doi.org/10.3109/10611860903508788] [PMID: 20055752]
[73]
Yadav R, Kanwar IL, Haider T, Pandey V, Gour V, Soni V. In situ gel drug delivery system for periodontitis: An insight review. Future J Pharm Sci 2020; 6(1): 33.
[http://dx.doi.org/10.1186/s43094-020-00053-x]
[74]
Uma Maheshwari TN, Inchara R. In situ gel treatment for oral mucosal lesions: A systematic review. J Int Oral Health 2020; 12(6): 499-503.
[http://dx.doi.org/10.4103/JIOH.JIOH_257_20]
[75]
Xu H, Shi M, liu Y, Jiang J, Ma T. A novel in situ gel formulation of ranitidine for oral sustained delivery. Biomol Ther 2014; 22(2): 161-5.
[http://dx.doi.org/10.4062/biomolther.2013.109] [PMID: 24753823]
[76]
A S, Ahmed MG, Gowda BH J. Preparation and evaluation of in-situ gels containing hydrocortisone for the treatment of aphthous ulcer. J Oral Biol Craniofac Res 2021; 11(2): 269-76.
[http://dx.doi.org/10.1016/j.jobcr.2021.02.001] [PMID: 33717865]
[77]
Zeng N, Seguin J, Destruel PL, et al. Cyanine derivative as a suitable marker for thermosensitive in situ gelling delivery systems: In vitro and in vivo validation of a sustained buccal drug delivery. Int J Pharm 2017; 534(1-2): 128-35.
[http://dx.doi.org/10.1016/j.ijpharm.2017.09.073] [PMID: 28982548]
[78]
Elmowafy E, Cespi M, Bonacucina G, Soliman ME. In situ composite ion-triggered gellan gum gel incorporating amino methacrylate copolymer microparticles: A therapeutic modality for buccal applicability. Pharm Dev Technol 2019; 24(10): 1258-71.
[http://dx.doi.org/10.1080/10837450.2019.1659314] [PMID: 31437077]
[79]
Liu Y, Zhu Y, Wei G, Lu W. Effect of carrageenan on poloxamer-based in situ gel for vaginal use: Improved in vitro and in vivo sustained-release properties. Eur J Pharm Sci 2009; 37(3-4): 306-12.
[http://dx.doi.org/10.1016/j.ejps.2009.02.022] [PMID: 19491020]
[80]
Deshkar SS, Palve VK. Formulation and development of thermosensitive cyclodextrin-based in situ gel of voriconazole for vaginal delivery. J Drug Deliv Sci Technol 2019; 49: 277-85.
[http://dx.doi.org/10.1016/j.jddst.2018.11.023]
[81]
Permana AD, Utomo E, Pratama MR, et al. Bioadhesive-thermosensitive in situ vaginal gel of the gel flake-solid dispersion of itraconazole for enhanced antifungal activity in the treatment of vaginal candidiasis. ACS Appl Mater Interfaces 2021; 13(15): 18128-41.
[http://dx.doi.org/10.1021/acsami.1c03422] [PMID: 33840187]
[82]
Salem HF, Ali AA, Rabea YK, El-Ela FIA, Khallaf RA. Glycerosomal thermosensitive in situ gel of duloxetine HCl as a novel nanoplatform for rectal delivery: In vitro optimization and in vivo appraisal. Drug Deliv Transl Res 2022; 12(12): 3083-103.
[http://dx.doi.org/10.1007/s13346-022-01172-z] [PMID: 35622235]
[83]
Moawad FA, Ali AA, Salem HF. Nanotransfersomes-loaded thermosensitive in situ gel as a rectal delivery system of tizanidine HCl: Preparation, in vitro and in vivo performance. Drug Deliv 2017; 24(1): 252-60.
[http://dx.doi.org/10.1080/10717544.2016.1245369] [PMID: 28156169]
[84]
Huang C, Hu P, Wu Q, et al. Preparation, in vitro and in vivo evaluation of thermosensitive in situ gel loaded with ibuprofen-solid lipid nanoparticles for rectal delivery. Drug Des Devel Ther 2022; 16: 1407-31.
[http://dx.doi.org/10.2147/DDDT.S350886] [PMID: 35586185]
[85]
Berrada M, Serreqi A, Dabbarh F, Owusu A, Gupta A, Lehnert S. A novel non-toxic camptothecin formulation for cancer chemotherapy. Biomaterials 2005; 26(14): 2115-20.
[http://dx.doi.org/10.1016/j.biomaterials.2004.06.013] [PMID: 15576186]
[86]
Kempe S, Mäder K. In situ forming implants - an attractive formulation principle for parenteral depot formulations. J Control Release 2012; 161(2): 668-79.
[http://dx.doi.org/10.1016/j.jconrel.2012.04.016] [PMID: 22543012]
[87]
Packhaeuser CB, Schnieders J, Oster CG, Kissel T. In situ forming parenteral drug delivery systems: An overview. Eur J Pharm Biopharm 2004; 58(2): 445-55.
[http://dx.doi.org/10.1016/j.ejpb.2004.03.003] [PMID: 15296966]
[88]
Polat HK. Sedat Ü. Development of besifloxacin HCL loaded ocular in situ gels; in vitro characterization study. J Fac Pharm Ankara Univ 2023; 47: 4-4.
[89]
Bayanati M, Khosroshahi AG, Alvandi M, Mahboobian MM. Fabrication of a thermosensitive in situ gel nanoemulsion for nose to brain delivery of temozolomide. J Nanomater 2021; 2021: 1-11.
[http://dx.doi.org/10.1155/2021/1546798]
[90]
Chen Y, Liu Y, Xie J, et al. Nose-to-brain delivery by nanosuspensions-based in situ gel for breviscapine. Int J Nanomedicine 2020; 15: 10435-51.
[http://dx.doi.org/10.2147/IJN.S265659] [PMID: 33380794]
[91]
Zaki NM, Awad GA, Mortada ND, Abd ElHady SS. 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.
[http://dx.doi.org/10.1016/j.ejps.2007.08.006] [PMID: 17920822]
[92]
Qian S, Wong YC, Zuo Z. Development, characterization and application of in situ gel systems for intranasal delivery of tacrine. Int J Pharm 2014; 468(1-2): 272-82.
[http://dx.doi.org/10.1016/j.ijpharm.2014.04.015] [PMID: 24709220]
[93]
Sridhar V, Wairkar S, Gaud R, Bajaj A, Meshram P. Brain targeted delivery of mucoadhesive thermosensitive nasal gel of selegiline hydrochloride for treatment of Parkinson’s disease. J Drug Target 2018; 26(2): 150-61.
[http://dx.doi.org/10.1080/1061186X.2017.1350858] [PMID: 28682134]
[94]
Abbas H, Refai H, El Sayed N. Superparamagnetic iron oxide-loaded lipid nanocarriers incorporated in thermosensitive in situ gel for magnetic brain targeting of clonazepam. J Pharm Sci 2018; 107(8): 2119-27.
[http://dx.doi.org/10.1016/j.xphs.2018.04.007] [PMID: 29665379]
[95]
Mayol L, Quaglia F, Borzacchiello A, Ambrosio L, Rotonda M. A novel poloxamers/hyaluronic acid in situ forming hydrogel for drug delivery: Rheological, mucoadhesive and in vitro release properties. Eur J Pharm Biopharm 2008; 70(1): 199-206.
[http://dx.doi.org/10.1016/j.ejpb.2008.04.025] [PMID: 18644705]
[96]
Karatas A, Boluk A, Algan A. Poloxamer/Chitosan in situ gelling system for ocular delivery of ofloxacin. Curr Drug Ther 2015; 9(4): 219-25.
[http://dx.doi.org/10.2174/1574885510999150505171515]
[97]
Mansour M, Mansour S, Mortada ND, Abd ElHady SS. Ocular poloxamer-based ciprofloxacin hydrochloride in situ forming gels. Drug Dev Ind Pharm 2008; 34(7): 744-52.
[http://dx.doi.org/10.1080/03639040801926030] [PMID: 18612913]
[98]
Cho K, Chung TW, Kim BC, et al. Release of ciprofloxacin from poloxamer-graft-hyaluronic acid hydrogels in vitro. Int J Pharm 2003; 260(1): 83-91.
[http://dx.doi.org/10.1016/S0378-5173(03)00259-X] [PMID: 12818813]
[99]
Lin HR, Sung KC, Vong WJ. In situ gelling of alginate/pluronic solutions for ophthalmic delivery of pilocarpine. Biomacromolecules 2004; 5(6): 2358-65.
[http://dx.doi.org/10.1021/bm0496965] [PMID: 15530052]
[100]
Yu S, Zhang X, Tan G, et al. A novel pH-induced thermosensitive hydrogel composed of carboxymethyl chitosan and poloxamer cross-linked by glutaraldehyde for ophthalmic drug delivery. Carbohydr Polym 2017; 155: 208-17.
[http://dx.doi.org/10.1016/j.carbpol.2016.08.073] [PMID: 27702506]
[101]
Pachis K, Blazaki S, Tzatzarakis M, et al. Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation. Eur J Pharm Sci 2017; 109: 324-33.
[http://dx.doi.org/10.1016/j.ejps.2017.08.028] [PMID: 28843864]
[102]
Sherif AY, Mahrous GM, Alanazi FK. Novel in-situ gel for intravesical administration of ketorolac. Saudi Pharm J 2018; 26(6): 845-51.
[http://dx.doi.org/10.1016/j.jsps.2018.03.014] [PMID: 30202226]
[103]
Yang G, Wang Q, Gao Y, Yang C, Hu L. Combination of coating and injectable hydrogel depot to improve the sustained delivery of insulin. J Drug Deliv Sci Technol 2018; 45: 415-21.
[http://dx.doi.org/10.1016/j.jddst.2018.03.028]
[104]
Jung Y, Park W, Park H, Lee DK, Na K. Thermo-sensitive injectable hydrogel based on the physical mixing of hyaluronic acid and Pluronic F-127 for sustained NSAID delivery. Carbohydr Polym 2017; 156: 403-8.
[http://dx.doi.org/10.1016/j.carbpol.2016.08.068] [PMID: 27842839]
[105]
Russo E, Gaglianone N, Baldassari S, et al. Chitosan-clodronate nanoparticles loaded in poloxamer gel for intra-articular administration. Colloids Surf B Biointerfaces 2016; 143: 88-96.
[http://dx.doi.org/10.1016/j.colsurfb.2016.03.028] [PMID: 26998870]
[106]
Küçüktürkmen B, Öz UC, Bozkir A. In situ hydrogel formulation for intra-articular application of diclofenac sodium-loaded polymeric nanoparticles. J Pharm Sci 207; 14(1): 56-64.
[107]
Yuan Y, Cui Y, Zhang L, et al. Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesulide. Int J Pharm 2012; 430(1-2): 114-9.
[http://dx.doi.org/10.1016/j.ijpharm.2012.03.054] [PMID: 22503953]
[108]
Park Y, Yong CS, Kim H-M, et al. Effect of sodium chloride on the release, absorption and safety of diclofenac sodium delivered by poloxamer gel. Int J Pharm 2003; 263(1-2): 105-11.
[http://dx.doi.org/10.1016/S0378-5173(03)00362-4] [PMID: 12954185]
[109]
Rangabhatla ASL, Tantishaiyakul V, Oungbho K, Boonrat O. Fabrication of pluronic and methylcellulose for etidronate delivery and their application for osteogenesis. Int J Pharm 2016; 499(1-2): 110-8.
[http://dx.doi.org/10.1016/j.ijpharm.2015.12.070] [PMID: 26748362]
[110]
Chun KW, Lee JB, Kim SH, Park TG. Controlled release of plasmid DNA from photo-cross-linked pluronic hydrogels. Biomaterials 2005; 26(16): 3319-26.
[http://dx.doi.org/10.1016/j.biomaterials.2004.07.055] [PMID: 15603827]
[111]
Chung TW, Lin SY, Liu DZ, Tyan YC, Yang JS. Sustained release of 5-FU from Poloxamer gels interpenetrated by crosslinking chitosan network. Int J Pharm 2009; 382(1-2): 39-44.
[http://dx.doi.org/10.1016/j.ijpharm.2009.07.035] [PMID: 19666095]
[112]
Mao Y, Li X, Chen G, Wang S. Thermosensitive hydrogel system with paclitaxel liposomes used in localized drug delivery system for in situ treatment of tumor: Better antitumor efficacy and lower toxicity. J Pharm Sci 2016; 105(1): 194-204.
[http://dx.doi.org/10.1002/jps.24693] [PMID: 26580704]
[113]
Fakhari A, Corcoran M, Schwarz A. Thermogelling properties of purified poloxamer 407. Heliyon 2017; 3(8): e00390.
[http://dx.doi.org/10.1016/j.heliyon.2017.e00390] [PMID: 28920092]
[114]
Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res 2006; 23(12): 2709-28.
[http://dx.doi.org/10.1007/s11095-006-9104-4] [PMID: 17096184]
[115]
Irimia T, Dinu-Pîrvu CE, Ghica M, et al. Chitosan-based in situ gels for ocular delivery of therapeutics: A state-of-the-art review. Mar Drugs 2018; 16(10): 373.
[http://dx.doi.org/10.3390/md16100373] [PMID: 30304825]
[116]
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.
[http://dx.doi.org/10.1080/17425247.2020.1731469] [PMID: 32067500]
[117]
Lu L, Liu X, Qian L, Tong Z. Sol-gel transition in aqueous alginate solutions induced by cupric cations observed with viscoelasticity. Polym J 2003; 35(10): 804-9.
[http://dx.doi.org/10.1295/polymj.35.804]
[118]
Liu X, Qian L, Shu T, Tong Z. Rheology characterization of sol-gel transition in aqueous alginate solutions induced by calcium cations through in situ release. Polymer 2003; 44(2): 407-12.
[http://dx.doi.org/10.1016/S0032-3861(02)00771-1]
[119]
Phaechamud T, Mahadlek J. Solvent exchange-induced in situ forming gel comprising ethyl cellulose-antimicrobial drugs. Int J Pharm 2015; 494(1): 381-92.
[http://dx.doi.org/10.1016/j.ijpharm.2015.08.047] [PMID: 26302862]
[120]
Cai Z, Song X, Sun F, Yang Z, Hou S, Liu Z. Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin. AAPS PharmSciTech 2011; 12(4): 1102-9.
[http://dx.doi.org/10.1208/s12249-011-9678-y] [PMID: 21879392]
[121]
Perez AP, Mundiña-Weilenmann C, Romero EL, Morilla MJ. Increased brain radioactivity by intranasal P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels. Int J Nanomedicine 2012; 7: 1373-85.
[PMID: 22457595]
[122]
Ahmed TA, El-Say KM, Ahmed OAA, Aljaeid BM. Superiority of TPGS-loaded micelles in the brain delivery of vinpocetine via administration of thermosensitive intranasal gel. Int J Nanomedicine 2019; 14: 5555-67.
[http://dx.doi.org/10.2147/IJN.S213086] [PMID: 31413562]
[123]
Dalvi A, Ravi PR, Uppuluri CT. Rufinamide-loaded chitosan nanoparticles in xyloglucan-based thermoresponsive in situ gel for direct nose to brain delivery. Front Pharmacol 2021; 12: 691936.
[http://dx.doi.org/10.3389/fphar.2021.691936] [PMID: 34234679]
[124]
Mathure D, Sutar AD, Ranpise H, Pawar A, Awasthi R. Preparation and optimization of liposome containing thermosensitive in situ nasal hydrogel system for brain delivery of sumatriptan succinate. Assay Drug Dev Technol 2023; 21(1): 3-16.
[http://dx.doi.org/10.1089/adt.2022.088] [PMID: 36576871]
[125]
Eissa EM, Elkomy MH, Eid HM, et al. Intranasal delivery of granisetron to the brain via nanostructured cubosomes-based in situ gel for improved management of chemotherapy-induced emesis. Pharmaceutics 2022; 14(7): 1374.
[http://dx.doi.org/10.3390/pharmaceutics14071374] [PMID: 35890270]
[126]
Katona G, Sipos B, Budai-Szűcs M, et al. Development of in situ gelling meloxicam-human serum albumin nanoparticle formulation for nose-to-brain application. Pharmaceutics 2021; 13(5): 646.
[http://dx.doi.org/10.3390/pharmaceutics13050646] [PMID: 34062873]
[127]
Xie H, Li L, Sun Y, et al. An available strategy for nasal brain transport of nanocomposite based on PAMAM dendrimers via in situ gel. Nanomaterials 2019; 9(2): 147.
[http://dx.doi.org/10.3390/nano9020147] [PMID: 30682799]
[128]
Sun Y, Li L, Xie H, et al. Primary studies on construction and evaluation of ion-sensitive in situ gel loaded with paeonol-solid lipid nanoparticles for intranasal drug delivery. Int J Nanomedicine 2020; 15: 3137-60.
[http://dx.doi.org/10.2147/IJN.S247935] [PMID: 32440115]
[129]
Taymouri S, Minaiyan M, Ebrahimi F, Tavakoli N. In-vitro and in-vivo evaluation of chitosan-based thermosensitive gel containing lorazepam NLCs for the treatment of status epilepticus. IET Nanobiotechnol 2020; 14(2): 148-54.
[http://dx.doi.org/10.1049/iet-nbt.2019.0156] [PMID: 32433032]
[130]
Elsenosy FM, Abdelbary GA, Elshafeey AH, Elsayed I, Fares AR. Brain targeting of duloxetine hcl via intranasal delivery of loaded cubosomal gel: In vitro characterization, ex vivo permeation, and in vivo biodistribution studies. Int J Nanomedicine 2020; 15: 9517-37.
[http://dx.doi.org/10.2147/IJN.S277352] [PMID: 33324051]
[131]
Nair AB, Chaudhary S, Shah H, et al. Intranasal delivery of darunavir-loaded mucoadhesive in situ gel: Experimental design, in vitro evaluation, and pharmacokinetic studies. Gels 2022; 8(6): 342.
[http://dx.doi.org/10.3390/gels8060342] [PMID: 35735686]
[132]
Chaudhari S, Chatur V. Development of Valproic acid niosomal in situ nasal gel formulation for epilepsy. Indian J Pharmaceut Edu Res 2013; 47(3): 31-41.
[http://dx.doi.org/10.5530/ijper.47.3.6]
[133]
Li JC, Zhang WJ, Zhu JX, et al. Preparation and brain delivery of nasal solid lipid nanoparticles of quetiapine fumarate in situ gel in rat model of schizophrenia. Int J Clin Exp Med 2015; 8(10): 17590-600.
[PMID: 26770349]
[134]
Fahmy UA, Badr-Eldin SM, Ahmed OAA, et al. Intranasal niosomal in situ gel as a promising approach for enhancing flibanserin bioavailability and brain delivery: In vitro optimization and ex vivo/in vivo evaluation. Pharmaceutics 2020; 12(6): 485.
[http://dx.doi.org/10.3390/pharmaceutics12060485] [PMID: 32471119]
[135]
Manda P, Kushwaha AS, Kundu S, Shivakumar HN, Jo SB, Murthy SN. Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain. J Control Release 2016; 224: 69-76.
[http://dx.doi.org/10.1016/j.jconrel.2015.12.044] [PMID: 26732557]
[136]
Gu F, Fan H, Cong Z, Li S, Wang Y, Wu C. Preparation, characterization, and in vivo pharmacokinetics of thermosensitive in situ nasal gel of donepezil hydrochloride. Acta Pharm 2020; 70(3): 411-22.
[http://dx.doi.org/10.2478/acph-2020-0032] [PMID: 32074067]
[137]
Fahmy UA, Ahmed OAA, Badr-Eldin SM, et al. Optimized nanostructured lipid carriers integrated into in situ nasal gel for enhancing brain delivery of flibanserin. Int J Nanomedicine 2020; 15: 5253-64.
[http://dx.doi.org/10.2147/IJN.S258791] [PMID: 32801690]
[138]
El Taweel MM, Aboul-Einien MH, Kassem MA, Elkasabgy NA. Intranasal zolmitriptan-loaded bilosomes with extended nasal mucociliary transit time for direct nose to brain delivery. Pharmaceutics 2021; 13(11): 1828.
[http://dx.doi.org/10.3390/pharmaceutics13111828] [PMID: 34834242]
[139]
Nagaraja S, Basavarajappa GM, Karnati RK, Bakir EM, Pund S. Ion-triggered in situ gelling nanoemulgel as a platform for nose- to-brain delivery of small lipophilic molecules. Pharmaceutics 2021; 13(8): 1216.
[http://dx.doi.org/10.3390/pharmaceutics13081216] [PMID: 34452177]
[140]
Youssef NAHA, Kassem AA, Farid RM, Ismail FA, EL-Massik MAE, Boraie NA. A novel nasal almotriptan loaded solid lipid nanoparticles in mucoadhesive in situ gel formulation for brain targeting: Preparation, characterization and in vivo evaluation. Int J Pharm 2018; 548(1): 609-24.
[http://dx.doi.org/10.1016/j.ijpharm.2018.07.014] [PMID: 30033394]
[141]
Yang M, Zhang Q, Wang Q, et al. Brain-targeting delivery of two peptidylic inhibitors for their combination therapy in transgenic polyglutamine disease mice via intranasal administration. Mol Pharm 2018; 15(12): 5781-92.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00938] [PMID: 30392378]
[142]
Wavikar PR, Vavia PR. Rivastigmine-loaded in situ gelling nanostructured lipid carriers for nose to brain delivery. J Liposome Res 2015; 25(2): 141-9.
[http://dx.doi.org/10.3109/08982104.2014.954129] [PMID: 25203610]
[143]
Wavikar P, Pai R, Vavia P. Nose to brain delivery of rivastigmine by in situ gelling cationic nanostructured lipid carriers: Enhanced brain distribution and pharmacodynamics. J Pharm Sci 2017; 106(12): 3613-22.
[http://dx.doi.org/10.1016/j.xphs.2017.08.024] [PMID: 28923321]
[144]
Wang Q, Wong CH, Chan HYE, Lee WY, Zuo Z. Statistical Design of Experiment (DoE) based development and optimization of DB213 in situ thermosensitive gel for intranasal delivery. Int J Pharm 2018; 539(1-2): 50-7.
[http://dx.doi.org/10.1016/j.ijpharm.2018.01.032] [PMID: 29366939]
[145]
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.
[http://dx.doi.org/10.1016/j.jddst.2020.101778]
[146]
Olson J, Nealy E, DeForest C, Brasel K. Hydrogel compositions and methods for treatement of malignancies. WO2020176790A1, 2022.
[147]
Hoare T, Babar A, Majcher MJ, et al. In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the intranasal delivery of an antipsychotic peptide. J Control Release 2021; 330: 738-52.
[148]
Chung K, Ku T. Compositions and methods relating to reversibly compressible tissue-hydrogel hybrids. WO Patent 2021226198A1, 2021.
[149]
Cui H, Quinones-Hinojosa A. Therapeutic nanofiber hydrogels for local treatment of brain-related diseases. US Patent PCT/US2016/037781, 2021.
[150]
Segura T, Nih LR, Sideris E. Hydrogel for endogenous neuroprogenitor cell recruitment. WO Patent 2017136427, 2021.
[151]
Ahmed TA, Khalid M, Ahmed OA, Aljaeid BM. In situ gelling composition containing tocopherol-loaded micelles as an intranasal drug delivery system. US Patent 10736843B1, 2020.
[152]
Lim T-H. In situ controlled release drug delivery system. WO Patent 2006047279, 2015.
[153]
Langer RS, O'shea T, Slotkin JR, et al. In vivo Therapeutics Corporation, assignee. Peg based hydrogel for peripheral nerve injury applications and compositions and method of use of synthetic hydrogel sealants. US Patent PCT/US2012/067585, 2013.
[154]
Aderibigbe BA. In situ-based gels for nose to brain delivery for the treatment of neurological diseases. Pharmaceutics 2018; 10(2): 40.

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