{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:57:32Z","timestamp":1792623452330,"version":"4.5.0"},"reference-count":70,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Non-invasive central nervous system (CNS) therapies are limited by complex mechanisms and the blood\u2013brain barrier, but nasal delivery offers a promising alternative. The study planned to develop a non-invasive in situ intranasal mucoadhesive thermosensitive gel to deliver CNS-active risperidone via nose-to-brain targeting. Risperidone, a second-generation antipsychotic, has shown efficacy in managing both psychotic and mood-related symptoms. The mucoadhesive gel formulations help to prolong the residence time at the nasal absorption site, thereby facilitating the uptake of the drug. Methods: The poloxamer 407 (18.0% w\/v), HPMC K100M and K15M (0.3\u20130.5% w\/v), and benzalkonium chloride (0.1% v\/v) were used as thermosensitive polymers, a mucoadhesive agent, and a preservative, respectively, for the development of in situ thermosensitive gel. The developed formulations were evaluated for various parameters. Results: The pH, gelation temperature, gelation time, and drug content were found to be 6.20 \u00b1 0.026\u20136.37 \u00b1 0.015, 34.25 \u00b1 1.10\u201337.50 \u00b1 1.05 \u00b0C, 1.65 \u00b1 0.30\u20132.50 \u00b1 0.55 min, and 95.58 \u00b1 2.37\u201398.03 \u00b1 1.68%, respectively. Furthermore, the optimized F3 formulation showed satisfactory gelling capacity (9.52 \u00b1 0.513 h) and an acceptable mucoadhesive strength (1110.65 \u00b1 6.87 dyne\/cm2). Diffusion of the drug through the egg membrane depended on the formulation\u2019s viscosity, and the F3 formulation explained the first-order release kinetics, indicating concentration-dependent drug diffusion with n &lt; 0.45 (0.398) value, indicating the Fickian-diffusion (diffusional case I). The pharmacokinetic study was performed with male Wistar albino rats, and the F3 in situ thermosensitive risperidone gel confirmed significantly (p &lt; 0.05) ~5.4 times higher brain AUC0\u2013\u221e when administered intranasally compared to the oral solution. Conclusions: Based on physicochemical, in vitro, and in vivo parameters, it can be concluded that in situ thermosensitive gel is suitable for administration of risperidone through the nasal route and can enhance patient compliance through ease of application and with less repeated administration.<\/jats:p>","DOI":"10.3390\/ph18060871","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T08:18:06Z","timestamp":1749629886000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Thermosensitive Mucoadhesive Intranasal In Situ Gel of Risperidone for Nose-to-Brain Targeting: Physiochemical and Pharmacokinetics Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Mahendra","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Biotechnology, College of Life and Applied Sciences, Yeungnam University, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Formulation Research and Development, Naari Pharma Private Limited, Sec-5, Rudrapur 263153, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3568-2358","authenticated-orcid":false,"given":"Ramachandran","family":"Vinayagam","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life and Applied Sciences, Yeungnam University, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-8625","authenticated-orcid":false,"given":"Ramachandran","family":"Samivel","sequence":"additional","affiliation":[{"name":"Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.molliq.2013.11.026","article-title":"Solubility of Antipsychotic Drug Risperidone in Transcutol+ Water Co-Solvent Mixtures at 298.15 to 333.15 K","volume":"191","author":"Shakeel","year":"2014","journal-title":"J. Mol. Liq."},{"key":"ref_2","first-page":"226","article-title":"Preparation and In-Vitro Characterization of Risperidone-Cyclodextrin Inclusion Complexes as a Potential Injectable Product","volume":"17","author":"Shukla","year":"2009","journal-title":"DARU"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bavafa, A., Sahab-Negah, S., and Forouzanfar, F. (2025). Nose-to-Brain Targeting of Resveratrol Nanoformulations. Curr. Vasc. Pharmacol.","DOI":"10.2174\/0115701611337079250115071933"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/nep3.42","article-title":"Research Progress on Intranasal Treatment for Parkinson\u2019s Disease","volume":"2","author":"Wen","year":"2024","journal-title":"Neuroprotection"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pinkiewicz, M., Pinkiewicz, M., Walecki, J., Zaczy\u0144ski, A., and Zawadzki, M. (2024). Breaking Barriers in Neuro-Oncology: A Scoping Literature Review on Invasive and Non-Invasive Techniques for Blood\u2013Brain Barrier Disruption. Cancers, 16.","DOI":"10.3390\/cancers16010236"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zheng, X., Yang, J., Hou, Y., Fang, Y., Wu, K., Song, Y., Liu, K., and Zhu, J. (2024). Current Non-Invasive Strategies for Brain Drug Delivery: Overcoming Blood\u2013Brain Barrier Transport. Mol. Biol. Rep., 51.","DOI":"10.1007\/s11033-023-08968-3"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5022","DOI":"10.7150\/thno.98473","article-title":"Intranasal Delivery of Imaging Agents to the Brain","volume":"14","author":"Almahmoud","year":"2024","journal-title":"Theranostics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1080\/09205063.2024.2396721","article-title":"Current Strategic Arsenal and Advances in Nose to Brain Nanotheranostics for Therapeutic Intervention of Glioblastoma Multiforme","volume":"36","author":"Kumar","year":"2025","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Teleanu, R.I., Preda, M.D., Niculescu, A.-G., Vlad\u00e2cenco, O., Radu, C.I., Grumezescu, A.M., and Teleanu, D.M. (2022). Current Strategies to Enhance Delivery of Drugs across the Blood\u2013Brain Barrier. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14050987"},{"key":"ref_10","unstructured":"World Health Organization (2022). Mental Health and COVID-19: Early Evidence of the Pandemic\u2019s Impact: Scientific Brief, 2 March 2022, World Health Organization."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez, A., Estudillo, E., Guzm\u00e1n-Ruiz, M.A., Herrera-Mundo, N., Victoria-Acosta, G., Cort\u00e9s-Malag\u00f3n, E.M., and L\u00f3pez-Ornelas, A. (2025). Nanotechnology to Overcome Blood\u2013Brain Barrier Permeability and Damage in Neurodegenerative Diseases. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17030281"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, J., Wang, T., Dong, J., and Lu, Y. (2025). The Blood\u2013Brain Barriers: Novel Nanocarriers for Central Nervous System Diseases. J. Nanobiotechnology, 23.","DOI":"10.1186\/s12951-025-03247-8"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.3762\/bjnano.15.113","article-title":"Nanotechnological Approaches for Efficient N2B Delivery: From Small-Molecule Drugs to Biopharmaceuticals","volume":"15","author":"Adscheid","year":"2024","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mittal, V., and Yadav, K.S. (2024). Optimizing Nasal Drug Delivery for Peptides, Proteins, and Small Molecules: Strategic Use of Materials and Techniques to Target the CNS. Int. J. Polym. Mater. Polym. Biomater., 1\u201324.","DOI":"10.1080\/00914037.2024.2443165"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/17425247.2021.1823965","article-title":"Management of Epileptic Disorders Using Nanotechnology-Based Strategies for Nose-to-Brain Drug Delivery","volume":"18","author":"Shringarpure","year":"2021","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Montegiove, N., Calzoni, E., Emiliani, C., and Cesaretti, A. (2022). Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases. J. Funct. Biomater., 13.","DOI":"10.3390\/jfb13030125"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/bdd.2400","article-title":"Exploring the Potential of Nasal Drug Delivery for Brain Targeted Therapy: A Detailed Analysis","volume":"45","author":"Ghosh","year":"2024","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105756","DOI":"10.1016\/j.jddst.2024.105756","article-title":"Brain-Targeted Nasal Chrysin Microemulsion for Reducing Oxidative Stress in Parkinson\u2019s Disease: Pharmacodynamic, Biochemical Evaluation and Brain Distribution Studies","volume":"97","author":"Adangale","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ghadiri, M., Young, P.M., and Traini, D. (2019). Strategies to Enhance Drug Absorption via Nasal and Pulmonary Routes. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11030113"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sipos, B., Katona, G., and Cs\u00f3ka, I. (2024). Risperidone-Loaded Nasal Thermosensitive Polymeric Micelles: Quality by Design-Based Formulation Study. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16060703"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Abdallah, M.H., El-Horany, H.E.-S., El-Nahas, H.M., and Ibrahim, T.M. (2023). Tailoring Risperidone-Loaded Glycethosomal in Situ Gels Using Box\u2013Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112521"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106623","DOI":"10.1016\/j.ejps.2023.106623","article-title":"The Prescription Design and Key Properties of Nasal Gel for CNS Drug Delivery: A Review","volume":"192","author":"Wang","year":"2024","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1208\/s12249-023-02700-x","article-title":"Preparation of Tamsulosin Hydrochloride-Loaded Mucoadhesive in Situ Gelling Polymeric Formulation for Nasal Delivery in Geriatrics","volume":"24","author":"Rana","year":"2023","journal-title":"AAPS PharmSciTech"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.2147\/IJN.S445240","article-title":"Fructus xanthii and Magnolia liliiflora Volatile Oils Liposomes-Loaded Thermosensitive in Situ Gel for Allergic Rhinitis Management","volume":"19","author":"Jing","year":"2024","journal-title":"Int. J. Nanomedicine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.2174\/1872211314666210604120619","article-title":"HPMC-a Marvel Polymer for Pharmaceutical Industry-Patent Review","volume":"15","author":"Guarve","year":"2021","journal-title":"Recent. Adv. Drug Deliv. Formul. Former. Recent Pat. Drug Deliv. Formul."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Clementino, A., Climani, G., Bianchera, A., Buttini, F., and Sonvico, F. (2025). Polysaccharides: New Frontiers for Nasal Administration of Medicines. Polysaccharides, 6.","DOI":"10.3390\/polysaccharides6010006"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Khodaverdi, K., Bakhshi, A., Mozafari, M.R., and Naghib, S.M. (2024). A Review of Chitosan-Based Nanocarriers as Drug Delivery Systems for Brain Diseases: Critical Challenges, Outlooks and Promises. Int. J. Biol. Macromol., 278.","DOI":"10.1016\/j.ijbiomac.2024.134962"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.2147\/IJN.S505427","article-title":"Mucoadhesive-to-Mucopenetrating Nanoparticles for Mucosal Drug Delivery: A Mini Review","volume":"20","author":"Zheng","year":"2025","journal-title":"Int. J. Nanomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"El Sisi, A.M., Eissa, E.M., Hassan, A.H.E., Bekhet, M.A., El-Ela, F.I.A., Roh, E.J., Kharshoum, R.M., and Ali, A.A. (2025). Nose-to-Brain Delivery of Chitosan-Grafted Leciplexes for Promoting the Bioavailability and Antidepressant Efficacy of Mirtazapine: In Vitro Assessment and Animal Studies. Pharmaceuticals, 18.","DOI":"10.3390\/ph18010046"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102424","DOI":"10.1016\/j.asej.2023.102424","article-title":"Biopolymer Chitosan: Potential Sources, Extraction Methods, and Emerging Applications","volume":"15","author":"Hisham","year":"2024","journal-title":"Ain Shams Eng. J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Blebea, N.-M., Pu\u0219ca\u0219u, C., Vlad, R.-A., and Hancu, G. (2025). Chitosan-Based Gel Development: Extraction, Gelation Mechanisms, and Biomedical Applications. Gels, 11.","DOI":"10.3390\/gels11040275"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xia, Y., Ma, Z., Wu, X., Wei, H., Zhang, H., Li, G., Qian, Y., Shahriari-Khalaji, M., Hou, K., and Cao, R. (2024). Advances in Stimuli-responsive Chitosan Hydrogels for Drug Delivery Systems. Macromol. Biosci., 24.","DOI":"10.1002\/mabi.202300399"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Edo, G.I., Yousif, E., and Al-Mashhadani, M.H. (2024). Chitosan: An Overview of Biological Activities, Derivatives, Properties, and Current Advancements in Biomedical Applications. Carbohydr. Res., 109199.","DOI":"10.1016\/j.carres.2024.109199"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Omidian, H., Gill, E.J., Dey Chowdhury, S., and Cubeddu, L.X. (2024). Chitosan Nanoparticles for Intranasal Drug Delivery. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16060746"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1080\/01932691.2023.2211144","article-title":"Nasal Mucoadhesive in Situ Gelling Liquid Crystalline Fluid Precursor System of Polyene Antibiotic for Potential Treatment of Localized Sinuses Aspergillosis Post COVID Infection","volume":"45","author":"Shaikh","year":"2024","journal-title":"J. Dispers. Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"183","DOI":"10.22270\/jddt.v10i2-s.4029","article-title":"Nasal in Situ Gel: Novel Approach for Nasal Drug Delivery","volume":"10","author":"Anjali","year":"2020","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Qian, L., Cook, M.T., and Dreiss, C.A. (2025). In Situ Gels for Nasal Delivery: Formulation, Characterization and Applications. Macromol. Mater. Eng., 2400356.","DOI":"10.1002\/mame.202400356"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"122740","DOI":"10.1016\/j.carbpol.2024.122740","article-title":"Enhanced Diabetic Foot Ulcer Treatment with a Chitosan-Based Thermosensitive Hydrogel Loaded Self-Assembled Multi-Functional Nanoparticles for Antibacterial and Angiogenic Effects","volume":"347","author":"Wu","year":"2025","journal-title":"Carbohydr. Polym."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Anggelia, M.R., Cheng, H., and Lin, C. (2024). Thermosensitive Hydrogels as Targeted and Controlled Drug Delivery Systems: Potential Applications in Transplantation. Macromol. Biosci., 24.","DOI":"10.1002\/mabi.202400064"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, K., Xue, K., and Loh, X.J. (2021). Thermo-Responsive Hydrogels: From Recent Progress to Biomedical Applications. Gels, 7.","DOI":"10.3390\/gels7030077"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lin, H., Xie, L., Lv, L., Chen, J., Feng, F., Liu, W., Han, L., and Liu, F. (2023). Intranasally Administered Thermosensitive Gel for Brain-Targeted Delivery of Rhynchophylline to Treat Parkinson\u2019s Disease. Colloids Surf. B Biointerfaces, 222.","DOI":"10.1016\/j.colsurfb.2022.113065"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ijpharm.2014.08.023","article-title":"Enhancement in Bioavailability of Ketorolac Tromethamine via Intranasal in Situ Hydrogel Based on Poloxamer 407 and Carrageenan","volume":"474","author":"Li","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Soni, S., Verma, A., and Ram, V. (2016). Evaluation of Chitosan-Hydroxy Propyl Methyl Cellulose as a Single Unit Hydrodynamically Balanced Sustained Release Matrices for Stomach Specific Delivery of Piroxicam. MOJ Bioequiv Availab., 2.","DOI":"10.15406\/mojbb.2016.01.00014"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Upadhyay, R.K. (2014). Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/869269"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/s41578-021-00394-w","article-title":"Drug Delivery to the Central Nervous System","volume":"7","author":"Nance","year":"2022","journal-title":"Nat. Rev. Mater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"887","DOI":"10.2174\/1567201816666191029122740","article-title":"Drug Delivery and Targeting to the Brain through Nasal Route: Mechanisms, Applications and Challenges","volume":"16","author":"Kashyap","year":"2019","journal-title":"Curr. Drug Deliv."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.brainresbull.2018.10.009","article-title":"Evaluation of Intranasal Delivery Route of Drug Administration for Brain Targeting","volume":"143","author":"Bors","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"121218","DOI":"10.1016\/j.ijpharm.2021.121218","article-title":"Role of Physicochemical Properties of Some Grades of Hydroxypropyl Methylcellulose on in Vitro Mucoadhesion","volume":"609","author":"Zhang","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, X., Shi, X., and Tian, L. (2024). Design of Berberine Hydrochloride Sustained-Release Cold Sol Using Hydroxypropyl Methyl Cellulose K100M to Achieve Superior Drug Dissolution and Transdermal Absorption. Int. J. Biol. Macromol., 275.","DOI":"10.1016\/j.ijbiomac.2024.133611"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1039\/D0TB02877K","article-title":"Recent Advances in Thermo-Sensitive Hydrogels for Drug Delivery","volume":"9","author":"Yu","year":"2021","journal-title":"J. Mater. Chem. B"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Abdallah, M.H., Shahien, M.M., El-Horany, H.E.-S., Ahmed, E.H., El-Nahas, H.M., Abdulla, N.A., and Ibrahim, T.M. (2024). Evaluation of Mucoadhesive Nano-Bilosomal In Situ Gels Containing Anti-Psychotic Clozapine for Treatment of Schizophrenia: In Vitro and In Vivo Studies. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101404"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"95","DOI":"10.31351\/vol28iss2pp95-104","article-title":"Formulation and Evaluation of Sustained Release Sumatriptan Mucoadhesive Intranasal In-Situ Gel","volume":"28","author":"Alkufi","year":"2019","journal-title":"Iraqi J. Pharm. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wang, E., Qi, Z., Cao, Y., Li, R., Wu, J., Tang, R., Gao, Y., Du, R., and Liu, M. (2025). Gels as Promising Delivery Systems: Physicochemical Property Characterization and Recent Applications. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17020249"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6401267","DOI":"10.1155\/2016\/6401267","article-title":"Optimization of Thermoreversible in Situ Nasal Gel of Timolol Maleate","volume":"2016","author":"Jagdale","year":"2016","journal-title":"Scientifica"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Abdeltawab, H., Svirskis, D., Hill, A.G., and Sharma, M. (2022). Increasing the Hydrophobic Component of Poloxamers and the Inclusion of Salt Extend the Release of Bupivacaine from Injectable In Situ Gels, While Common Polymer Additives Have Little Effect. Gels, 8.","DOI":"10.3390\/gels8080484"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/17425247.2020.1731469","article-title":"Formulation Strategies to Modulate Drug Release from Poloxamer Based in Situ Gelling Systems","volume":"17","author":"Abdeltawab","year":"2020","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3109\/10837450.2011.609991","article-title":"The Influence of HPMC Viscosity as FRC Parameter on the Release of Low Soluble Drug from Hydrophylic Matrix Tablets","volume":"18","author":"Novak","year":"2013","journal-title":"Pharm. Dev. Technol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3109\/10717544.2012.704095","article-title":"Thermally Reversible Xyloglucan Gels as Vehicles for Nasal Drug Delivery","volume":"19","author":"Mahajan","year":"2012","journal-title":"Drug Deliv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3109\/10717544.2013.849778","article-title":"Development of in Situ Gel for Nasal Delivery: Design, Optimization, in Vitro and in Vivo Evaluation","volume":"21","author":"Galgatte","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Pan, P., Svirskis, D., Waterhouse, G.I.N., and Wu, Z. (2023). Hydroxypropyl Methylcellulose Bioadhesive Hydrogels for Topical Application and Sustained Drug Release: The Effect of Polyvinylpyrrolidone on the Physicomechanical Properties of Hydrogel. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15092360"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Tripathi, M., Gharti, L., Bansal, A., Kaurav, H., and Sheth, S. (2025). Intranasal Mucoadhesive In Situ Gel of Glibenclamide-Loaded Bilosomes for Enhanced Therapeutic Drug Delivery to the Brain. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17020193"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s40005-020-00486-9","article-title":"Comparison of Solubility Enhancement by Solid Dispersion and Micronized Butein and Its Correlation with in Vivo Study","volume":"51","author":"Kim","year":"2021","journal-title":"J. Pharm. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Bajracharya, R., Lee, S.H., Song, J.G., Kim, M., Lee, K., and Han, H.-K. (2019). Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the in Vivo Activity as a BCRP Inhibitor: Preparation and in Vitro\/in Vivo Characterization. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050206"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"120245","DOI":"10.1016\/j.ijpharm.2021.120245","article-title":"Third-Generation Solid Dispersion Combining Soluplus and Poloxamer 407 Enhances the Oral Bioavailability of Resveratrol","volume":"595","author":"Vasconcelos","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/0122117385285009231222072303","article-title":"Preparation, in-Vitro, Ex-Vivo, and Pharmacokinetic Study of Lasmiditan as Intranasal Nanoemulsion-Based in Situ Gel","volume":"13","author":"Jabir","year":"2025","journal-title":"Pharm. Nanotechnol."},{"key":"ref_66","first-page":"1167","article-title":"In Situ Nasal Gel Drug Delivery: A Novel Approach for Brain Targeting through the Mucosal Membrane","volume":"44","author":"Kaur","year":"2016","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4103\/2230-973X.108961","article-title":"Formulation and Evaluation of Periodontal in Situ Gel","volume":"3","author":"Garala","year":"2013","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"101602","DOI":"10.1039\/C6RA20896G","article-title":"Development of an \u03b1-Linolenic Acid Containing a Soft Nanocarrier for Oral Delivery-Part II: Buccoadhesive Gel","volume":"6","author":"Singh","year":"2016","journal-title":"RSC Adv."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1007\/s12668-023-01290-z","article-title":"Fabrication of PF-127 Based Niosomal in Situ Gel for Intranasal Delivery of Lurasidone Hydrochloride and Optimization by Using 32 Factorial Design","volume":"14","author":"Shikalgar","year":"2024","journal-title":"Bionanoscience"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1515\/acph-2016-0047","article-title":"Preparation and in Vivo Evaluation of Gel-Based Nasal Delivery System for Risperidone","volume":"66","author":"Gu","year":"2016","journal-title":"Acta Pharmaceutica"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/6\/871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:50:09Z","timestamp":1760032209000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/6\/871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":70,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ph18060871"],"URL":"https:\/\/doi.org\/10.3390\/ph18060871","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}