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The current oral formulations of DPZ demonstrate decreased bioavailability, attributed to limited drug permeability across the blood\u2013brain barrier (BBB). In order to overcome these limitations, various dosage forms aimed at delivering DPZ have been explored. This discussion will focus on the nose-to-brain (N2B) delivery system, which represents the most promising approach for brain drug delivery. Intranasal (IN) drug delivery is a suitable system for directly delivering drugs to the brain, as it bypasses the BBB and avoids the first-pass effect, thereby targeting the central nervous system (CNS). Currently developed formulations include lipid-based, solid particle-based, solution-based, gel-based, and film-based types, and a systematic review of the N2B research related to these formulations has been conducted. According to the in vivo results, the brain drug concentration 15 min after IN administration was more than twice as high those from other routes of administration, and the direct delivery ratio of the N2B system improved to 80.32%. The research findings collectively suggest low toxicity and high therapeutic efficacy for AD. This review examines drug formulations and delivery methods optimized for the N2B delivery of DPZ, focusing on technologies that enhance mucosal residence time and bioavailability while discussing recent advancements in the field.<\/jats:p>","DOI":"10.3390\/pharmaceutics17080958","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:19:22Z","timestamp":1753370362000},"page":"958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Recent Advances in Donepezil Delivery Systems via the Nose-to-Brain Pathway"],"prefix":"10.3390","volume":"17","author":[{"given":"Jiyoon","family":"Jon","sequence":"first","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9124-9052","authenticated-orcid":false,"given":"Joohee","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9131-5742","authenticated-orcid":false,"given":"Hyosun","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3123-5745","authenticated-orcid":false,"given":"Kyoung","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6205-1794","authenticated-orcid":false,"given":"Eun-Sook","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-7353","authenticated-orcid":false,"given":"Sang Hyup","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunyoung","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Hyun","family":"Chung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aree","family":"Moon","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5163-0262","authenticated-orcid":false,"given":"Kyu-Tae","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejun","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jconrel.2018.05.011","article-title":"Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs","volume":"281","author":"Agrawal","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0301-0082(97)00028-2","article-title":"The cholinergic system in Alzheimer\u2019s disease","volume":"52","author":"Rakonczay","year":"1997","journal-title":"Prog. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Thornton, S., and Crane, T. (2020). Laboratory confirmed massive donepezil ingestion. Toxicology Cases for the Clinical and Forensic Laboratory, Elsevier.","DOI":"10.1016\/B978-0-12-815846-3.00095-8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1126\/science.7046051","article-title":"The cholinergic hypothesis of geriatric memory dysfunction","volume":"217","author":"Bartus","year":"1982","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1126\/science.7058341","article-title":"Alzheimer\u2019s disease and senile dementia: Loss of neurons in the basal forebrain","volume":"215","author":"Whitehouse","year":"1982","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102549","DOI":"10.1016\/j.jddst.2021.102549","article-title":"Donepezil\u2014An updated review of challenges in dosage form design","volume":"63","author":"Sutthapitaksakul","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1389557513666131119201353","article-title":"Donepezil: An important prototype to the design of new drug candidates for Alzheimer\u2019s disease","volume":"14","author":"Viegas","year":"2014","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1254\/jjp.89.7","article-title":"Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor","volume":"89","author":"Sugimoto","year":"2002","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_9","first-page":"CD011546","article-title":"Pharmacological interventions for cognitive decline in people with Down syndrome","volume":"2015","author":"Livingstone","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_10","first-page":"CD007178","article-title":"Donepezil for dementia in people with Down syndrome","volume":"2009","author":"Mohan","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13195-018-0363-1","article-title":"A double-blind placebo-controlled cross-over clinical trial of DONepezil in Posterior cortical atrophy due to underlying Alzheimer\u2019s Disease: DONIPAD study","volume":"10","author":"Ridha","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.jagp.2018.05.008","article-title":"Donepezil treatment in patients with depression and cognitive impairment on stable antidepressant treatment: A randomized controlled trial","volume":"26","author":"Devanand","year":"2018","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1517\/14656566.5.1.161","article-title":"Donepezil: A clinical review of current and emerging indications","volume":"5","author":"Rogers","year":"2004","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ijpharm.2013.05.029","article-title":"A novel electronic skin patch for delivery and pharmacokinetic evaluation of donepezil following transdermal iontophoresis","volume":"453","author":"Saluja","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_15","unstructured":"Moffat, A.C., Osselton, M.D., Widdop, B., and Watts, J. (2011). Clarke\u2019s Analysis of Drugs and Poisons, Pharmaceutical Press."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S1871-5125(10)35003-5","article-title":"Donepezil","volume":"Volume 35","author":"Asiri","year":"2021","journal-title":"Profiles of Drug Substances, Excipients and Related Methodology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.xphs.2015.10.016","article-title":"Exploring the phase behavior of monoolein\/oleic acid\/water systems for enhanced donezepil administration for Alzheimer disease treatment","volume":"105","author":"Ruela","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1159\/000338236","article-title":"Efficacy and safety of donepezil 23 mg versus donepezil 10 mg for moderate-to-severe Alzheimer\u2019s disease: A subgroup analysis in patients already taking or not taking concomitant memantine","volume":"33","author":"Doody","year":"2012","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_19","first-page":"742","article-title":"Donepezil to manage Alzheimer disease: New vs. standard Dosing","volume":"83","author":"Graber","year":"2011","journal-title":"Am. Fam. Physician"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.pharmthera.2004.08.001","article-title":"Delivery of therapeutic agents to the central nervous system: The problems and the possibilities","volume":"104","author":"Begley","year":"2004","journal-title":"Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.pneurobio.2008.12.002","article-title":"Delivery of peptide and protein drugs over the blood\u2013brain barrier","volume":"87","author":"Brasnjevic","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1517\/17425247.3.3.419","article-title":"Drug delivery across the blood\u2013brain barrier: Why is it difficult? How to measure and improve it?","volume":"3","author":"Su","year":"2006","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jconrel.2017.05.019","article-title":"Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer\u2019s disease","volume":"260","author":"Agrawal","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.addr.2011.12.005","article-title":"Drug delivery to the brain in Alzheimer\u2019s disease: Consideration of the blood\u2013brain barrier","volume":"64","author":"Banks","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40035-025-00481-w","article-title":"Nose-to-brain drug delivery: From bench to bedside","volume":"14","author":"Drath","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1002\/jps.21895","article-title":"Evidence of carrier-mediated transport in the penetration of donepezil into the rat brain","volume":"99","author":"Kim","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Drapaca, C.S. (2024). Mathematical Modeling of Alzheimer\u2019s Drug Donepezil Hydrochloride Transport to the Brain after Oral Administration. Fractal Fract., 8.","DOI":"10.3390\/fractalfract8090496"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s40005-021-00556-6","article-title":"Tableting process-induced solid-state polymorphic transition","volume":"52","author":"Park","year":"2022","journal-title":"J. Pharm. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s40005-024-00714-6","article-title":"A comprehensive review of oral disintegrating film products, and their quality assessment and development","volume":"55","author":"Nam","year":"2025","journal-title":"J. Pharm. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3144\/expresspolymlett.2010.92","article-title":"Electrospun water soluble polymer mat for ultrafast release of Donepezil HCl","volume":"4","author":"Nagy","year":"2010","journal-title":"Express Polym. Lett."},{"key":"ref_31","first-page":"451","article-title":"Orally disintegrating donepezil: Are the main caregivers of patients with Alzheimer\u2019s disease more satisfied with this formulation of donepezil than with the traditional one?","volume":"49","author":"Sevilla","year":"2009","journal-title":"Rev. De Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1021\/acs.molpharmaceut.1c00290","article-title":"An Update on the Routes for the Delivery of Donepezil","volume":"18","author":"Zhao","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_33","unstructured":"(2025, May 25). Ministry of Food and Drug Safety. Available online: https:\/\/nedrug.mfds.go.kr\/eng\/index."},{"key":"ref_34","first-page":"533","article-title":"A Comprehensive Review on Complexities and Directions of Drug Delivery Using Transdermal Patches","volume":"2","author":"Gowsalya","year":"2024","journal-title":"Int. J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102007","DOI":"10.1016\/j.jddst.2020.102007","article-title":"Transdermal delivery of peptide and protein drugs: Strategies, advantages and disadvantages","volume":"60","author":"Long","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_36","first-page":"379","article-title":"Transdermal drug delivery\u2014A review","volume":"3","author":"Gandhi","year":"2012","journal-title":"Int. J. Res. Pharm. Sci."},{"key":"ref_37","first-page":"361","article-title":"Transdermal donepezil on the treatment of Alzheimer\u2019s disease","volume":"8","author":"Sozio","year":"2012","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_38","unstructured":"Valia, K.H., and Ramaraju, V.S. (2016). Transdermal Methods and Systems for Treating Alzheimer\u2019s Disease. (No. 9,248,104), U.S. Patent."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3109\/03639045.2011.561352","article-title":"Effects of vehicles on the percutaneous absorption of donepezil hydrochloride across the excised hairless mouse skin","volume":"37","author":"Kim","year":"2011","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1208\/s12249-014-0224-6","article-title":"Biopolymer-based transdermal films of donepezil as an alternative delivery approach in Alzheimer\u2019s disease treatment","volume":"16","author":"Erdal","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4103\/0253-7613.208143","article-title":"Current advances in transdermal delivery of drugs for Alzheimer\u2019s disease","volume":"49","author":"Nguyen","year":"2017","journal-title":"Indian J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3390\/pharmaceutics7040438","article-title":"Transdermal drug delivery: Innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum","volume":"7","author":"McCrudden","year":"2015","journal-title":"Pharmaceutics"},{"key":"ref_43","first-page":"283","article-title":"Effect of several factors on the mechanical properties of a pressure sensitive adhesive containing penetration enhancers","volume":"12","author":"Kyriazanou","year":"2002","journal-title":"STP Pharma Sci."},{"key":"ref_44","unstructured":"Sheth, N.S., and Mistry, R.B. (2011). Formulation and evaluation of transdermal patches and to study permeation enhancement effect of eugenol. J. Appl. Pharm. Sci., 96\u2013101."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5","DOI":"10.22159\/ajpcr.2017.v10i9.19389","article-title":"Natural permeation enhancer for transdermal drug delivery system and permeation evaluation: A review","volume":"10","author":"Das","year":"2017","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_46","first-page":"1001","article-title":"Review article on permeation enhancers: A major breakthrough in drug delivery technology","volume":"8","author":"Roy","year":"2017","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ejpb.2016.06.006","article-title":"Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer\u2019s disease","volume":"105","author":"Kim","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.2174\/0929867324666170526124053","article-title":"Microneedle patches as drug and vaccine delivery platform","volume":"24","author":"Li","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.biopha.2018.10.078","article-title":"Microneedles: A smart approach and increasing potential for transdermal drug delivery system","volume":"109","author":"Waghule","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3390\/pharmaceutics7030090","article-title":"Transdermal delivery of drugs with microneedles\u2014Potential and challenges","volume":"7","author":"Ita","year":"2015","journal-title":"Pharmaceutics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1053\/apnr.2002.34142","article-title":"Intramuscular injection: An integrative research review and guideline for evidence-based practice","volume":"15","author":"Nicoll","year":"2002","journal-title":"Appl. Nurs. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1365-2850.2007.01236.x","article-title":"Intramuscular injections: A review of best practice for mental health nurses","volume":"15","author":"Cocoman","year":"2008","journal-title":"J. Psychiatr. Ment. Health Nurs."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1212\/01.wnl.0000281846.40390.50","article-title":"Pharmacokinetic rationale for the rivastigmine patch","volume":"69","author":"Cummings","year":"2007","journal-title":"Neurology"},{"key":"ref_54","first-page":"405","article-title":"Sustained release donepezil loaded PLGA microspheres for injection: Preparation, In Vitro and In Vivo study","volume":"10","author":"Guo","year":"2015","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijpharm.2016.02.023","article-title":"Sustained release of risperidone from biodegradable microspheres prepared by in-situ suspension-evaporation process","volume":"503","author":"An","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1016\/S0142-9612(03)00161-3","article-title":"Biocompatibility of implantable synthetic polymeric drug carriers: Focus on brain biocompatibility","volume":"24","author":"Fournier","year":"2003","journal-title":"Biomaterials"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ijpharm.2018.07.013","article-title":"In-situ forming PLGA implants for intraocular dexamethasone delivery","volume":"548","author":"Bode","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1002\/adfm.201103059","article-title":"Multicomponent organic nanoparticles for fluorescence studies in biological systems","volume":"22","author":"McDonald","year":"2012","journal-title":"Adv. Funct. Mater."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"24744","DOI":"10.1039\/c2jm34974d","article-title":"Facile synthesis of complex multi-component organic and organic\u2013magnetic inorganic nanocomposite particles","volume":"22","author":"Giardiello","year":"2012","journal-title":"J. Mater. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.jconrel.2012.04.016","article-title":"In situ forming implants\u2014An attractive formulation principle for parenteral depot formulations","volume":"161","author":"Kempe","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jcis.2013.12.024","article-title":"The effect of oil type on the aggregation stability of nanostructured lipid carriers","volume":"418","author":"Yang","year":"2014","journal-title":"J. Colloid Interface Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"217","DOI":"10.5731\/pdajpst.2011.00693","article-title":"Risk analysis of sterile production plants: A new and simple, workable approach","volume":"65","author":"Gapp","year":"2011","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1208\/s12249-011-9617-y","article-title":"Development of biotechnology products in pre-filled syringes: Technical considerations and approaches","volume":"12","author":"Badkar","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.addr.2016.02.003","article-title":"Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy","volume":"103","author":"Owen","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.colsurfb.2014.06.037","article-title":"Surface engineered nanostructured lipid carriers for efficient nose to brain delivery of ondansetron HCl using Delonix regia gum as a natural mucoadhesive polymer","volume":"122","author":"Devkar","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1080\/08982104.2018.1552703","article-title":"Nanostructured cubosomes in an in situ nasal gel system: An alternative approach for the controlled delivery of donepezil HCl to brain","volume":"29","author":"Patil","year":"2019","journal-title":"J. Liposome Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jconrel.2023.12.054","article-title":"Nanotechnology for enhanced nose-to-brain drug delivery in treating neurological diseases","volume":"366","author":"Huang","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"29779","DOI":"10.1021\/acsnano.4c09449","article-title":"Intranasal Carrier-Free Nanomodulator Addresses Both Symptomatology and Etiology of Alzheimer\u2019s Disease by Restoring Neuron Plasticity and Reprogramming Lesion Microenvironment","volume":"18","author":"Yang","year":"2024","journal-title":"ACS Nano"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Espinoza, L.C., Silva-Abreu, M., Clares, B., Rodr\u00edguez-Lagunas, M.J., Halbaut, L., Ca\u00f1as, M.-A., and Calpena, A.C. (2019). Formulation strategies to improve nose-to-brain delivery of donepezil. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020064"},{"key":"ref_70","unstructured":"Frey William, I.H. (1991). Neurologic Agents for Nasal Administration to the Brain. (Patent WO1991007947A1)."},{"key":"ref_71","unstructured":"Frey, L.W.H., Danielyan, L., and Gleiter, C.H. (2016). Methods, Pharmaceutical Compositions and Articles of Manufacture for Administering Therapeutic Cells to the Animal Central Nervous System. (No. 9,445,991), U.S. Patent."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s40005-020-00482-z","article-title":"Factors influencing drug deposition in the nasal cavity upon delivery via nasal sprays","volume":"50","author":"Gao","year":"2020","journal-title":"J. Pharm. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.lfs.2017.12.025","article-title":"Mechanism of intranasal drug delivery directly to the brain","volume":"195","author":"Crowe","year":"2018","journal-title":"Life Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/jps.20480","article-title":"Intranasal mucoadhesive microemulsions of clonazepam: Preliminary studies on brain targeting","volume":"95","author":"Vyas","year":"2006","journal-title":"J. Pharm. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Duong, V.-A., Nguyen, T.-T.-L., and Maeng, H.-J. (2023). Recent advances in intranasal liposomes for drug, gene, and vaccine delivery. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010207"},{"key":"ref_76","first-page":"40","article-title":"Intranasal drug delivery bypasses the blood\u2013brain barrier","volume":"24","author":"Frey","year":"2016","journal-title":"Neurol. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3233\/JAD-142421","article-title":"Nasal application of the galantamine pro-drug memogain slows down plaque deposition and ameliorates behavior in 5X familial Alzheimer\u2019s disease mice","volume":"46","author":"Bhattacharya","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/17425247.2025.2464714","article-title":"Bringing intranasal drug delivery for malignancies in the brain to market","volume":"22","author":"Chen","year":"2025","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/s11064-021-03488-7","article-title":"Lipid-based nanocarriers via nose-to-brain pathway for central nervous system disorders","volume":"47","author":"Nguyen","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/17425247.2025.2470224","article-title":"Transmucosal drug delivery: Prospects, challenges, advances, and future directions","volume":"22","author":"Brako","year":"2025","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ijpharm.2013.05.009","article-title":"Enhanced brain distribution and pharmacodynamics of rivastigmine by liposomes following intranasal administration","volume":"452","author":"Yang","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1530\/rep.1.00278","article-title":"Counter-current transfer in reproductive biology","volume":"129","author":"Hunter","year":"2005","journal-title":"Reproduction"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0928-0987(00)00087-7","article-title":"Transport of drugs from the nasal cavity to the central nervous system","volume":"11","author":"Illum","year":"2000","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s40005-022-00589-5","article-title":"Drug delivery to the brain via the nasal route of administration: Exploration of key targets and major consideration factors","volume":"53","author":"Jeong","year":"2023","journal-title":"J. Pharm. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.ijbiomac.2014.03.022","article-title":"Donepezil nanosuspension intended for nose to brain targeting: In Vitro and In Vivo safety evaluation","volume":"67","author":"Md","year":"2014","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/jps.21924","article-title":"Intranasal delivery to the central nervous system: Mechanisms and experimental considerations","volume":"99","author":"Dhuria","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jconrel.2012.09.017","article-title":"Approaches for breaking the barriers of drug permeation through transdermal drug delivery","volume":"164","author":"Alexander","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1023\/A:1012029517394","article-title":"The oral absorption of micro-and nanoparticulates: Neither exceptional nor unusual","volume":"14","author":"Florence","year":"1997","journal-title":"Pharm. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1081\/DDC-120001481","article-title":"Nanoparticle technology for drug delivery across the blood-brain barrier","volume":"28","author":"Lockman","year":"2002","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1211\/0022357011775145","article-title":"The biopharmaceutical aspects of nasal mucoadhesive drug delivery","volume":"53","author":"Ugwoke","year":"2001","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/10611860310001640075","article-title":"Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous delivery in rats and humans","volume":"11","author":"Merkus","year":"2003","journal-title":"J. Drug Target."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1208\/pt030105","article-title":"Targeted brain delivery of 17\u03b2-estradiol via nasally administered water soluble prodrugs","volume":"3","author":"Traboulsi","year":"2002","journal-title":"AAPS PharmSciTech"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2404234","DOI":"10.1002\/adfm.202404234","article-title":"Lipid Nanoparticles: Versatile Drug Delivery Vehicles for Traversing the Blood Brain Barrier to Treat Brain Cancer","volume":"34","author":"Cai","year":"2024","journal-title":"Adv. Funct. Mater."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.apsb.2021.02.012","article-title":"Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of In Vivo studies","volume":"11","author":"Costa","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"John, R., Monpara, J., Swaminathan, S., and Kalhapure, R. (2024). Chemistry and Art of Developing Lipid Nanoparticles for Biologics Delivery: Focus on Development and Scale-Up. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16010131"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Seo, Y., Lim, H., Park, H., Yu, J., An, J., Yoo, H.Y., and Lee, T. (2023). Recent progress of lipid nanoparticles-based lipophilic drug delivery: Focus on surface modifications. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030772"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1007\/s13346-020-00754-z","article-title":"Treatment of Alzheimer\u2019s diseases using donepezil nanoemulsion: An intranasal approach","volume":"10","author":"Kaur","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4714","DOI":"10.1021\/acs.molpharmaceut.3c00454","article-title":"Simultaneous intranasal codelivery of donepezil and memantine in a nanocolloidal carrier: Optimization, pharmacokinetics, and pharmacodynamics studies","volume":"20","author":"Handa","year":"2023","journal-title":"Mol. Pharm."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2174\/1871527317666180104122347","article-title":"Development of a Nasal Donepezil-loaded Microemulsion for the Treatment of Alzheimer\u2019s Disease: In Vitro and Ex Vivo Characterization","volume":"17","author":"Espinoza","year":"2018","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1208\/s12249-019-1585-7","article-title":"Role of omega-3 fatty acids and butter oil in targeting delivery of donepezil hydrochloride microemulsion to brain via the intranasal route: A comparative study","volume":"21","author":"Khunt","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2147\/DDDT.S93937","article-title":"Preparation, characterization, and In Vivo evaluation of intranasally administered liposomal formulation of donepezil","volume":"10","author":"Ullah","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1208\/s12249-022-02209-9","article-title":"Donepezil HCl liposomes: Development, characterization, cytotoxicity, and pharmacokinetic study","volume":"23","author":"Rajput","year":"2022","journal-title":"AAPS PharmSciTech"},{"key":"ref_103","first-page":"1934","article-title":"Nose-to-Brain Targeted Delivery of Donepezil Hydrochloride via Novel Hyaluronic Acid-Doped Nanotransfersomes for Alzheimer\u2019s Disease Mitigation","volume":"113","author":"Salem","year":"2024","journal-title":"J. Pharm. Sci."},{"key":"ref_104","first-page":"1838","article-title":"Solid lipid nanoparticles for nose to brain delivery of donepezil: Formulation, optimization by Box\u2013Behnken design, In Vitro and In Vivo evaluation","volume":"46","author":"Yasir","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e22330","DOI":"10.1590\/s2175-97902023e22330","article-title":"Investigation on formulation parameters of donepezil HCl loaded solid lipid nanoparticles","volume":"59","author":"Topal","year":"2023","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.5958\/0974-360X.2018.00523.1","article-title":"Formulation and evaluation of glyceryl behenate based solid lipid nanoparticles for the delivery of donepezil to brain through nasal route","volume":"11","author":"Yasir","year":"2018","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"103631","DOI":"10.1016\/j.jddst.2022.103631","article-title":"Nose to brain delivery of donepezil through surface modified NLCs: Formulation development, optimization, and brain targeting study","volume":"75","author":"Yasir","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s10876-023-02531-7","article-title":"Donepezil and Embelin loaded nanostructured lipid carriers for direct brain delivery as an intervention for Alzheimer\u2019s disease: Formulation design, optimization and evaluation","volume":"35","author":"Ali","year":"2024","journal-title":"J. Clust. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1080\/03639045.2023.2262035","article-title":"Design and development of donepezil hydrochloride loaded nanostructured lipid carriers for efficient management of Alzheimer\u2019s disease","volume":"49","author":"Tekade","year":"2023","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.2147\/IJN.S417928","article-title":"Combined donepezil with astaxanthin via nanostructured lipid carriers effective delivery to brain for Alzheimer\u2019s disease in rat model","volume":"18","author":"Shehata","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Bhandari, M., Rasool, N., and Singh, Y. (2022). Polymeric lipid nanoparticles for donepezil delivery. Polymeric Biomaterials and Bioengineering: Select Proceedings of APA Bioforum 2021, Springer.","DOI":"10.1007\/978-981-19-1084-5_5"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"111721","DOI":"10.1016\/j.colsurfb.2021.111721","article-title":"The liquid crystalline phase behaviour of a nasal formulation modifies the brain disposition of donepezil in rats in the treatment of Alzheimer\u2019s disease","volume":"203","author":"Placido","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s10876-024-02608-x","article-title":"Optimization, characterization and In-Vitro cellular uptake of donepezil-loaded nanocrystvesicles","volume":"35","author":"Dhiman","year":"2024","journal-title":"J. Clust. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"935","DOI":"10.5530\/ijper.54.4.187","article-title":"Development of donepezil hydrochloride loaded gellan gum based nasal mucoadhesive microspheres by spray drying method","volume":"54","author":"Gangane","year":"2020","journal-title":"Indian J. Pharm. Educ. Res"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"122038","DOI":"10.1016\/j.ijpharm.2022.122038","article-title":"Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery","volume":"624","author":"Nodilo","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"105","DOI":"10.31782\/IJCRR.2020.121929","article-title":"Gellan gum assisted fabrication and characterization of donepezil hydrochloride mucoadhesive intranasal microspheres","volume":"12","author":"Gangane","year":"2020","journal-title":"Int. J. Curr. Res. Rev"},{"key":"ref_117","first-page":"948","article-title":"Formulation and evaluation of nasal mucoadhesive microsphers by solvent evaporation technique","volume":"9","author":"Ambadkar","year":"2020","journal-title":"World J. Pharm. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"205","DOI":"10.5530\/ijpi.2022.2.36","article-title":"Spray Dried Mucoadhesive Microparticles of Donepezil with Chitosan and Carbopol in Alzheimer\u2019s Disease","volume":"12","author":"Jadhav","year":"2022","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"213663","DOI":"10.1016\/j.bioadv.2023.213663","article-title":"Combining donepezil and memantine via mannosylated PLGA nanoparticles for intranasal delivery: Characterization and preclinical studies","volume":"154","author":"Handa","year":"2023","journal-title":"Biomater. Adv."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3109\/03639045.2012.758130","article-title":"Preparation, characterization, In Vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting","volume":"40","author":"Bhavna","year":"2014","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_121","unstructured":"Garg, Y., Sharma, G., Katare, O.P., Chopra, S., and Bhatia, A. (2025, July 20). Design and Optimization of Donepezil Hydrochloride Loaded Nanoparticles Using Doe Approach: A Novel Approach for Treating Alzheimer\u2019s Diseases Through Nose-To-Brain Delivery. Available at SSRN 4255393. Available online: https:\/\/ssrn.com\/abstract=4255393."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Espinoza, L.C., Guaya, D., Calpena, A.C., Perotti, R.M., Halbaut, L., Sosa, L., Brito-Llera, A., and Mallandrich, M. (2022). Comparative study of donepezil-loaded formulations for the treatment of Alzheimer\u2019s disease by nasal administration. Gels, 8.","DOI":"10.3390\/gels8110715"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s10876-023-02528-2","article-title":"Systematic designing and optimization of polymeric nanoparticles using central composite design: A novel approach for nose-to-brain delivery of donepezil hydrochloride","volume":"35","author":"Garg","year":"2024","journal-title":"J. Clust. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e069264","DOI":"10.1002\/alz.069264","article-title":"Treating Alzheimer\u2019s Disease via Donepezil Hydrochloride Loaded Nanoparticles: A Novel Approach for Brain Drug Delivery","volume":"18","author":"Garg","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"430","DOI":"10.2133\/dmpk.DMPK-10-RG-049","article-title":"Lack of a primary physicochemical determinant in the direct transport of drugs to the brain after nasal administration in rats: Potential involvement of transporters in the pathway","volume":"25","author":"Lee","year":"2010","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_126","first-page":"293","article-title":"Fabrication of an ion-sensitive in situ gel loaded with nanostructured lipid carrier for nose to brain delivery of donepezil","volume":"12","author":"Butani","year":"2018","journal-title":"Asian J. Pharm. (AJP)"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"9563","DOI":"10.1038\/s41598-019-46032-y","article-title":"Nasal delivery of donepezil HCl-loaded hydrogels for the treatment of Alzheimer\u2019s disease","volume":"9","author":"Alavi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/s12247-022-09636-y","article-title":"Development and evaluation of thermoreversible ethosomal gel of donepezil hydrochloride for intranasal delivery","volume":"18","author":"Gangopadhyay","year":"2023","journal-title":"J. Pharm. Innov."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"411","DOI":"10.2478\/acph-2020-0032","article-title":"Preparation, characterization, and In Vivo pharmacokinetics of thermosensitive s nasal gel of donepezil hydrochloride","volume":"70","author":"Gu","year":"2020","journal-title":"Acta Pharm."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Perku\u0161i\u0107, M., Ni\u017ei\u0107 Nodilo, L., Ugrina, I., \u0160poljari\u0107, D., Jakobu\u0161i\u0107 Brala, C., Pepi\u0107, I., Lovri\u0107, J., Safund\u017ei\u0107 Ku\u010duk, M., Trenkel, M., and Scherlie\u00df, R. (2023). Chitosan-based thermogelling system for nose-to-brain donepezil delivery: Optimising formulation properties and nasal deposition profile. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061660"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Adnet, T., Groo, A.-C., Picard, C., Davis, A., Corvaisier, S., Since, M., Bounoure, F., Rochais, C., Le Pluart, L., and Dallemagne, P. (2020). Pharmacotechnical development of a nasal drug delivery composite nanosystem intended for Alzheimer\u2019s disease treatment. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030251"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Papakyriakopoulou, P., Rekkas, D.M., Colombo, G., and Valsami, G. (2022). Development and In Vitro-Ex Vivo evaluation of novel polymeric nasal donepezil films for potential use in Alzheimer\u2019s disease using experimental design. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081742"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Kaikousidis, C., Papakyriakopoulou, P., Dokoumetzidis, A., and Valsami, G. (2023). Donepezil brain and blood pharmacokinetic modeling after nasal film and oral solution administration in mice. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051409"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"104463","DOI":"10.1016\/j.jddst.2023.104463","article-title":"Nose-to-Brain delivery of donepezil hydrochloride following administration of an HPMC-Me-\u03b2-CD-PEG400 nasal film in mice","volume":"84","author":"Papakyriakopoulou","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s40005-021-00528-w","article-title":"Microemulsion as a promising carrier for nose to brain delivery: Journey since last decade","volume":"51","author":"Shah","year":"2021","journal-title":"J. Pharm. Investig."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/s41578-019-0161-9","article-title":"Multiple nanoemulsions","volume":"5","author":"Sheth","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"130604","DOI":"10.1016\/j.fuel.2023.130604","article-title":"Effects of emulsification factors on the characteristics of crude oil emulsions stabilized by chemical and Biosurfactants: A review","volume":"361","author":"Onaizi","year":"2024","journal-title":"Fuel"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.foodchem.2013.09.088","article-title":"Bioavailability of encapsulated resveratrol into nanoemulsion-based delivery systems","volume":"147","author":"Sessa","year":"2014","journal-title":"Food Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2174\/1389201019666180605125234","article-title":"Perspectives of nanoemulsion strategies in the improvement of oral, parenteral and transdermal chemotherapy","volume":"19","author":"Pandey","year":"2018","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ijpharm.2013.10.055","article-title":"Improvement of cellular uptake, In Vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform","volume":"460","author":"Choudhury","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Bahadur, S., Pardhi, D.M., Rautio, J., Rosenholm, J.M., and Pathak, K. (2020). Intranasal nanoemulsions for direct nose-to-brain delivery of actives for CNS disorders. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12121230"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1016\/j.bmc.2017.11.001","article-title":"Nose-to-brain peptide delivery\u2014The potential of nanotechnology","volume":"26","author":"Samaridou","year":"2018","journal-title":"Bioorganic Med. Chem."},{"key":"ref_143","first-page":"2144","article-title":"Incorporation of carbopol to palm olein based analgesic cream: Effect on formulation characteristics","volume":"36","author":"Win","year":"2017","journal-title":"Lat. Am. J. Pharm."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Duong, V.-A., Nguyen, T.-T.-L., and Maeng, H.-J. (2020). Preparation of solid lipid nanoparticles and nanostructured lipid carriers for drug delivery and the effects of preparation parameters of solvent injection method. Molecules, 25.","DOI":"10.3390\/molecules25204781"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Chen, H., Zhang, Y., Yu, T., Song, G., Xu, T., Xin, T., Lin, Y., and Han, B. (2022). Nano-based drug delivery systems for periodontal tissue regeneration. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102250"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1021\/acs.bioconjchem.2c00376","article-title":"Spotlight on photoactivatable liposomes beyond drug delivery: An enabler of multitargeting of molecular pathways","volume":"33","author":"Saad","year":"2022","journal-title":"Bioconjugate Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41401-022-00902-w","article-title":"Current advances in the use of exosomes, liposomes, and bioengineered hybrid nanovesicles in cancer detection and therapy","volume":"43","author":"Mukherjee","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Luiz, M.T., Dutra, J.A.P., Tofani, L.B., de Ara\u00fajo, J.T.C., Di Filippo, L.D., Marchetti, J.M., and Chorilli, M. (2022). Targeted liposomes: A nonviral gene delivery system for cancer therapy. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040821"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1016\/S0169-409X(02)00118-7","article-title":"Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations","volume":"54","author":"Radtke","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Sivadasan, D., Sultan, M.H., Madkhali, O., Almoshari, Y., and Thangavel, N. (2021). Polymeric lipid hybrid nanoparticles (plns) as emerging drug delivery platform\u2014A comprehensive review of their properties, preparation methods, and therapeutic applications. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13081291"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"137","DOI":"10.17480\/psk.2023.67.3.137","article-title":"Lipid-based Liquid Crystalline Phases for Biocompatible and Versatile Drug Delivery","volume":"67","author":"Kim","year":"2023","journal-title":"Yakhak Hoeji"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"123546","DOI":"10.1016\/j.ijpharm.2023.123546","article-title":"Lyotropic liquid crystalline phases: Drug delivery and biomedical applications","volume":"647","author":"Chavda","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s40005-021-00529-9","article-title":"Surface modification strategies for high-dose dry powder inhalers","volume":"51","author":"Park","year":"2021","journal-title":"J. Pharm. Investig."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s40005-022-00565-z","article-title":"Micronization of a poorly water-soluble drug, fenofibrate, via supercritical-fluid-assisted spray-drying","volume":"52","author":"Kim","year":"2022","journal-title":"J. Pharm. Investig."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s13346-012-0108-9","article-title":"Nasal drug delivery devices: Characteristics and performance in a clinical perspective\u2014A review","volume":"3","author":"Djupesland","year":"2013","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"81","DOI":"10.4103\/2231-4040.82950","article-title":"Nanosuspension: An approach to enhance solubility of drugs","volume":"2","author":"Patel","year":"2011","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_157","first-page":"8","article-title":"An overview: Microspheres as a nasal drug delivery system","volume":"5","author":"Chaudhari","year":"2010","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Adepu, S., and Ramakrishna, S. (2021). Controlled drug delivery systems: Current status and future directions. Molecules, 26.","DOI":"10.3390\/molecules26195905"},{"key":"ref_159","unstructured":"Kulkarni, V.S., and Shaw, C. (2015). Essential Chemistry for Formulators of Semisolid and Liquid Dosages, Academic Press."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"119064","DOI":"10.1016\/j.molliq.2022.119064","article-title":"Measurement and correlation of solubility of rivaroxaban in dichloromethane and primary alcohol binary solvent mixtures at different temperatures","volume":"357","author":"Jeong","year":"2022","journal-title":"J. Mol. Liq."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Aderibigbe, B.A. (2018). In situ-based gels for nose to brain delivery for the treatment of neurological diseases. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020040"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"106294","DOI":"10.1016\/j.ejps.2022.106294","article-title":"Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin","volume":"179","author":"Corazza","year":"2022","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s40005-020-00505-9","article-title":"Thermosensitive nasal in situ gelling systems of rufinamide formulated using modified tamarind seed xyloglucan for direct nose-to-brain delivery: Design, physical characterization, and In Vivo evaluation","volume":"51","author":"Dalvi","year":"2021","journal-title":"J. Pharm. Investig."},{"key":"ref_164","first-page":"1322","article-title":"Advantageous nasal drug delivery system: A review","volume":"2","author":"Chhajed","year":"2011","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"111781","DOI":"10.1016\/j.colsurfb.2021.111781","article-title":"Strategies of confining green tea catechin compounds in nano-biopolymeric matrices: A review","volume":"204","author":"Sabaghi","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Aderibigbe, B.A., and Naki, T. (2018). Design and efficacy of nanogels formulations for intranasal administration. Molecules, 23.","DOI":"10.3390\/molecules23061241"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jconrel.2017.11.040","article-title":"Nose-to-brain delivery of insulin enhanced by a nanogel carrier","volume":"270","author":"Picone","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"954470","DOI":"10.3389\/fbioe.2022.954470","article-title":"Nanogels as novel nanocarrier systems for efficient delivery of CNS therapeutics","volume":"10","author":"Zhang","year":"2022","journal-title":"Front. Bioeng. Biotechnol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/8\/958\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:15:30Z","timestamp":1760033730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/8\/958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":168,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["pharmaceutics17080958"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17080958","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,24]]}}}