<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Current Pharmaceutical Design</journal-id><journal-title-group><journal-title xml:lang="en">Current Pharmaceutical Design</journal-title><trans-title-group xml:lang="ru"><trans-title>Current Pharmaceutical Design</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1381-6128</issn><issn publication-format="electronic">1873-4286</issn><publisher><publisher-name xml:lang="en">Bentham Science</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">645916</article-id><article-id pub-id-type="doi">10.2174/0113816128317347240625105501</article-id><article-categories><subj-group subj-group-type="toc-heading"><subject>Immunology, Inflammation &amp;amp; Allergy</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Key Challenges, Influencing Factors, and Future Perspectives of Nanosuspensions in Enhancing Brain Drug Delivery</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Wenlu</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Chongzhao</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name><surname>Xue</surname><given-names>Linying</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Yancai</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff id="aff1"><institution>School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences)</institution></aff><aff id="aff2"><institution>School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology (Shandong Academy of Sciences)</institution></aff><aff id="aff3"><institution>School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences),</institution></aff><pub-date date-type="pub" iso-8601-date="2024-08-30" publication-format="electronic"><day>30</day><month>08</month><year>2024</year></pub-date><volume>30</volume><issue>32</issue><issue-title xml:lang="ru"/><fpage>2524</fpage><lpage>2537</lpage><history><date date-type="received" iso-8601-date="2025-01-11"><day>11</day><month>01</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Bentham Science Publishers</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Bentham Science Publishers</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://journals.eco-vector.com/1381-6128/article/view/645916">https://journals.eco-vector.com/1381-6128/article/view/645916</self-uri><abstract xml:lang="en"><p>Many brain diseases pose serious challenges to human life. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common neurodegenerative diseases that seriously threaten human health. Glioma is a common malignant tumor. However, drugs cannot cross physiological and pathological barriers and most therapeutic drugs cannot enter the brain because of the presence of the Blood-brain Barrier (BBB) and Bloodbrain Tumor Barrier (BBTB). How to enable drugs to penetrate the BBB to enter the brain, reduce systemic toxicity, and penetrate BBTB to exert therapeutic effects has become a challenge. Nanosuspension can successfully formulate drugs that are difficult to dissolve in water and oil by using surfactants as stabilizers, which is suitable for the brain target delivery of class II and IV drugs in the Biopharmaceutical Classification System (BCS). In nanosuspension drug delivery systems, the physical properties of nanostructures have a great impact on the accumulation of drugs at the target site, such as the brain. Optimizing the physical parameters of the nanosuspension can improve the efficiency of brain drug delivery and disease treatment. Therefore, the key challenges, influencing factors, and future perspectives of nanosuspension in enhancing brain drug delivery are summarized and reviewed here. This article aims to provide a better understanding of nanosuspension formulation technology used for brain delivery and strategies used to overcome various physiological barriers.</p></abstract><kwd-group xml:lang="en"><kwd>Nanosuspension</kwd><kwd>nanocrystals</kwd><kwd>brain target</kwd><kwd>nasal drug delivery</kwd><kwd>blood-brain barrier</kwd><kwd>brain diseases.</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Liu J, Qu S, Wang T, et al. Nanosuspensions as an approach for improved solubility and anti-Ichthyophthirius multifiliis activity of magnolol. Aquaculture 2024; 579: 740133. doi: 10.1016/j.aquaculture.2023.740133</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Ma L, Gao H, Cheng C, Cao M, Zou L, Liu W. Fabrication of emulsions using high loaded curcumin nanosuspension stabilizers: Enhancement of antioxidant activity and concentration of curcumin in micelles. J Funct Foods 2023; 110: 105858. doi: 10.1016/j.jff.2023.105858</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Patel D, Zode SS, Bansal AK. Formulation aspects of intravenous nanosuspensions. Int J Pharm 2020; 586: 119555. doi: 10.1016/j.ijpharm.2020.119555 PMID: 32562654</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Xie L, Cai C, Cao Y, Li X. Tea saponins as novel stabilizers for the development of diosmin nanosuspensions: Optimization and in vitro evaluation. J Drug Deliv Sci Technol 2023; 90: 105118. doi: 10.1016/j.jddst.2023.105118</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Boscolo O, Flor S, Salvo L, et al. Formulation and characterization of ursodeoxycholic acid nanosuspension based on bottom-up technology and boxbehnken design optimization. Pharmaceutics 2023; 15(8): 2037. doi: 10.3390/pharmaceutics15082037 PMID: 37631251</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Karakucuk A, Teksin ZS, Eroglu H, Celebi N. Evaluation of improved oral bioavailability of ritonavir nanosuspension. Eur J Pharm Sci 2019; 131: 153-8. doi: 10.1016/j.ejps.2019.02.028 PMID: 30790704</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Wang N, Qi F, He X, et al. Preparation and pharmacokinetic characterization of an anti-virulence compound nanosuspensions. Pharmaceutics 2021; 13(10): 1586. doi: 10.3390/pharmaceutics13101586 PMID: 34683879</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Banarase NB, Kaur CD. Whole whey stabilized oleanolic acid nanosuspension: Formulation and evaluation study. J Drug Deliv Sci Technol 2022; 67: 103001. doi: 10.1016/j.jddst.2021.103001</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Kumar R, Thakur AK, Chaudhari P, et al. Nanoparticle preparation of pharmaceutical compounds via wet milling: Current status and future prospects. Powder Technol 2024; 435: 119430. doi: 10.1016/j.powtec.2024.119430</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Lv Y, Li W, Liao W, et al. Nano-drug delivery systems based on natural products. Int J Nanomed 2024; 19: 541-69. doi: 10.2147/IJN.S443692 PMID: 38260243</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Singhal M, Baumgartner A, Turunen E, van Veen B, Hirvonen J, Peltonen L. Nanosuspensions of a poorly soluble investigational molecule ODM-106: Impact of milling bead diameter and stabilizer concentration. Int J Pharm 2020; 587: 119636. doi: 10.1016/j.ijpharm.2020.119636 PMID: 32659405</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Elbaz NM, Tatham LM, Owen A, Rannard S, McDonald TO. Layer by layer self-assembly for coating a nanosuspension to modify drug release and stability for oral delivery. Food Hydrocoll 2023; 144: 108908. doi: 10.1016/j.foodhyd.2023.108908</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Aguilar-Hernández G, López-Romero BA, Nicolás-García M, Nolasco-González Y, García-Galindo HS, Montalvo-González E. Nanosuspensions as carriers of active ingredients: Chemical composition, development methods, and their biological activities. Food Res Int 2023; 174(Pt 1): 113583. doi: 10.1016/j.foodres.2023.113583 PMID: 37986449</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Fathi-Karkan S, Heidarzadeh M, Narmi MT, et al. Exosome-loaded microneedle patches: Promising factor delivery route. Int J Biol Macromol 2023; 243: 125232. doi: 10.1016/j.ijbiomac.2023.125232 PMID: 37302628</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Abdelhameed AH, Abdelhafez WA, Saleh I, Hamad AA, Mohamed MS. Formulation and optimization of oral fast dissolving films loaded with nanosuspension to enhance the oral bioavailability of Fexofenadine HCL. J Drug Deliv Sci Technol 2023; 85: 104578. doi: 10.1016/j.jddst.2023.104578</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Bhairam M, Pandey RK, Shukla SS, Gidwani B. Preparation, optimization, and evaluation of dolutegravir nanosuspension: In vitro and in vivo characterization. J Pharm Innov 2023; 18(4): 1798-811. doi: 10.1007/s12247-023-09756-z</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Fathi-Karkan S, Amiri Ramsheh N, Arkaban H, et al. Nanosuspensions in ophthalmology: Overcoming challenges and enhancing drug delivery for eye diseases. Int J Pharm 2024; 658: 124226. doi: 10.1016/j.ijpharm.2024.124226 PMID: 38744414</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Fang LR, Wang YH, Xiong ZZ, Wang YM. Research progress of nanomaterials in tumor-targeted drug delivery and imaging therapy. OpenNano 2023; 14: 100184. doi: 10.1016/j.onano.2023.100184</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Gautam S, Lakhanpal I, Sonowal L, Goyal N. Recent advances in targeted drug delivery using metal-organic frameworks: Toxicity and release kinetics. Next Nanotechnol 2023; 3-4: 100027. doi: 10.1016/j.nxnano.2023.100027</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Mustafa G, Hassan D, Zeeshan M, et al. Advances in nanotechnology versus stem cell therapy for the theranostics of Huntingtons disease. J Drug Deliv Sci Technol 2023; 87: 104774. doi: 10.1016/j.jddst.2023.104774</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Wu DD, Salah YA, Ngowi EE, et al. Nanotechnology prospects in brain therapeutics concerning gene-targeting and nose-to-brain administration. iScience 2023; 26(8): 107321. doi: 10.1016/j.isci.2023.107321 PMID: 37554468</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Fan Y, Cui Y, Hao W, et al. Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma. Bioact Mater 2021; 6(12): 4402-14. doi: 10.1016/j.bioactmat.2021.04.027 PMID: 33997516</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Huang L, Huang XH, Yang X, et al. Novel nano-drug delivery system for natural products and their application. Pharmacol Res 2024; 201: 107100. doi: 10.1016/j.phrs.2024.107100 PMID: 38341055</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Niić Nodilo L, Perkuić M, Ugrina I, et al. In situ gelling nanosuspension as an advanced platform for fluticasone propionate nasal delivery. Eur J Pharm Biopharm 2022; 175: 27-42. doi: 10.1016/j.ejpb.2022.04.009 PMID: 35489667</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Leal FC, Ueda KM, Tucunduva Arantes MS, et al. Impact of defibrillation technique on the rheological, thermo-mechanical, and nutritional properties of nanosuspensions produced from multiple fractions of pinhão seed (Araucaria angustifolia (Bertol.) Kuntze). Food Chem 2024; 440: 138195. doi: 10.1016/j.foodchem.2023.138195 PMID: 38103506</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Pourmadadi M, Gerami SE, Ajalli N, et al. Novel pH-responsive hybrid hydrogels for controlled delivery of curcumin: Overcoming conventional constraints and enhancing cytotoxicity in MCF-7 cells. Hybrid Advances 2024; 6: 100210. doi: 10.1016/j.hybadv.2024.100210</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Huang H, Lang Y, Wang S, Zhou M. Microalgae-based drug delivery systems in biomedical applications. Eng Regener 2024. doi: 10.1016/j.engreg.2024.01.002</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Srivastav AK, Karpathak S, Rai MK, Kumar D, Misra DP, Agarwal V. Lipid based drug delivery systems for oral, transdermal and parenteral delivery: Recent strategies for targeted delivery consistent with different clinical application. J Drug Deliv Sci Technol 2023; 85: 104526. doi: 10.1016/j.jddst.2023.104526</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Pourmadadi M, Ostovar S, Ruiz-Pulido G, et al. Novel epirubicin-loaded nanoformulations: Advancements in polymeric nanocarriers for efficient targeted cellular and subcellular anticancer drug delivery. Inorg Chem Commun 2023; 155: 110999. doi: 10.1016/j.inoche.2023.110999</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Aghrbi I, Fülöp V, Jakab G, Kállai-Szabó N, Balogh E, Antal I. Nanosuspension with improved saturated solubility and dissolution rate of cilostazol and effect of solidification on stability. J Drug Deliv Sci Technol 2021; 61: 102165. doi: 10.1016/j.jddst.2020.102165</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Mishra A, Kumar R, Mishra J, et al. Strategies facilitating the permeation of nanoparticles through blood-brain barrier: An insight towards the development of brain-targeted drug delivery system. J Drug Deliv Sci Technol 2023; 86: 104694. doi: 10.1016/j.jddst.2023.104694</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Han L, Jiang C. Evolution of bloodbrain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies. Acta Pharm Sin B 2021; 11(8): 2306-25. doi: 10.1016/j.apsb.2020.11.023 PMID: 34522589</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Li Q, Tang Z, Zhang Y, et al. Application of low-intensity ultrasound by opening bloodbrain barrier for enhanced brain-targeted drug delivery. Int J Pharm 2023; 642: 123191. doi: 10.1016/j.ijpharm.2023.123191 PMID: 37391108</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Liu P, Jiang C. Brain-targeting drug delivery systems. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2022; 14(5): e1818. doi: 10.1002/wnan.1818 PMID: 35596258</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Sethi B, Kumar V, Mahato K, Coulter DW, Mahato RI. Recent advances in drug delivery and targeting to the brain. J Control Release 2022; 350: 668-87. doi: 10.1016/j.jconrel.2022.08.051 PMID: 36057395</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Satapathy BS, Kumar LA, Pattnaik G, Swapna S, Mohanty D. Targeting to brain tumor: Nanocarrier-based drug delivery platforms, opportunities, and challenges. J Pharm Bioallied Sci 2021; 13(2): 172-7. doi: 10.4103/jpbs.JPBS_239_20 PMID: 34349476</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Lan G, Song Q, Luan Y, Cheng Y. Targeted strategies to deliver boron agents across the bloodbrain barrier for neutron capture therapy of brain tumors. Int J Pharm 2024; 650: 123747. doi: 10.1016/j.ijpharm.2023.123747 PMID: 38151104</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Wang P, Wang Y, Li P, et al. Oral delivery of polyester nanoparticles for brain-targeting: Challenges and opportunities. Chin Chem Lett 2023; 34(4): 107691. doi: 10.1016/j.cclet.2022.07.034</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Elbaz NM, Tatham LM, Owen A, Rannard S, McDonald TO. Redispersible nanosuspensions as a plausible oral delivery system for curcumin. Food Hydrocoll 2021; 121: 107005. doi: 10.1016/j.foodhyd.2021.107005</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Pirincci Tok Y, Mesut B, Güngör S, et al. Systematic screening study for the selection of proper stabilizers to produce physically stable canagliflozin nanosuspension by wet milling method. Bioengineering 2023; 10(8): 927. doi: 10.3390/bioengineering10080927 PMID: 37627812</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Ma Y, Wang Y, Wang X, Guo J, Yan B, Guan W. Development and solidification of   multifunction   stabilizers   formulated selfassembled core-shell Deacetyl mycoepoxydience nanosuspensions. J Mol Liq 2020; 312: 113480. doi: 10.1016/j.molliq.2020.113480</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Santos AM, Meneguin AB, Fonseca-Santos B, et al. The role of stabilizers and mechanical processes on physico-chemical and anti-inflammatory properties of methotrexate nanosuspensions. J Drug Deliv Sci Technol 2020; 57: 101638. doi: 10.1016/j.jddst.2020.101638</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Guan W, Ma Y, Ding S, et al. The technology for improving stability of nanosuspensions in drug delivery. J Nanopart Res 2022; 24(1): 14. doi: 10.1007/s11051-022-05403-9</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Vardaka E, Ouranidis A, Nikolakakis I, Kachrimanis K. Development of agomelatine nanocomposite formulations by wet media milling. Eur J Pharm Sci 2021; 166: 105979. doi: 10.1016/j.ejps.2021.105979 PMID: 34425232</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Ouranidis A, Gkampelis N, Vardaka E, et al. Overcoming the solubility barrier of ibuprofen by the rational process design of a nanocrystal formulation. Pharmaceutics 2020; 12(10): 969. doi: 10.3390/pharmaceutics12100969 PMID: 33066680</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Porwal O. Box-Behnken design-based formulation optimization and characterization of spray dried rutin loaded nanosuspension: State of the art. S Afr J Bot 2022; 149: 807-15. doi: 10.1016/j.sajb.2022.04.028</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Li Q, Chen F, Liu Y, et al. A novel albumin wrapped nanosuspension of meloxicam to improve inflammation-targeting effects. Int J Nanomed 2018; 13: 4711-25. doi: 10.2147/IJN.S160714 PMID: 30154656</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Taheri M, Maaref S, Kantzas A, Bryant S, Trudel S. Improving the colloidal stability of PEGylated BaTiO3 nanoparticles with surfactants. Chem Phys 2023; 564: 111701. doi: 10.1016/j.chemphys.2022.111701</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Elmowafy M, Shalaby K, Al-Sanea MM, et al. Influence of stabilizer on the development of luteolin nanosuspension for cutaneous delivery: An in vitro and in vivo evaluation. Pharmaceutics 2021; 13(11): 1812. doi: 10.3390/pharmaceutics13111812 PMID: 34834227</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Cesur S. Combination techniques towards novel drug delivery systems manufacturing: 3D PCL scaffolds enriched with tetracycline-loaded PVP nanoparticles. Eur J Pharm Biopharm 2024; 194: 36-48. doi: 10.1016/j.ejpb.2023.11.022 PMID: 38036066</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Ao H, Li Y, Li H, et al. Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer. Drug Deliv 2020; 27(1): 816-24. doi: 10.1080/10717544.2020.1770372 PMID: 32489130</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Park JS, Choi JH, Joung MY, et al. Design of high-payload ascorbyl palmitate nanosuspensions for enhanced skin delivery. Pharmaceutics 2024; 16(2): 171. doi: 10.3390/pharmaceutics16020171 PMID: 38399233</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Shahidulla SM, Miskan R, Sultana S. Nanosuspensions in pharmaceutical sciences: A comprehensive review. Int J Health Sci Res 2023; 13(7): 332-42. doi: 10.52403/ijhsr.20230745</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Aye KC, Rojanarata T, Ngawhirunpat T, Opanasopit P, Pornpitchanarong C, Patrojanasophon P. Development and optimization of curcumin-nanosuspensions with improved wound healing effect. J Drug Deliv Sci Technol 2023; 89: 104997. doi: 10.1016/j.jddst.2023.104997</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Suo Z, Sun Q, Peng X, et al. Lentinan as a natural stabilizer with bioactivities for preparation of drug: Drug nanosuspensions. Int J Biol Macromol 2021; 184: 101-8. doi: 10.1016/j.ijbiomac.2021.06.056 PMID: 34119545</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Chen H, Deng M, Xie L, Liu K, Zhang X, Li X. Preparation and characterization of quercetin nanosuspensions using gypenosides as novel stabilizers. J Drug Deliv Sci Technol 2022; 67: 102962. doi: 10.1016/j.jddst.2021.102962</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Soroushnia A, Ganji F, Vasheghani-Farahani E, Mobedi H. Effect of combined stabilizers on midazolam nanosuspension properties. Iran Polym J 2022; 31(2): 215-22. doi: 10.1007/s13726-021-00981-2</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Singh MK, Pooja D, Ravuri HG, Gunukula A, Kulhari H, Sistla R. Fabrication of surfactant-stabilized nanosuspension of naringenin to surpass its poor physiochemical properties and low oral bioavailability. Phytomedicine 2018; 40: 48-54. doi: 10.1016/j.phymed.2017.12.021 PMID: 29496174</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Shariare MH, Sharmin S, Jahan I, Reza HM, Mohsin K. The impact of process parameters on carrier free paracetamol nanosuspension prepared using different stabilizers by antisolvent precipitation method. J Drug Deliv Sci Technol 2018; 43: 122-8. doi: 10.1016/j.jddst.2017.10.001</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Al Ashmawy AZG, Eissa NG, El Nahas HM, Balata GF. Fast disintegrating tablet of doxazosin mesylate nanosuspension: Preparation and characterization. J Drug Deliv Sci Technol 2021; 61: 102210. doi: 10.1016/j.jddst.2020.102210</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Bujňáková Z, Kello M, Kováč J, et al. Preparation of As4S4/Fe3O4 nanosuspensions and in-vitro verification of their anticancer activity. Mater Sci Eng C 2020; 110: 110683. doi: 10.1016/j.msec.2020.110683 PMID: 32204110</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Singh Y, Meher JG, Raval K, et al. Nanoemulsion: Concepts, development and applications in drug delivery. J Control Release 2017; 252: 28-49. doi: 10.1016/j.jconrel.2017.03.008 PMID: 28279798</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Wang P, Cao X, Chu Y, Wang P. Ginkgolides-loaded soybean phospholipid-stabilized nanosuspension with improved storage stability and in vivo bioavailability. Colloids Surf B Biointerfaces 2019; 181: 910-7. doi: 10.1016/j.colsurfb.2019.06.050 PMID: 31382340</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Carrigy NB, Ordoubadi M, Liu Y, et al. Amorphous pullulan trehalose microparticle platform for respiratory delivery. Int J Pharm 2019; 563: 156-68. doi: 10.1016/j.ijpharm.2019.04.004 PMID: 30951858</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Jain D, Thakur PS, Thakore SD, Samal SK, Bansal AK. Impact of differential particle size of fenofibrate nanosuspensions on biopharmaceutical performance using physiologically based absorption modeling in rats. J Drug Deliv Sci Technol 2020; 60: 102040. doi: 10.1016/j.jddst.2020.102040</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Wang R, Wang X, Jia X, Wang H, Li W, Li J. Impacts of particle size on the cytotoxicity, cellular internalization, pharmacokinetics and biodistribution of betulinic acid nanosuspensions in combined chemotherapy. Int J Pharm 2020; 588: 119799. doi: 10.1016/j.ijpharm.2020.119799 PMID: 32828973</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Guo C, Chen Y, Zhu J, et al. Preparation, optimization of intravenous ZL-004 nanosuspensions by the precipitation method, effect of particle size on in vivo pharmacokinetics and tissue distribution. J Drug Deliv Sci Technol 2019; 50: 313-20. doi: 10.1016/j.jddst.2019.01.034</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Suriyaamporn P, Pornpitchanarong C, Pamornpathomkul B, et al. Ganciclovir nanosuspension-loaded detachable microneedles patch for enhanced drug delivery to posterior eye segment. J Drug Deliv Sci Technol 2023; 88: 104975. doi: 10.1016/j.jddst.2023.104975</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Pezik E, Gulsun T, Gündüz MG, Sahin S, Öztürk N, Vural İ. Preparation of nanosuspensions of a 1,4-dihydropyridine-based mixed L-/T-type calcium channel blocker by combined precipitation and ultrasonication methods. J Drug Deliv Sci Technol 2023; 87: 104772. doi: 10.1016/j.jddst.2023.104772</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Kolipaka T, Sen S, Mane SS, Bajad GD, Dengale SJ, Ranjan OP. Development of posaconazole nanosuspension for bioavailability enhancement: Formulation optimization, in vitro characterization, and pharmacokinetic study. J Drug Deliv Sci Technol 2023; 83: 104434. doi: 10.1016/j.jddst.2023.104434</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Qin M, Ye G, Xin J, et al. Comparison of in vivo behaviors of intramuscularly long-acting celecoxib nanosuspensions with different particle sizes for the postoperative pain treatment. Int J Pharm 2023; 636: 122793. doi: 10.1016/j.ijpharm.2023.122793 PMID: 36870401</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Wang Y, Song J, Chow SF, Chow AHL, Zheng Y. Particle size tailoring of ursolic acid nanosuspensions for improved anticancer activity by controlled antisolvent precipitation. Int J Pharm 2015; 494(1): 479-89. doi: 10.1016/j.ijpharm.2015.08.052 PMID: 26302857</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Yao S, Chen N, Sun X, Wang Q, Li M, Chen Y. Size-dependence of the skin penetration of andrographolide nanosuspensions: In vitro release ex vivo permeation correlation and visualization of the delivery pathway. Int J Pharm 2023; 641: 123065. doi: 10.1016/j.ijpharm.2023.123065 PMID: 37225025</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Jung SY, Kim S, Kang Z, et al. Efficiency of a dexamethasone nanosuspension as an intratympanic injection for acute hearing loss. Drug Deliv 2022; 29(1): 149-60. doi: 10.1080/10717544.2021.2021320 PMID: 34967280</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Shaikh MS, Kale MA. Formulation and molecular docking simulation study of luliconazole nanosuspensionbased nanogel for transdermal drug delivery using modified polymer. Mater Today Chem 2020; 18: 100364. doi: 10.1016/j.mtchem.2020.100364</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Liu Y, Ma Y, Xue L, Guan W, Wang Y. Pulmonary multidrug codelivery of curcumin nanosuspensions and ciprofloxacin with N-acetylcysteine for lung infection therapy. J Drug Deliv Sci Technol 2023; 84: 104474. doi: 10.1016/j.jddst.2023.104474</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>Yan R, Xu L, Wang Q, et al. Cyclosporine a nanosuspensions for ophthalmic delivery: A comparative study between cationic nanoparticles and drug-core mucus penetrating nanoparticles. Mol Pharm 2021; 18(12): 4290-8. doi: 10.1021/acs.molpharmaceut.1c00370 PMID: 34731571</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>Park JS, Kim MS, Joung MY, et al. Design of montelukast nanocrystalline suspension for parenteral prolonged delivery. Int J Nanomed 2022; 17: 3673-90. doi: 10.2147/IJN.S375888 PMID: 36046838</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>Sinha B, Staufenbiel S, Müller RH, Möschwitzer JP. Sub-50 nm ultra-small organic drug nanosuspension prepared by cavi-precipitation and its brain targeting potential. Int J Pharm 2021; 607: 120983. doi: 10.1016/j.ijpharm.2021.120983 PMID: 34371150</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>Faujan NH, Abedi Karjiban R, Kashaban I, Basri M, Basri H. Computational simulation of palm kernel oil-based esters nano-emulsions aggregation as a potential parenteral drug delivery system. Arab J Chem 2019; 12(8): 2372-83. doi: 10.1016/j.arabjc.2015.03.003</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>Jiang K, Yu Y, Qiu W, et al. Protein corona on brain targeted nanocarriers: Challenges and prospects. Adv Drug Deliv Rev 2023; 202: 115114. doi: 10.1016/j.addr.2023.115114 PMID: 37827336</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>Chen Y, Zhang C, Huang Y, et al. Intranasal drug delivery: The interaction between nanoparticles and the nose-to-brain pathway. Adv Drug Deliv Rev 2024; 207: 115196. doi: 10.1016/j.addr.2024.115196 PMID: 38336090</mixed-citation></ref><ref id="B83"><label>83.</label><mixed-citation>Raghav M, Gupta V, Awasthi R, Singh A, Kulkarni GT. Noseto-brain drug delivery: Challenges and progress towards brain targeting in the treatment of neurological disorders. J Drug Deliv Sci Technol 2023; 86: 104756. doi: 10.1016/j.jddst.2023.104756</mixed-citation></ref><ref id="B84"><label>84.</label><mixed-citation>Dogra A, Narang RS, Kaur T, Narang JK. Mefenamic acid loaded and TPGS stabilized mucoadhesive nanoemulsion for the treatment of Alzheimers disease: Development, optimization, and brain-targeted delivery via olfactory pathway. AAPS PharmSciTech 2024; 25(1): 16. doi: 10.1208/s12249-023-02727-0 PMID: 38200387</mixed-citation></ref><ref id="B85"><label>85.</label><mixed-citation>Emad NA, Ahmed B, Alhalmi A, Alzobaidi N, Al-Kubati SS. Recent progress in nanocarriers for direct nose to brain drug delivery. J Drug Deliv Sci Technol 2021; 64: 102642. doi: 10.1016/j.jddst.2021.102642</mixed-citation></ref><ref id="B86"><label>86.</label><mixed-citation>Huang Q, Chen Y, Zhang W, et al. Nanotechnology for enhanced nose-to-brain drug delivery in treating neurological diseases. J Control Release 2024; 366: 519-34. doi: 10.1016/j.jconrel.2023.12.054 PMID: 38182059</mixed-citation></ref><ref id="B87"><label>87.</label><mixed-citation>McGuckin MB, Wang J, Ghanma R, et al. Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes. J Control Release 2022; 345: 334-53. doi: 10.1016/j.jconrel.2022.03.012 PMID: 35283257</mixed-citation></ref><ref id="B88"><label>88.</label><mixed-citation>Agrawal M, Saraf S, Saraf S, et al. Stimuli-responsive in situ gelling system for nose-to-brain drug delivery. J Control Release 2020; 327: 235-65. doi: 10.1016/j.jconrel.2020.07.044 PMID: 32739524</mixed-citation></ref><ref id="B89"><label>89.</label><mixed-citation>Pires PC, Santos AO. Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies. J Control Release 2018; 270: 89-100. doi: 10.1016/j.jconrel.2017.11.047 PMID: 29199063</mixed-citation></ref><ref id="B90"><label>90.</label><mixed-citation>Wen MM, El-Salamouni NS, El-Refaie WM, et al. Nanotechnology-based drug delivery systems for Alzheimers disease management: Technical, industrial, and clinical challenges. J Control Release 2017; 245: 95-107. doi: 10.1016/j.jconrel.2016.11.025 PMID: 27889394</mixed-citation></ref><ref id="B91"><label>91.</label><mixed-citation>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. doi: 10.1016/j.apsb.2021.02.012 PMID: 33996407</mixed-citation></ref><ref id="B92"><label>92.</label><mixed-citation>Long Y, Yang Q, Xiang Y, et al. Nose to brain drug delivery: A promising strategy for active components from herbal medicine for treating cerebral ischemia reperfusion. Pharmacol Res 2020; 159: 104795. doi: 10.1016/j.phrs.2020.104795 PMID: 32278035</mixed-citation></ref><ref id="B93"><label>93.</label><mixed-citation>Antimisiaris SG, Marazioti A, Kannavou M, et al. Overcoming barriers by local drug delivery with liposomes. Adv Drug Deliv Rev 2021; 174: 53-86. doi: 10.1016/j.addr.2021.01.019 PMID: 33539852</mixed-citation></ref><ref id="B94"><label>94.</label><mixed-citation>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. doi: 10.1016/j.jddst.2021.102533</mixed-citation></ref><ref id="B95"><label>95.</label><mixed-citation>Huang G, Xie J, Shuai S, et al. Nose-to-brain delivery of drug nanocrystals by using Ca2+ responsive deacetylated gellan gum based in situ nanogel. Int J Pharm 2021; 594: 120182. doi: 10.1016/j.ijpharm.2020.120182 PMID: 33346126</mixed-citation></ref><ref id="B96"><label>96.</label><mixed-citation>Hang L, Shen C, Shen B, Yuan H. Insight into the in vivo fate of intravenous herpetrione amorphous nanosuspensions by aggregation-caused quenching probes. Chin Chem Lett 2022; 33(11): 4948-51. doi: 10.1016/j.cclet.2022.03.108</mixed-citation></ref><ref id="B97"><label>97.</label><mixed-citation>Pınar SG, Canpınar H, Tan Ç, Çelebi N. A new nanosuspension prepared with wet milling method for oral delivery of highly variable drug Cyclosporine A: Development, optimization and in vivo evaluation. Eur J Pharm Sci 2022; 171: 106123. doi: 10.1016/j.ejps.2022.106123 PMID: 35017012</mixed-citation></ref><ref id="B98"><label>98.</label><mixed-citation>Luo M, Sun H, Jiang Q, et al. Novel nanocrystal injection of insoluble drug anlotinib and its antitumor effects on hepatocellular carcinoma. Front Oncol 2021; 11: 777356. doi: 10.3389/fonc.2021.777356 PMID: 34926286</mixed-citation></ref><ref id="B99"><label>99.</label><mixed-citation>Chavda VP, Dawre S, Pandya A, et al. Lyotropic liquid crystals for parenteral drug delivery. J Control Release 2022; 349: 533-49. doi: 10.1016/j.jconrel.2022.06.062 PMID: 35792188</mixed-citation></ref><ref id="B100"><label>100.</label><mixed-citation>Kumar V, Gupta U. Tailor-made nanocargoes as promising tool for brain targeting: Modulated approaches with better therapeutic outcomes. J Drug Deliv Sci Technol 2023; 84: 104466. doi: 10.1016/j.jddst.2023.104466</mixed-citation></ref><ref id="B101"><label>101.</label><mixed-citation>Shah S, Patel AA, Pandya V, et al. Breaking barriers: Intranasal delivery of brexpiprazole-nanostructured lipid carriers targets the brain for effective schizophrenia treatment. J Drug Deliv Sci Technol 2023; 90: 105160. doi: 10.1016/j.jddst.2023.105160</mixed-citation></ref><ref id="B102"><label>102.</label><mixed-citation>Pınar SG, Oktay AN, Karaküçük AE, Çelebi N. Formulation strategies of nanosuspensions for various administration routes. Pharmaceutics 2023; 15(5): 1520. doi: 10.3390/pharmaceutics15051520 PMID: 37242763</mixed-citation></ref><ref id="B103"><label>103.</label><mixed-citation>Aldeeb M, Wilar G, Suhandi C, Elamin K, Wathoni N. Nanosuspension-based drug delivery systems for topical applications. Int J Nanomed 2024; 19: 825-44. doi: 10.2147/IJN.S447429 PMID: 38293608</mixed-citation></ref></ref-list></back></article>
