{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T04:10:36Z","timestamp":1785039036557,"version":"3.55.0"},"reference-count":112,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"faculty seed grant (FSG), NJIT"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Traumatic brain injury (TBI) is a major source of death and disability worldwide as a result of motor vehicle accidents, falls, attacks and bomb explosions. Currently, there are no FDA-approved drugs to treat TBI patients predominantly because of a lack of appropriate methods to deliver drugs to the brain for therapeutic effect. Existing clinical and pre-clinical studies have shown that minocycline\u2019s neuroprotective effects either through high plasma protein binding or an increased dosage requirement have resulted in neurotoxicity. In this study, we focus on the formulation, characterization, in vivo biodistribution, behavioral improvements, neuroprotective effect and toxicity of transferrin receptor-targeted (tf) conjugated minocycline loaded albumin nanoparticles in a blast-induced TBI model. A novel tf conjugated minocycline encapsulated albumin nanoparticle was developed, characterized and quantified using a validated HPLC method as well as other various analytical methods. The results of the nanoformulation showed small, narrow hydrodynamic size distributions, with high entrapment, loading efficiencies and sustained release profiles. Furthermore, the nanoparticle administered at minimal doses in a rat model of blast TBI was able to cross the blood\u2013brain barrier, enhanced nanoparticle accumulation in the brain, improved behavioral outcomes, neuroprotection, and reduced toxicity compared to free minocycline. Hence, tf conjugated minocycline loaded nanoparticle elicits a neuroprotective effect and can thus offer a potential therapeutic effect.<\/jats:p>","DOI":"10.3390\/brainsci13030402","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:22:16Z","timestamp":1677464536000},"page":"402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5279-8964","authenticated-orcid":false,"given":"Venkatesan","family":"Perumal","sequence":"first","affiliation":[{"name":"Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2711-6236","authenticated-orcid":false,"given":"Arun Reddy","family":"Ravula","sequence":"additional","affiliation":[{"name":"Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8564-3168","authenticated-orcid":false,"given":"Agnieszka","family":"Agas","sequence":"additional","affiliation":[{"name":"Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakaash","family":"Gosain","sequence":"additional","affiliation":[{"name":"Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aswati","family":"Aravind","sequence":"additional","affiliation":[{"name":"Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ponnurengam Malliappan","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Institute of Research and Development, Duy Tan University, Da Nang 550000, Vietnam"},{"name":"School of Medicine and Pharmacy, Duy Tan University, Da Nang 550000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanmuga Sundari","family":"I","sequence":"additional","affiliation":[{"name":"Computational Biology Special Lab, Department of Biotechnology, Bannari Amman Institute of Technology, Sathyamangalam 638401, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-7167","authenticated-orcid":false,"given":"Karthik","family":"Sambath","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Environmental Science, College of Science and Liberal Arts, New Jersey Institute of Technology, 323 Martin Luther King Jr. Blvd., Newark, NJ 07102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-6716","authenticated-orcid":false,"given":"Sivakumar","family":"Vijayaraghavalu","sequence":"additional","affiliation":[{"name":"Department of Life Sciences (Zoology), Manipur University, Imphal 795003, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namas","family":"Chandra","sequence":"additional","affiliation":[{"name":"Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1089\/neu.2012.2399","article-title":"Repeated mild traumatic brain injury: Mechanisms of cerebral vulnerability","volume":"30","author":"Prins","year":"2013","journal-title":"J. Neurotrauma"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cjtee.2018.02.003","article-title":"Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities","volume":"21","author":"Xiong","year":"2018","journal-title":"Chin. J. Traumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1093\/brain\/awv139","article-title":"Military Blast Exposure, Ageing and White Matter Integrity","volume":"138","author":"Trotter","year":"2015","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/ACO.0b013e32834458da","article-title":"Traumatic Brain Injury in Modern War","volume":"24","author":"Ling","year":"2011","journal-title":"Curr. Opin. Anesthesiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.jemermed.2015.03.013","article-title":"Blast Injuries","volume":"49","author":"Mathews","year":"2015","journal-title":"J. Emerg. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Moore, B. (2015). Blast Injuries-a Prehospital Perspective. Australas. J. Paramed., 4.","DOI":"10.33151\/ajp.4.1.359"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"221101","DOI":"10.1103\/PhysRevLett.116.221101","article-title":"Tests of General Relativity with GW150914","volume":"116","author":"Abbott","year":"2016","journal-title":"Phys. Rev. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.tips.2010.09.005","article-title":"Neuroprotection for traumatic brain injury: Translational challenges and emerging therapeutic strategies","volume":"31","author":"Loane","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.nurt.2009.10.022","article-title":"Clinical trials in traumatic brain injury: Past experience and current developments","volume":"7","author":"Maas","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3389\/fneur.2012.00111","article-title":"Acute minocycline treatment mitigates the symptoms of mild blast-induced traumatic brain injury","volume":"3","author":"Kovesdi","year":"2012","journal-title":"Front. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.nano.2016.10.004","article-title":"Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy","volume":"13","author":"Brenza","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1002\/jbm.a.36477","article-title":"Biodegradable polyanhydride-based nanomedicines for blood to brain drug delivery","volume":"106","author":"Brenza","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1352\/1944-7558-115.5.433","article-title":"Side effects of minocycline treatment in patients with fragile X syndrome and exploration of outcome measures","volume":"115","author":"Utari","year":"2010","journal-title":"Am. J. Intellect. Dev. Disabil."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1365-2125.2011.03991.x","article-title":"Neurotoxic effects associated with antibiotic use: Management considerations","volume":"72","author":"Grill","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0378-4347(97)00647-6","article-title":"Analysis of minocycline by high-performance liquid chromatography in tissue and serum","volume":"706","author":"Wrightson","year":"1998","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jpba.2019.02.036","article-title":"Development, validation and application of a novel HPLC-MS\/MS method for the measurement of minocycline in human plasma and urine","volume":"169","author":"Bayliss","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bph.12139","article-title":"Minocycline: Far beyond an antibiotic","volume":"169","author":"Zarzuelo","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1592\/phco.26.4.515","article-title":"Minocycline for short-term neuroprotection","volume":"26","author":"Elewa","year":"2006","journal-title":"Pharmacotherapy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"212553","DOI":"10.7573\/dic.212553","article-title":"The therapeutic role of minocycline in Parkinson\u2019s disease","volume":"8","author":"Cankaya","year":"2019","journal-title":"Drugs Context"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e10248","DOI":"10.15252\/emmm.201810248","article-title":"Inflammasomes in neuroinflammatory and neurodegenerative diseases","volume":"11","author":"Voet","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3389\/fncel.2018.00323","article-title":"Bidirectional Microglia\u2013Neuron Communication in Health and Disease","volume":"12","author":"Szepesi","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.neuroscience.2015.07.051","article-title":"Minocycline ameliorates hypoxia-induced blood-brain barrier damage by inhibition of HIF-1alpha through SIRT-3\/PHD-2 degradation pathway","volume":"304","author":"Yang","year":"2015","journal-title":"Neuroscience"},{"key":"ref_23","first-page":"250","article-title":"The blood brain barrier in cerebral ischemic injury\u2014Disruption and repair","volume":"304","author":"Zhang","year":"2020","journal-title":"Brain Hemorrhages"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"C135","DOI":"10.1152\/ajpcell.00136.2018","article-title":"Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke","volume":"316","author":"Yang","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1021\/acs.bioconjchem.7b00569","article-title":"Activated Microglia Targeting Dendrimer-Minocycline Conjugate as Therapeutics for Neuroinflammation","volume":"28","author":"Sharma","year":"2017","journal-title":"Bioconjugate Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1248\/cpb.c12-00732","article-title":"Formulation, Optimization, in Vivo Pharmacokinetic, Behavioral and Biochemical Estimations of Minocycline Loaded Chitosan Nanoparticles for Enhanced Brain Uptake","volume":"61","author":"Nagpal","year":"2013","journal-title":"Chem. Pharm. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1523\/JNEUROSCI.5275-03.2004","article-title":"Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury","volume":"24","author":"Stirling","year":"2004","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.clinthera.2005.09.005","article-title":"Safety of doxycycline and minocycline: A systematic review","volume":"27","author":"Smith","year":"2005","journal-title":"Clin. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jgar.2020.01.022","article-title":"Minocycline, Focused on mechanisms of resistance, antibacterial activity, and clinical effectiveness; Back to Future","volume":"22","author":"Asadi","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_30","first-page":"674","article-title":"Synthesis and characterisation of ultrasound imageable heat-sensitive liposomes for HIFU therapy","volume":"31","author":"Maples","year":"2015","journal-title":"Int. J. Hyperth."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s12645-011-0017-5","article-title":"Effect of liposomal celecoxib on proliferation of colon cancer cell and inhibition of DMBA-induced tumor in rat model","volume":"2","author":"Perumal","year":"2011","journal-title":"Cancer Nanotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104908","DOI":"10.1016\/j.micpath.2021.104908","article-title":"Nanotechnology-based approaches for emerging and re-emerging viruses: Special emphasis on COVID-19","volume":"156","author":"Saravanan","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8681","DOI":"10.1038\/s41598-018-26813-7","article-title":"Temporal and Spatial Effects of Blast Overpressure on Blood-Brain Barrier Permeability in Traumatic Brain Injury","volume":"8","author":"Kuriakose","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1089\/neu.2017.5358","article-title":"A Single Primary Blast-Induced Traumatic Brain Injury in a Rodent Model Causes Cell-Type Dependent Increase in Nicotinamide Adenine Dinucleotide Phosphate Oxidase Isoforms in Vulnerable Brain Regions","volume":"35","author":"Rao","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1074\/jbc.M115.690941","article-title":"Transferrin Receptor 1 Facilitates Poliovirus Permeation of Mouse Brain Capillary Endothelial Cells","volume":"291","author":"Mizutani","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10396","DOI":"10.1038\/s41598-017-11220-1","article-title":"Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma","volume":"7","author":"Johnsen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1124\/jpet.105.097139","article-title":"Covalent linkage of apolipoprotein e to albumin nanoparticles strongly enhances drug transport into the brain","volume":"317","author":"Michaelis","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jconrel.2009.03.002","article-title":"Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones","volume":"137","author":"Zensi","year":"2009","journal-title":"J. Control. Release"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ejpb.2008.08.021","article-title":"Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood-brain barrier (BBB)","volume":"71","author":"Ulbrich","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9999","DOI":"10.1021\/acsnano.6b04268","article-title":"Blood\u2013Brain-Barrier-Penetrating Albumin Nanoparticles for Biomimetic Drug Delivery via Albumin-Binding Protein Pathways for Antiglioma Therapy","volume":"10","author":"Lin","year":"2016","journal-title":"ACS Nano"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.apsb.2016.05.013","article-title":"Progress and perspectives on targeting nanoparticles for brain drug delivery","volume":"6","author":"Gao","year":"2016","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.2147\/IJN.S61288","article-title":"Current approaches to enhance CNS delivery of drugs across the brain barriers","volume":"9","author":"Lu","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/neuonc\/not016","article-title":"Which drug or drug delivery system can change clinical practice for brain tumor therapy?","volume":"15","author":"Siegal","year":"2013","journal-title":"Neuro-Oncology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.7150\/thno.19365","article-title":"Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery","volume":"7","author":"An","year":"2017","journal-title":"Theranostics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fchem.2014.00049","article-title":"Nanoparticles from renewable polymers","volume":"2","author":"Wurm","year":"2014","journal-title":"Front. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"321","DOI":"10.4161\/hv.26796","article-title":"Polymeric nanoparticles: Potent vectors for vaccine delivery targeting cancer and infectious diseases","volume":"10","author":"Bolhassani","year":"2014","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"111630","DOI":"10.1016\/j.jphotobiol.2019.111630","article-title":"Near infra-red polymeric nanoparticle based optical imaging in Cancer diagnosis","volume":"199","author":"Perumal","year":"2019","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.apsb.2017.11.005","article-title":"Biomacromolecules as carriers in drug delivery and tissue engineering","volume":"8","author":"Zhang","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.3390\/ijms14011629","article-title":"Biopolymer-based nanoparticles for drug\/gene delivery and tissue engineering","volume":"14","author":"Nitta","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cocis.2014.07.002","article-title":"Biopolymer-based nanoparticles and microparticles: Fabrication, characterization, and application","volume":"19","author":"Joye","year":"2014","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.biopha.2017.11.026","article-title":"Nanotherapeutics: An insight into healthcare and multi-dimensional applications in medical sector of the modern world","volume":"97","author":"Prasad","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s40005-016-0250-3","article-title":"Albumin-based potential drugs: Focus on half-life extension and nanoparticle preparation","volume":"46","author":"Lee","year":"2016","journal-title":"J. Pharm. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1111\/jphp.12460","article-title":"Development of glutathione-conjugated asiatic acid-loaded bovine serum albumin nanoparticles for brain-targeted drug delivery","volume":"67","author":"Raval","year":"2015","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13058-015-0587-y","article-title":"nab-Paclitaxel dose and schedule in breast cancer","volume":"17","year":"2015","journal-title":"Breast Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1158\/1535-7163.MCT-15-0104","article-title":"Selective Nuclear Export Inhibitor KPT-330 Enhances the Antitumor Activity of Gemcitabine in Human Pancreatic Cancer","volume":"14","author":"Kazim","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0928-0987(00)00166-4","article-title":"Drug targeting","volume":"11","author":"Torchilin","year":"2000","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1038\/aps.2009.125","article-title":"Preparation of albumin nanospheres loaded with gemcitabine and their cytotoxicity against BXPC-3 cells in vitro","volume":"30","author":"Li","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s41048-018-0079-6","article-title":"Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells","volume":"5","author":"Motevalli","year":"2019","journal-title":"Biophys. Rep."},{"key":"ref_59","first-page":"695","article-title":"An In-vitro Investigation of Swelling Controlled Delivery of Insulin from Egg Albumin Nanocarriers","volume":"15","author":"Mahobia","year":"2016","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/NSA.S117018","article-title":"Synthetic nanoparticles of bovine serum albumin with entrapped salicylic acid","volume":"10","author":"Costa","year":"2016","journal-title":"Nanotechnol. Sci. Appl."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7717","DOI":"10.1038\/s41598-019-44147-w","article-title":"Synergistic Role of Oxidative Stress and Blood-Brain Barrier Permeability as Injury Mechanisms in the Acute Pathophysiology of Blast-induced Neurotrauma","volume":"9","author":"Kuriakose","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_62","first-page":"9285854","article-title":"Protein Based Nanostructures for Drug Delivery","volume":"2018","author":"Verma","year":"2018","journal-title":"J. Pharm"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/1556-276X-8-176","article-title":"Gemcitabine-loaded albumin nanospheres (GEM-ANPs) inhibit PANC-1 cells in vitro and in vivo","volume":"8","author":"Li","year":"2013","journal-title":"Nanoscale Res. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1208\/s12249-010-9519-4","article-title":"Modified nanoprecipitation method for preparation of cytarabine-loaded PLGA nanoparticles","volume":"11","author":"Yadav","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"368","DOI":"10.18433\/J3H88D","article-title":"Pharmacokinetics and biodistribution of human serum albumin-TIMP-2 fusion protein using near-infrared optical imaging","volume":"14","author":"Lee","year":"2011","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1080\/21691401.2018.1548468","article-title":"Folate-conjugated human serum albumin-encapsulated resveratrol nanoparticles: Preparation, characterization, bioavailability and targeting of liver tumors","volume":"47","author":"Lian","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.biomaterials.2011.10.005","article-title":"Targeted non-covalent self-assembled nanoparticles based on human serum albumin","volume":"33","author":"Bunschoten","year":"2012","journal-title":"Biomaterials"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5980","DOI":"10.1021\/acsomega.8b00347","article-title":"Self-Assembly of a Dentinogenic Peptide Hydrogel","volume":"3","author":"Nguyen","year":"2018","journal-title":"ACS Omega"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.ijpharm.2018.07.043","article-title":"Nanoparticle formulations that allow for sustained delivery and brain targeting of the neuropeptide oxytocin","volume":"548","author":"Zaman","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1039\/C9TB02250C","article-title":"A self-assembled peptide hydrogel for cytokine sequestration","volume":"8","author":"Kim","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s12272-020-01264-9","article-title":"Hyperthermal paclitaxel-bound albumin nanoparticles co-loaded with indocyanine green and hyaluronidase for treating pancreatic cancers","volume":"44","author":"Kim","year":"2021","journal-title":"Arch. Pharm Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1016\/j.biomaterials.2011.01.027","article-title":"The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer","volume":"32","author":"Venkatesan","year":"2011","journal-title":"Biomaterials"},{"key":"ref_73","first-page":"525","article-title":"Human serum albumin nanoparticles as an efficient noscapine drug delivery system for potential use in breast cancer: Preparation and in vitro analysis","volume":"5","author":"Sebak","year":"2010","journal-title":"Int. J. Nanomed."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.3109\/03639045.2011.645835","article-title":"Optimization of the lyophilization process for long-term stability of solid-lipid nanoparticles","volume":"38","author":"Howard","year":"2012","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.addr.2015.09.012","article-title":"PEGylation as a strategy for improving nanoparticle-based drug and gene delivery","volume":"99","author":"Suk","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.bbi.2020.03.029","article-title":"Chemokine signaling mediated monocyte infiltration affects anxiety-like behavior following blast injury","volume":"88","author":"Murugan","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.joto.2022.09.002","article-title":"Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model","volume":"18","author":"Perumal","year":"2022","journal-title":"J. Otol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1742-2094-10-97","article-title":"Chronic oral administration of minocycline to sheep with ovine CLN6 neuronal ceroid lipofuscinosis maintains pharmacological concentrations in the brain but does not suppress neuroinflammation or disease progression","volume":"10","author":"Kay","year":"2013","journal-title":"J. Neuroinflammation"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4512","DOI":"10.2527\/1991.69114512x","article-title":"Plasma levels of oxytetracycline, doxycycline, and minocycline in pigs after oral administration in feed","volume":"69","author":"Pijpers","year":"1991","journal-title":"J. Anim. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s00418-009-0577-1","article-title":"Cellular organization of normal mouse liver: A histological, quantitative immunocytochemical, and fine structural analysis","volume":"131","author":"Baratta","year":"2009","journal-title":"Histochem. Cell Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.biomaterials.2018.01.039","article-title":"Protecting neurons from cerebral ischemia\/reperfusion injury via nanoparticle-mediated delivery of an siRNA to inhibit microglial neurotoxicity","volume":"161","author":"Wang","year":"2018","journal-title":"Biomaterials"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"113938","DOI":"10.1016\/j.expneurol.2021.113938","article-title":"Animal model of repeated low-level blast traumatic brain injury displays acute and chronic neurobehavioral and neuropathological changes","volume":"349","author":"Ravula","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.apsb.2019.07.003","article-title":"Targeted delivery of hyaluronic acid nanomicelles to hepatic stellate cells in hepatic fibrosis rats","volume":"10","author":"Li","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ijbiomac.2013.04.011","article-title":"Evaluation of safety and efficacy of brain targeted chitosan nanoparticles of minocycline","volume":"59","author":"Nagpal","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chen, T.Y., Chen, M.R., Liu, S.W., Lin, J.Y., Yang, Y.T., Huang, H.Y., Chen, J.K., Yang, C.S., and Lin, K.M. (2020). Assessment of Polyethylene Glycol-Coated Gold Nanoparticle Toxicity and Inflammation In Vivo Using NF-\u03baB Reporter Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218158"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e13128","DOI":"10.14814\/phy2.13128","article-title":"Systemically administered collagen-targeted gold nanoparticles bind to arterial injury following vascular interventions","volume":"5","author":"Meyers","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3389\/fonc.2018.00354","article-title":"pH-Responsive Cross-Linked Low Molecular Weight Polyethylenimine as an Efficient Gene Vector for Delivery of Plasmid DNA Encoding Anti-VEGF-shRNA for Tumor Treatment","volume":"8","author":"Li","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1021\/nl0802741","article-title":"Cellular uptake and cytotoxicity of silica nanotubes","volume":"8","author":"Nan","year":"2008","journal-title":"Nano Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1016\/j.msec.2009.07.001","article-title":"Anti-tumor activity of paclitaxel-loaded chitosan nanoparticles: An in vitro study","volume":"29","author":"Li","year":"2008","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.canlet.2008.05.009","article-title":"Antiangiogenic cancer therapy using tumor vasculature-targeted liposomes encapsulating 3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one, SU5416","volume":"270","author":"Katanasaka","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_91","first-page":"385","article-title":"Comparison of Different Crosslinking Methods for Preparation of Docetaxel-loaded Albumin Nanoparticles","volume":"14","author":"Niknejad","year":"2015","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1155\/2014\/180549","article-title":"Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy","volume":"2014","author":"Lohcharoenkal","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1208\/s12249-019-1581-y","article-title":"Development of Methotrexate and Minocycline-Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis","volume":"21","author":"Janakiraman","year":"2019","journal-title":"AAPS PharmSciTech"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"118821","DOI":"10.1016\/j.ijpharm.2019.118821","article-title":"Understanding intracellular trafficking and anti-inflammatory effects of minocycline chitosan-nanoparticles in human gingival fibroblasts for periodontal disease treatment","volume":"572","author":"Martin","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/chromsci\/bmx033","article-title":"Easy-Assessment of Levofloxacin and Minocycline in Relevant Biomimetic Media by HPLC-UV Analysis","volume":"55","author":"Matos","year":"2017","journal-title":"J. Chromatogr. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"012038","DOI":"10.1088\/1742-6596\/291\/1\/012038","article-title":"Silica nanoparticles with a substrate switchable luminescence","volume":"291","author":"Bochkova","year":"2011","journal-title":"Proc. J. Phys. Conf. Ser."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7376","DOI":"10.1021\/jf100135h","article-title":"Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities","volume":"58","author":"Yen","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2015.02.003","article-title":"Going Beyond the Liver: Progress and Challenges of Targeted Delivery of siRNA Therapeutics","volume":"203","author":"Lorenzer","year":"2015","journal-title":"J Control Release."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1021\/mp800051m","article-title":"Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles","volume":"5","author":"Alexis","year":"2008","journal-title":"Mol. Pharm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0168-3659(01)00451-5","article-title":"Long-circulating poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles with modulated surface charge","volume":"77","author":"Yamamoto","year":"2001","journal-title":"J. Control. Release"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/nbt.3330","article-title":"Principles of nanoparticle design for overcoming biological barriers to drug delivery","volume":"33","author":"Blanco","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1038\/sj.npp.1301377","article-title":"Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer\u2019s disease models","volume":"32","author":"Choi","year":"2007","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1523\/JNEUROSCI.4371-06.2007","article-title":"Minocycline reduces microglial activation and improves behavioral deficits in a transgenic model of cerebral microvascular amyloid","volume":"27","author":"Fan","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.psyneuen.2019.04.021","article-title":"Minocycline inhibits microglial activation and alleviates depressive-like behaviors in male adolescent mice subjected to maternal separation","volume":"107","author":"Han","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neuroscience.2013.08.037","article-title":"Blast Induces Oxidative Stress, Inflammation, Neuronal Loss and Subsequent Short-Term Memory Impairment in Rats","volume":"253","author":"Cho","year":"2013","journal-title":"Neuroscience"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s40478-016-0395-3","article-title":"Neuronal and Glial Changes in The Brain Resulting From Explosive Blast In An Experimental Model","volume":"4","author":"Goodrich","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.nbd.2012.12.002","article-title":"Electrophysiological white matter dysfunction and association with neurobehavioral deficits following low-level primary blast trauma","volume":"52","author":"Park","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/2093-3371-4-9","article-title":"ICH guideline practice: Application of validated RP-HPLC-DAD method for determination of tapentadol hydrochloride in dosage form","volume":"4","author":"Jain","year":"2013","journal-title":"J. Anal. Sci. Technol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jpha.2016.08.001","article-title":"A stability-indicating high performance liquid chromatography method to determine apocynin in nanoparticles","volume":"7","author":"Ronik","year":"2017","journal-title":"J. Pharm. Anal"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0378-4347(99)00547-2","article-title":"High-performance liquid chromatographic assay for minocycline in human plasma and parotid saliva","volume":"738","author":"Valerie","year":"2000","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Nelson, M., Hillen, W., and Greenwald, R. (2001). Tetracyclines in Biology, Chemistry and Medicine, Birkh\u00e4user Basel.","DOI":"10.1007\/978-3-0348-8306-1"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1080\/10826076.2012.678457","article-title":"Separation Differences Among Phenyl Hydride, UDC Cholesterol and Bidentate C8 Stationary Phases for Stability Indicating Methods of Tetracyclines: Journal of Liquid Chromatography & Related Technologies","volume":"36","author":"Young","year":"2013","journal-title":"J. Liq. Chromatogr. Relat. Technol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/13\/3\/402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:42:49Z","timestamp":1760121769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/13\/3\/402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,25]]},"references-count":112,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["brainsci13030402"],"URL":"https:\/\/doi.org\/10.3390\/brainsci13030402","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,25]]}}}