{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:51:08Z","timestamp":1784170268088,"version":"3.55.0"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["R01NS120676"],"award-info":[{"award-number":["R01NS120676"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: The neuropeptide oxytocin has been identified as a potential therapeutic molecule. However, the therapeutic potential of this molecule is limited due to the challenges faced in oxytocin delivery to the brain. Scientific innovation has led to the breakthrough discovery of many modalities to encapsulate molecules for targeted drug delivery, which can enhance oxytocin delivery to the brain. This research aimed to explore a microfluidics-based system that optimizes the formulation of cross-linked bovine serum albumin (BSA) nanoparticles encapsulating oxytocin. Methods: First, the formulation parameters were optimized using a design of experiments (DOE) by evaluating the effect of flow rate, polymer concentration, and the binary solvent mixture polarity on the nanoparticle size. Drug encapsulation efficiency, release, and kinetics profile were characterized. These oxytocin nanoparticles were conjugated to rabies virus glycoprotein (RVG), a brain-targeting ligand, and the conjugation efficiency was determined. Results: The sizes of the nanoparticles were between 50 nm and 75 nm with a &lt;0.4 polydispersity index. The encapsulation efficiency was &gt;80%. Approximately 58% of oxytocin was released from the nanoparticles within the first six hours, showing an initial burst that is ideal for seizure control and thereafter exhibiting the Korsmeyer\u2013Peppas release kinetics. Conclusions: For the first time, we demonstrated the microfluidics method of formulating nanoparticles with particle size of less than 100 nm, with improved encapsulation efficiency and optimal release profile for oxytocin brain delivery.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040452","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T08:21:41Z","timestamp":1743495701000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Microfluidics-Assisted Formulation of Polymeric Oxytocin Nanoparticles for Targeted Brain Delivery"],"prefix":"10.3390","volume":"17","author":[{"given":"Emmanuel","family":"Adediran","sequence":"first","affiliation":[{"name":"Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-4157","authenticated-orcid":false,"given":"Sharon","family":"Vijayanand","sequence":"additional","affiliation":[{"name":"Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2314-3867","authenticated-orcid":false,"given":"Akanksha","family":"Kale","sequence":"additional","affiliation":[{"name":"Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahek","family":"Gulani","sequence":"additional","affiliation":[{"name":"Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0602-6351","authenticated-orcid":false,"given":"Jennifer C.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Pediatrics, Emory University and Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Escayg","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8143-0541","authenticated-orcid":false,"given":"Kevin S.","family":"Murnane","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1039\/C9RA10857B","article-title":"PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: Effects of formulation parameters","volume":"10","year":"2020","journal-title":"RSC Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1039\/C8RA08972H","article-title":"Microfluidic assisted synthesis of PLGA drug delivery systems","volume":"9","author":"Rezvantalab","year":"2019","journal-title":"RSC Adv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"112243","DOI":"10.1016\/j.msec.2021.112243","article-title":"Evaluation of the Benefits of Microfluidic-Assisted Preparation of Polymeric Nanoparticles for DNA Delivery","volume":"127","author":"Zoqlam","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ejps.2011.10.002","article-title":"Albumin nanoparticles carrying cyclodextrins for nasal delivery of the anti-Alzheimer drug tacrine","volume":"44","author":"Luppi","year":"2011","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8593","DOI":"10.1016\/j.biomaterials.2011.07.057","article-title":"Strategies for the nanoencapsulation of hydrophilic molecules in polymer-based nanoparticles","volume":"32","author":"Vrignaud","year":"2011","journal-title":"Biomaterials"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Han, F.Y., Xu, W., Kumar, V., Cui, C.S., Li, X., Jiang, X., Woodruff, T.M., Whittaker, A.K., and Smith, M.T. (2021). Optimisation of a Microfluidic Method for the Delivery of a Small Peptide. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091505"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.patrec.2017.03.023","article-title":"A new approach to characterize epileptic seizures using analytic time-frequency flexible wavelet transform and fractal dimension","volume":"94","author":"Sharma","year":"2017","journal-title":"Pattern Recognit. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/sj.npp.1300021","article-title":"Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger\u2019s Disorders","volume":"28","author":"Hollander","year":"2003","journal-title":"Neuropsychopharmacology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.neuron.2010.03.005","article-title":"The Challenge of Translation in Social Neuroscience: A Review of Oxytocin, Vasopressin, and Affiliative Behavior","volume":"65","author":"Insel","year":"2010","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1177\/0269881112473788","article-title":"A brief history of oxytocin and its role in modulating psychostimulant effects","volume":"27","author":"Carson","year":"2013","journal-title":"J. Psychopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41467-020-14845-5","article-title":"Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans","volume":"11","author":"Martins","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.colsurfa.2017.04.062","article-title":"Microfluidic-assisted nanoprecipitation of antiviral-loaded polymeric nanoparticles","volume":"532","author":"Bramosanti","year":"2017","journal-title":"Colloids Surf. Physicochem. Eng. Asp."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.3762\/bjnano.10.220","article-title":"Microfluidics as tool to prepare size-tunable PLGA nanoparticles with high curcumin encapsulation for efficient mucus penetration","volume":"10","author":"Lababidi","year":"2019","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mares, A.G., Pacassoni, G., Marti, J.S., Pujals, S., and Albertazzi, L. (2021). Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251821"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jconrel.2011.07.031","article-title":"Albumin-based nanoparticles as potential controlled release drug delivery systems","volume":"157","author":"Elzoghby","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.biopha.2018.08.106","article-title":"Bovine serum albumin nanoparticles induce histopathological changes and inflammatory cell recruitment in the skin of treated mice","volume":"107","author":"Salvador","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1186\/1556-276X-9-343","article-title":"Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear","volume":"9","author":"Yu","year":"2014","journal-title":"Nanoscale Res. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cho, H., Jeon, S.I., Ahn, C.-H., Shim, M.K., and Kim, K. (2022). Emerging Albumin-Binding Anticancer Drugs for Tumor-Targeted Drug Delivery: Current Understandings and Clinical Translation. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040728"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ijpharm.2017.09.054","article-title":"Technical aspects of preparing PEG-PLGA nanoparticles as carrier for chemotherapeutic agents by nanoprecipitation method","volume":"533","author":"Almoustafa","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ijpharm.2018.08.044","article-title":"A comparative assessment of continuous production techniques to generate sub-micron size PLGA particles","volume":"550","author":"Operti","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1208\/s12249-014-0177-9","article-title":"Nanomedicine Scale-up Technologies: Feasibilities and Challenges","volume":"15","author":"Paliwal","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jconrel.2010.08.011","article-title":"RVG peptide tethered bioreducible polyethylenimine for gene delivery to brain","volume":"155","author":"Son","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.cherd.2019.11.031","article-title":"A review on novel methodologies for drug nanoparticle preparation: Microfluidic approach","volume":"153","author":"Shrimal","year":"2020","journal-title":"Chem. Eng. Res. Des."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10671","DOI":"10.1021\/nn403370e","article-title":"Microfluidic Platform for Combinatorial Synthesis and Optimization of Targeted Nanoparticles for Cancer Therapy","volume":"7","author":"Valencia","year":"2013","journal-title":"ACS Nano"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2017.09.013","article-title":"Recent advances of controlled drug delivery using microfluidic platforms","volume":"128","author":"Sanjay","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1021\/acsabm.9b00853","article-title":"Microfluidic Methods for Fabrication and Engineering of Nanoparticle Drug Delivery Systems","volume":"3","author":"Zhang","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5045","DOI":"10.1016\/j.polymer.2012.08.039","article-title":"Improved size-tunable preparation of polymeric nanoparticles by microfluidic nanoprecipitation","volume":"53","author":"Bally","year":"2012","journal-title":"Polymer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11095-018-2358-9","article-title":"Double or Simple Emulsion Process to Encapsulate Hydrophilic Oxytocin Peptide in PLA-PEG Nanoparticles","volume":"35","author":"Gourdon","year":"2018","journal-title":"Pharm. Res."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.yhbeh.2018.12.011","article-title":"Nanoparticle encapsulation increases the brain penetrance and duration of action of intranasal oxytocin","volume":"108","author":"Zaman","year":"2019","journal-title":"Horm. Behav."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wong, J.C., Shapiro, L., Thelin, J.T., Heaton, E.C., Zaman, R.U., D\u2019Souza, M.J., Murnane, K.S., and Escayg, A. (2021). Nanoparticle encapsulated oxytocin increases resistance to induced seizures and restores social behavior in Scn1a-derived epilepsy. Neurobiol. Dis., 147.","DOI":"10.1016\/j.nbd.2020.105147"},{"key":"ref_33","first-page":"315","article-title":"Oxytocin Reduces Seizure Burden and Hippocampal Injury in a Rat Model of Perinatal Asphyxia","volume":"14","author":"Panaitescu","year":"2018","journal-title":"Acta Endocrinol. Buchar."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1021\/acschemneuro.2c00124","article-title":"Protective Effects of Intranasally Administrated Oxytocin-Loaded Nanoparticles on Pentylenetetrazole-Kindling Epilepsy in Terms of Seizure Severity, Memory, Neurogenesis, and Neuronal Damage","volume":"13","author":"Sahin","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104324","DOI":"10.1016\/j.phrs.2019.104324","article-title":"Oxytocin delivered nasally or intraperitoneally reaches the brain and plasma of normal and oxytocin knockout mice","volume":"146","author":"Smith","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"33246","DOI":"10.1039\/C9RA06279C","article-title":"Microfluidic synthesis of PLGA\/carbon quantum dot microspheres for vascular endothelial growth factor delivery","volume":"9","author":"Omidi","year":"2019","journal-title":"RSC Adv."},{"key":"ref_37","unstructured":"(2025, March 25). Cytotoxicity Assay. Available online: https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/cytotoxicity-assay."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5262","DOI":"10.1039\/c3nr01289a","article-title":"A microfluidic origami chip for synthesis of functionalized polymeric nanoparticles","volume":"5","author":"Sun","year":"2013","journal-title":"Nanoscale"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nair, S.C., Vinayan, K.P., and Mangalathillam, S. (2021). Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101640"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40580-016-0061-2","article-title":"Polymeric nanoparticles containing diazepam: Preparation, optimization, characterization, in-vitro drug release and release kinetic study","volume":"3","author":"Bohrey","year":"2016","journal-title":"Nano Converg."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tarhini, M., Benlyamani, I., Hamdani, S., Agusti, G., Fessi, H., Greige-Gerges, H., Bentaher, A., and Elaissari, A. (2018). Protein-Based Nanoparticle Preparation via Nanoprecipitation Method. Materials, 11.","DOI":"10.3390\/ma11030394"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1007\/s11095-008-9692-2","article-title":"Preparation of BMP-2 Containing Bovine Serum Albumin (BSA) Nanoparticles Stabilized by Polymer Coating","volume":"25","author":"Wang","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.colsurfa.2012.07.022","article-title":"Investigation and modeling effective parameters influencing the size of BSA protein nanoparticles as colloidal carrier","volume":"412","author":"Rahimnejad","year":"2012","journal-title":"Colloids Surf. Physicochem. Eng. Asp."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16330","DOI":"10.1021\/ja806586v","article-title":"Swelling the Micelle Core Surrounding Single-Walled Carbon Nanotubes with Water-Immiscible Organic Solvents","volume":"130","author":"Wang","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.tifs.2013.10.002","article-title":"Production of nanoparticles by anti-solvent precipitation for use in food systems","volume":"34","author":"Joye","year":"2013","journal-title":"Trends Food Sci. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1039\/b906556n","article-title":"Synthetic polymeric nanoparticles by nanoprecipitation","volume":"19","author":"Hornig","year":"2009","journal-title":"J. Mater. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1007\/s11051-011-0354-7","article-title":"Self-assembling process of flash nanoprecipitation in a multi-inlet vortex mixer to produce drug-loaded polymeric nanoparticles","volume":"13","author":"Shen","year":"2011","journal-title":"J. Nanopart. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ces.2017.04.046","article-title":"Fundamental studies on throughput capacities of hydrodynamic flow-focusing microfluidics for producing monodisperse polymer nanoparticles","volume":"169","author":"Baby","year":"2017","journal-title":"Chem. Eng. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gimondi, S., Guimar\u00e3es, C.F., Vieira, S.F., Gon\u00e7alves, V.M.F., Tiritan, M.E., Reis, R.L., Ferreira, H., and Neves, N.M. (2022). Microfluidic mixing system for precise PLGA-PEG nanoparticles size control. Nanomed. Nanotechnol. Biol. Med., 40.","DOI":"10.1016\/j.nano.2021.102482"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1021\/nn800275r","article-title":"Self-assembled lipid--polymer hybrid nanoparticles: A robust drug delivery platform","volume":"2","author":"Zhang","year":"2008","journal-title":"ACS Nano"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1002\/chem.202001146","article-title":"A Microfluidic Co-Flow Route for Human Serum Albumin-Drug\u2013Nanoparticle Assembly","volume":"26","author":"Hakala","year":"2020","journal-title":"Chem. Eur. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s11671-020-03370-5","article-title":"Synthesis of Various Size Gold Nanoparticles by Chemical Reduction Method with Different Solvent Polarity","volume":"15","author":"Hussain","year":"2020","journal-title":"Nanoscale Res. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0378-5173(03)00134-0","article-title":"Optimization of the preparation process for human serum albumin (HSA) nanoparticles","volume":"257","author":"Langer","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"45","DOI":"10.15171\/ijb.1168","article-title":"The Effects of Organic Solvents on the Physicochemical Properties of Human Serum Albumin Nanoparticles","volume":"14","author":"Shojaosadati","year":"2016","journal-title":"Iran. J. Biotechnol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.jcis.2022.05.007","article-title":"Peptide loaded polymeric nanoparticles by non-aqueous nanoprecipitation","volume":"622","author":"Rottenberg","year":"2022","journal-title":"J. Colloid Interface Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/pi.4822","article-title":"Preparation of polymeric nanoparticles by novel electrospray nanoprecipitation: Novel electrospray nanoprecipitation","volume":"64","author":"Luo","year":"2015","journal-title":"Polym. Int."},{"key":"ref_57","unstructured":"Mahadevan-Jansen, A., Vo-Dinh, T., and Grundfest, W.S. (2009). Support vector machine based classification of fast Fourier transform spectroscopy of proteins. Advanced Biomedical and Clinical Diagnostic Systems VII, SPIE."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Chung, E.P., Cotter, J.D., Prakapenka, A.V., Cook, R.L., DiPerna, D.M., and Sirianni, R.W. (2020). Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020093"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8505","DOI":"10.1039\/D1RA00550B","article-title":"Application progress of RVG peptides to facilitate the delivery of therapeutic agents into the central nervous system","volume":"11","author":"Wang","year":"2021","journal-title":"RSC Adv."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2174\/2211738507666191019141049","article-title":"Utilization of Microfluidics for the Preparation of Polymeric Nanoparticles for the Antioxidant Rutin: A Comparison with Bulk Production","volume":"7","author":"Vu","year":"2019","journal-title":"Pharm. Nanotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.ejpb.2012.11.006","article-title":"Optimization of encapsulation of a synthetic long peptide in PLGA nanoparticles: Low-burst release is crucial for efficient CD8+ T cell activation","volume":"83","author":"Silva","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/4\/452\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:07:35Z","timestamp":1760029655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/4\/452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["pharmaceutics17040452"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17040452","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]}}}