{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T21:21:19Z","timestamp":1793481679143,"version":"4.5.0"},"reference-count":53,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","award":["315-26922-2BS3-242"],"award-info":[{"award-number":["315-26922-2BS3-242"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Methotrexate (MTX) is the first line agent for therapy against rheumatoid arthritis (RA); however, orally its efficacy is hampered by poor solubility, less permeability, short plasma half-life, and reduced bioavailability. Meanwhile, parenteral formulations are associated with severe adverse effects. In an attempt to improve the efficacy of MTX, we synthesized polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer by a ring-opening copolymerization reaction and used it as a carrier for the fabrication of MTX-loaded nanomicelles. Surfactant-free, self-assembled nanomicelles were prepared by nanoprecipitation technique and optimized through central composite design. The optimized nanomicelles exhibited a size distribution of 31 nm and an encapsulation efficiency of 91%. In vitro, the nanomicelles exhibited hemocompatibility, sustained release, and significantly high uptake in lipopolysaccharide activated macrophages. To facilitate application on the skin, optimized nanomicelles were loaded into a Carbopol 934-based hydrogel with eucalyptus oil as a penetration enhancer. Eucalyptus oil significantly improved the permeation of nanomicelles through the skin (p &amp;lt; 0.001). When the hydrogel was applied on the RA mice model, nanomicelles exhibited preferentially highest accumulation in the inflamed joints than other organs. As compared with the free MTX, MTX nanomicelles significantly improved the pharmacokinetic (4.34-fold greater half-life, 3.68-fold higher AUC0\u2013t, and 3.15-fold higher mean residence time) and pharmacodynamic profile ascertained through low inflammatory cytokines expression, improved oxidation protection, recovered behavioral responses, and radiological analysis. MTX nanomicelles-based hydrogel also significantly reduced the hepatotoxicity and did not activate the immune system. These results suggest that the MTX-loaded nanomicelles-based transdermal hydrogel can prove to be a promising agent against RA.<\/jats:p>","DOI":"10.1021\/acsnano.0c00364","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T12:43:41Z","timestamp":1585053821000},"page":"4662-4681","source":"Crossref","is-referenced-by-count":150,"title":["Surfactant-Free,\nSelf-Assembled Nanomicelles-Based\nTransdermal Hydrogel for Safe and Targeted Delivery of Methotrexate\nagainst Rheumatoid Arthritis"],"prefix":"10.1021","volume":"14","author":[{"given":"Maimoona","family":"Qindeel","sequence":"first","affiliation":[{"name":"Quaid-i-Azam University , , ,","place":["Islamabad, Pakistan, 45320"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dildar","family":"Khan","sequence":"additional","affiliation":[{"name":"Quaid-i-Azam University , , ,","place":["Islamabad, Pakistan, 45320"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Quaid-i-Azam University , , ,","place":["Islamabad, Pakistan, 45320"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman","family":"Khan","sequence":"additional","affiliation":[{"name":"Quaid-i-Azam University , , ,","place":["Islamabad, Pakistan, 45320"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-0359","authenticated-orcid":true,"family":"Asim.ur.Rehman","sequence":"additional","affiliation":[{"name":"Quaid-i-Azam University , , ,","place":["Islamabad, Pakistan, 45320"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"2026081718105581900_cit1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1097\/BOR.0000000000000664","article-title":"Evolving Concepts of the Pathogenesis of Rheumatoid\nArthritis with Focus on the Early and Late Stages","volume":"32","author":"Coutant","year":"2020","journal-title":"Curr. Opin. Rheumatol."},{"key":"2026081718105581900_cit2","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1038\/s41467-018-02892-y","article-title":"Functionally Distinct\nDisease-Associated Fibroblast\nSubsets in Rheumatoid Arthritis","volume":"9","author":"Mizoguchi","year":"2018","journal-title":"Nat. Commun."},{"key":"2026081718105581900_cit3","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/s00223-017-0373-1","article-title":"Bone Loss\nin Rheumatoid Arthritis:\nBasic Mechanisms and Clinical Implications","volume":"102","author":"Shim","year":"2018","journal-title":"Calcif. Tissue Int."},{"key":"2026081718105581900_cit4","doi-asserted-by":"publisher","first-page":"3312","DOI":"10.3390\/ijms20133312","article-title":"Preparation and In Vitro\/In\nVivo Characterization of Polymeric Nanoparticles Containing\nMethotrexate to Improve Lymphatic Delivery","volume":"20","author":"Jang","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2026081718105581900_cit5","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1080\/21691401.2018.1471482","article-title":"De-Esterified\nTragacanth-Chitosan\nNano-Hydrogel for Methotrexate Delivery; Optimization of the Formulation\nby Taguchi Design","volume":"46","author":"Sadrjavadi","year":"2018","journal-title":"Artif. Cells, Nanomed., Biotechnol."},{"key":"2026081718105581900_cit6","doi-asserted-by":"publisher","first-page":"302","DOI":"10.3390\/pharmaceutics11070302","article-title":"Controlled\nDrug Delivery Systems for Oral Cancer Treatment-Current\nStatus and Future Perspectives","volume":"11","author":"Ketabat","year":"2019","journal-title":"Pharmaceutics"},{"key":"2026081718105581900_cit7","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.intimp.2014.11.018","article-title":"Combination\nof Coenzyme Q10 with Methotrexate Suppresses Freund\u2019s Complete\nAdjuvant-Induced Synovial Inflammation with Reduced Hepatotoxicity\nin Rats: Effect on Oxidative Stress and Inflammation","volume":"24","author":"Tawfik","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"2026081718105581900_cit8","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.ccr.2018.01.007","article-title":"Emerging\nNanomaterials\nwith Advanced Drug Delivery Functions; Focused on Methotrexate Delivery","volume":"359","author":"Choi","year":"2018","journal-title":"Coord. Chem. Rev."},{"key":"2026081718105581900_cit9","first-page":"261","article-title":"Intrarticular Methotrexate\nin the Therapy of Rheumatoid\nArthritis","volume":"80","author":"Franchi","year":"1989","journal-title":"Recenti Progr. Med."},{"key":"2026081718105581900_cit10","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s10787-018-0459-z","article-title":"Predicting\nMethotrexate Resistance\nin Rheumatoid Arthritis Patients","volume":"26","author":"Yu","year":"2018","journal-title":"Inflammopharmacology"},{"key":"2026081718105581900_cit11","doi-asserted-by":"publisher","first-page":"108770","DOI":"10.1016\/j.biopha.2019.108770","article-title":"Enhanced Skin\nPermeation of Methotrexate\nfrom Penetration Enhancer Containing Vesicles: In Vitro Optimization and In Vivo Evaluation","volume":"114","author":"Sadarani","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"2026081718105581900_cit12","first-page":"166","article-title":"Liposomal Methotrexate\nHydrogel for Treatment of Localized Psoriasis: Preparation, Characterization\nand Laser Targeting","volume":"14","author":"Ali","year":"2008","journal-title":"Med. Sci. Monit."},{"key":"2026081718105581900_cit13","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.ijpharm.2003.10.006","article-title":"Deformable\nLiposomes for Dermal Administration of Methotrexate","volume":"270","author":"Trotta","year":"2004","journal-title":"Int. J. Pharm."},{"key":"2026081718105581900_cit14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.ijpharm.2010.08.011","article-title":"Nanogel Particulates\nLocated within\nDiffusion Cell Receptor Phases Following Topical Application Demonstrates\nUptake into and Migration Across Skin","volume":"401","author":"Samah","year":"2010","journal-title":"Int.\nJ. Pharm."},{"key":"2026081718105581900_cit15","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.ejpb.2012.05.016","article-title":"Transdermal Delivery of the Anti-Rheumatic\nAgent Methotrexate Using a Solid-in-Oil Nanocarrier","volume":"82","author":"Yang","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"2026081718105581900_cit16","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.ijpharm.2015.12.061","article-title":"Nanostructured Lipid\nCarrier Mediates Effective Delivery of Methotrexate to Induce Apoptosis\nof Rheumatoid Arthritis via NF-\u03baB and FOXO1","volume":"499","author":"Garg","year":"2016","journal-title":"Int. J. Pharm."},{"key":"2026081718105581900_cit17","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jconrel.2016.03.035","article-title":"Targeted Delivery of Low-Dose Dexamethasone\nUsing PCL-PEG Micelles\nfor Effective Treatment of Rheumatoid Arthritis","volume":"230","author":"Wang","year":"2016","journal-title":"J. Controlled Release"},{"key":"2026081718105581900_cit18","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.2217\/nnm-2018-0490","article-title":"Ligand\nDecorated\nChitosan as an Advanced Nanocarrier for Targeted Delivery: A Critical\nReview","volume":"14","author":"Qindeel","year":"2019","journal-title":"Nanomedicine"},{"key":"2026081718105581900_cit19","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1201\/9781315374215","article-title":"Topical and\nTrasndermal Drug Delivery","volume-title":"Dermal Drug Delivery:\nFrom Innovation to Production","author":"Ghosh","year":"2020"},{"key":"2026081718105581900_cit20","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1111\/jphp.12334","article-title":"Essential Oils and\nTheir Constituents as Skin Penetration\nEnhancer for Transdermal Drug Delivery: A Review","volume":"67","author":"Herman","year":"2015","journal-title":"J. Pharm. Pharmacol."},{"key":"2026081718105581900_cit21","doi-asserted-by":"publisher","first-page":"173","DOI":"10.4314\/tjpr.v8i2.44527","article-title":"Chemical Penetration Enhancers for Transdermal Drug\nDelivery Systems","volume":"8","author":"Pathan","year":"2009","journal-title":"Trop. J. Pharm. Res."},{"key":"2026081718105581900_cit22","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.colsurfb.2019.02.008","article-title":"Synthesis\nand Colloidal Characterization of\nFolic Acid-Modified PEG-b-PCL Micelles for Methotrexate Delivery","volume":"177","author":"Brandt","year":"2019","journal-title":"Colloids Surf., B"},{"key":"2026081718105581900_cit23","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ejpb.2018.06.020","article-title":"Dual-Functional Lipid\nPolymeric Hybrid pH-Responsive Nanoparticles\nDecorated with Cell Penetrating Peptide and Folate for Therapy against\nRheumatoid Arthritis","volume":"130","author":"Zhao","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"2026081718105581900_cit24","doi-asserted-by":"publisher","first-page":"153","DOI":"10.22038\/IJBMS.2017.26590.6513","article-title":"Preparation\nand Evaluation of PCL-PEG-PCL Micelles as Potential Nanocarriers for\nOcular Delivery of Dexamethasone","volume":"21","author":"Milani","year":"2018","journal-title":"Iran J. Basic\nMed. Sci."},{"key":"2026081718105581900_cit25","doi-asserted-by":"publisher","first-page":"418","DOI":"10.4103\/2229-5178.190509","article-title":"Methotrexate-Induced\nNonhealing Cutaneous Ulcers in a Nonpsoriatic Patient without Pancytopenia","volume":"7","author":"Tekur","year":"2016","journal-title":"Indian Dermatol. Online J."},{"key":"2026081718105581900_cit26","doi-asserted-by":"crossref","first-page":"435","DOI":"10.5070\/D3207023133","article-title":"Cutaneous Erosions:\nA Herald for Impending Pancytopenia\nin Methotrexate Toxicity","volume":"20","author":"Shiver","year":"2014","journal-title":"Dermatol. Online J."},{"key":"2026081718105581900_cit27","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1136\/ard.2010.132720","article-title":"Role of\nOxidative Stress in Rheumatoid Arthritis: Insights from the Nrf2-Knockout\nMice","volume":"70","author":"Wruck","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"2026081718105581900_cit28","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.redox.2017.07.018","article-title":"Direct\nAntioxidant Properties\nof Methotrexate: Inhibition of Malondialdehyde-Acetaldehyde-Protein\nAdduct Formation and Superoxide Scavenging","volume":"13","author":"Zimmerman","year":"2017","journal-title":"Redox Biol."},{"key":"2026081718105581900_cit29","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1093\/rheumatology\/37.5.502","article-title":"Methotrexate Reduces Inflammatory Cell Numbers, Expression\nof Monokines and of Adhesion Molecules in Synovial Tissue of Patients\nwith Rheumatoid Arthritis","volume":"37","author":"Dolhain","year":"1998","journal-title":"Rheumatology"},{"key":"2026081718105581900_cit30","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1016\/S0032-3861(03)00087-9","article-title":"Synthesis and Characterization\nof PCL\/PEG\/PCL Triblock Copolymers by Using Calcium Catalyst","volume":"44","author":"Piao","year":"2003","journal-title":"Polymer"},{"key":"2026081718105581900_cit31","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1007\/s10924-020-01683-1","article-title":"New, Environment\nFriendly Approach for Synthesis of Amphiphilic PCL-PEG\u2013PCL\nTriblock Copolymer: An Efficient Carrier for Fabrication of Nanomicelles","volume":"28","author":"Qindeel","year":"2020","journal-title":"J. Polym. Environ."},{"key":"2026081718105581900_cit32","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3390\/polym8090321","article-title":"Bactericidal Effect\nof Lauric Acid-Loaded\nPCL-PEG-PCL Nano-Sized Micelles on Skin Commensal Propionibacterium\nAcnes","volume":"8","author":"Tran","year":"2016","journal-title":"Polymers"},{"key":"2026081718105581900_cit33","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1080\/03639045.2019.1569031","article-title":"Development\nof Novel pH-Sensitive Nanoparticles Loaded Hydrogel for Transdermal\nDrug Delivery","volume":"45","author":"Qindeel","year":"2019","journal-title":"Drug Dev. Ind. Pharm."},{"key":"2026081718105581900_cit34","doi-asserted-by":"publisher","first-page":"3013","DOI":"10.2147\/IJN.S32662","article-title":"Formation of Methotrexate-PLLA-PEG-PLLA\nComposite Microspheres by\nMicroencapsulation through a Process of Suspension-Enhanced Dispersion\nby Supercritical CO2","volume":"7","author":"Chen","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"2026081718105581900_cit35","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1007\/s11095-015-1852-6","article-title":"Budesonide Loaded\nPLGA Nanoparticles for Targeting\nthe Inflamed Intestinal Mucosa-Pharmaceutical Characterization and\nFluorescence Imaging","volume":"33","author":"Ali","year":"2016","journal-title":"Pharm. Res."},{"key":"2026081718105581900_cit36","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1039\/C5TB02479J","article-title":"Activated Macrophage-Targeted Dextran-Methotrexate\/Folate\nConjugate Prevents Deterioration of Collagen-Induced Arthritis in\nMice","volume":"4","author":"Yang","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"2026081718105581900_cit37","first-page":"1","article-title":"United\nStates Pharmacopeia-National Formulary","volume":"6","author":"Moreton","year":"2016","journal-title":"J. Excip.\nFood Chem."},{"key":"2026081718105581900_cit38","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1021\/js950250r","article-title":"Zero-Order Release\nKinetics from a Self-Correcting\nFloatable Asymmetric Configuration Drug Delivery System","volume":"85","author":"Yang","year":"1996","journal-title":"J. Pharm. Sci."},{"key":"2026081718105581900_cit39","first-page":"15","article-title":"Reactions with\na Simple Kinetic Form","volume-title":"Chemical Kinetics and\nReaction Mechanisms","author":"Espenson","year":"1995"},{"key":"2026081718105581900_cit40","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1002\/jps.2600521210","article-title":"Mechanism\nof Sustained-Action Medication. Theoretical Analysis of Rate of Release\nof Solid Drugs Dispersed in Solid Matrices","volume":"52","author":"Higuchi","year":"1963","journal-title":"J. Pharm. Sci."},{"key":"2026081718105581900_cit41","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/0378-5173(83)90064-9","article-title":"Mechanisms\nof Solute Release from Porous Hydrophilic Polymers","volume":"15","author":"Korsmeyer","year":"1983","journal-title":"Int. J. Pharm."},{"key":"2026081718105581900_cit42","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1021\/ie50260a018","article-title":"Dependence of Reaction Velocity upon\nSurface and Agitation","volume":"23","author":"Hixson","year":"1931","journal-title":"Ind. Eng. Chem."},{"key":"2026081718105581900_cit43","doi-asserted-by":"publisher","first-page":"606","DOI":"10.3390\/pharmaceutics11110606","article-title":"Enhancement in Site-Specific\nDelivery of Carvacrol\nagainst Methicillin Resistant Staphylococcus Aureus Induced Skin Infections Using Enzyme Responsive Nanoparticles: A\nProof of Concept Study","volume":"11","author":"Mir","year":"2019","journal-title":"Pharmaceutics"},{"key":"2026081718105581900_cit44","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1007\/s13204-015-0457-z","article-title":"Novel Isotretinoin\nMicroemulsion-Based Gel for Targeted Topical Therapy of Acne: Formulation\nConsideration, Skin Retention and Skin Irritation Studies","volume":"6","author":"Patel","year":"2016","journal-title":"Appl. Nanosci."},{"key":"2026081718105581900_cit45","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1093\/chromsci\/bmt081","article-title":"Simple and Reliable HPLC Method for\nthe Monitoring\nof Methotrexate in Osteosarcoma Patients","volume":"52","author":"Begas","year":"2014","journal-title":"J.\nChromatogr. Sci."},{"key":"2026081718105581900_cit46","first-page":"40","article-title":"Effect Of Ethanolic Leaf Extract\nof Cocor Bebek (Bryophyllum Pinnatum) on the Attenuation\nof Thermal Hyperalgesia","volume":"1","author":"Wulandari","year":"2018","journal-title":"J. Nutraceut. Herb.\nMed."},{"key":"2026081718105581900_cit47","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.intimp.2018.05.034","article-title":"Attenuation\nof Inflammatory Pain by Puerarin in Animal Model of Inflammation through\nInhibition of Pro-Inflammatory Mediators","volume":"61","author":"Ullah","year":"2018","journal-title":"Int.\nImmunopharmacol."},{"key":"2026081718105581900_cit48","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jchromb.2006.07.054","article-title":"Analysis of\nNitrite and Nitrate in Biological Fluids by Assays Based on the Griess\nReaction: Appraisal of the Griess Reaction in the L-Arginine\/Nitric\nOxide Area of Research","volume":"851","author":"Tsikas","year":"2007","journal-title":"J. Chromatogr. B: Anal.\nTechnol. Biomed. Life Sci."},{"key":"2026081718105581900_cit49","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1016\/S0021-9258(19)42083-8","article-title":"Glutathione S-Transferases\nthe First\nEnzymatic Step in Mercapturic Acid Formation","volume":"249","author":"Habig","year":"1974","journal-title":"J. Biol. Chem."},{"key":"2026081718105581900_cit50","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/0304-4165(79)90289-7","article-title":"Levels of Glutathione, Glutathione\nReductase and Glutathione S-Transferase Activities in Rat Lung and\nLiver","volume":"582","author":"Moron","year":"1979","journal-title":"Biochim. Biophys. Acta, Gen. Subj."},{"key":"2026081718105581900_cit51","doi-asserted-by":"publisher","first-page":"191","DOI":"10.4103\/0971-6580.139808","article-title":"In\nVivo Studies\non the Protective Effect of Propolis on Doxorubicin-Induced Toxicity\nin Liver of Male Rats","volume":"21","author":"Singla","year":"2014","journal-title":"Toxicol. Int."},{"key":"2026081718105581900_cit52","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for\nLipid Peroxides in Animal\nTissues by Thiobarbituric Acid Reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal.\nBiochem."},{"key":"2026081718105581900_cit53","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.ijbiomac.2015.05.001","article-title":"Neuropharmacokinetic Evaluation of\nMethotrexate-Loaded Chitosan Nanogels","volume":"79","author":"Azadi","year":"2015","journal-title":"Int.\nJ. Biol. Macromol."}],"container-title":["ACS Nano"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsnano.0c00364","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/14\/4\/4662\/18464854\/nn0c00364.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/14\/4\/4662\/18464854\/nn0c00364.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:35:39Z","timestamp":1787006139000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancac3\/article\/14\/4\/4662\/601568\/Surfactant-Free-Self-Assembled-Nanomicelles-Based"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,24]]},"references-count":53,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,3,24]]},"published-print":{"date-parts":[[2020,4,28]]}},"URL":"https:\/\/doi.org\/10.1021\/acsnano.0c00364","relation":{},"ISSN":["1936-0851","1936-086X"],"issn-type":[{"value":"1936-0851","type":"print"},{"value":"1936-086X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,24]]}}}