{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:05:38Z","timestamp":1783476338328,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DFG","award":["HA 2549\/21-1\/Vo 926\/3-1"],"award-info":[{"award-number":["HA 2549\/21-1\/Vo 926\/3-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Inflammatory skin diseases, such as psoriasis, atopic dermatitis, and alopecia areata, occur when the regulatory tolerance of the innate immune system is disrupted, resulting in the activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory signaling pathway by interleukin 6 (IL-6) and other key inflammatory cytokines. JAK inhibitors, such as tofacitinib, bind to these enzymes which are coupled to receptors on cell surfaces and block the transcription of inflammatory cytokine-induced genes. The first topical applications are being marketed, yet insufficient effects regarding indications, such as alopecia areata, suggest that improved delivery technologies could help increase the efficacy. In this study, we used sulfated dendritic polyglycerol with caprolactone segments integrated in its backbone (dPGS-PCL), with a molecular weight of 54 kDa, as a degradable carrier to load and solubilize the hydrophobic drug tofacitinib (TFB). TFB loaded in dPGS-PCL (dPGS-PCL@TFB), at a 11 w\/w% loading capacity in aqueous solution, showed in an ex-vivo human skin model better penetration than free TFB in a 30:70 (v\/v) ethanol\/water mixture. We also investigated the anti-inflammatory efficacy of dPGS-PCL@TFB (0.5 w\/w%), dPGS-PCL, and free TFB in the water\/ethanol mixture by measuring their effects on IL-6 and IL-8 release, and STAT3 and STAT5 activation in ex vivo skin models of simulated inflamed human skin. Our results suggest that dPGS-PCL@TFB reduces the activation of STAT3 and STAT5 by increasing the penetration of the tofacitinib. However, no statistically significant differences with respect to the inhibition of IL-6 and IL-8 were observed in this short incubation time.<\/jats:p>","DOI":"10.3390\/ph17010077","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T07:59:20Z","timestamp":1704700760000},"page":"77","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Topical Delivery of Tofacitinib in Dermatology: The Promise of a Novel Therapeutic Class Using Biodegradable Dendritic Polyglycerol Sulfates"],"prefix":"10.3390","volume":"17","author":[{"given":"Fatemeh","family":"Zabihi","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Chemie und Biochemie, Freie Universit\u00e4t Berlin, Takustr. 3, 14195 Berlin, Germany"},{"name":"Clinical Research Center for Hair and Skin Science, Department of Dermatology, Venereology, and Allergy, Charit\u00e9 Universitaetsmedizin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-0860","authenticated-orcid":false,"given":"Mariam","family":"Cherri","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Chemie und Biochemie, Freie Universit\u00e4t Berlin, Takustr. 3, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0999-0261","authenticated-orcid":false,"given":"Xiao","family":"Guo","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Hair and Skin Science, Department of Dermatology, Venereology, and Allergy, Charit\u00e9 Universitaetsmedizin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3903-3240","authenticated-orcid":false,"given":"Fiorenza","family":"Rancan","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Hair and Skin Science, Department of Dermatology, Venereology, and Allergy, Charit\u00e9 Universitaetsmedizin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8703-3275","authenticated-orcid":false,"given":"Fabian","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Pharmacology and Toxicology), Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Stra\u00dfe 2+4, 14195 Berlin, Germany"},{"name":"Core Facility BioSupraMol PharmaMS, Institute of Pharmacy, Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Stra\u00dfe 2+4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5720-5080","authenticated-orcid":false,"given":"Ehsan","family":"Mohammadifar","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Chemie und Biochemie, Freie Universit\u00e4t Berlin, Takustr. 3, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1888-9595","authenticated-orcid":false,"given":"Burkhard","family":"Kleuser","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Pharmacology and Toxicology), Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Stra\u00dfe 2+4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4346-5911","authenticated-orcid":false,"given":"Wolfgang","family":"B\u00e4umer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universit\u00e4t Berlin, Koserstr. 20, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schirner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Chemie und Biochemie, Freie Universit\u00e4t Berlin, Takustr. 3, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Vogt","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Hair and Skin Science, Department of Dermatology, Venereology, and Allergy, Charit\u00e9 Universitaetsmedizin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-162X","authenticated-orcid":false,"given":"Rainer","family":"Haag","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Chemie und Biochemie, Freie Universit\u00e4t Berlin, Takustr. 3, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nature05893","article-title":"Skin deep but complex","volume":"449","author":"Baumgarth","year":"2007","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/ACI.0b013e3282ef869e","article-title":"Interleukin-17 in inflammatory skin disorders","volume":"7","author":"Teunissen","year":"2007","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/nature05663","article-title":"Pathogenesis and therapy of psoriasis","volume":"445","author":"Lowes","year":"2007","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13223-018-0281-6","article-title":"Atopic dermatitis","volume":"14","author":"Kapur","year":"2018","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4103\/ijt.ijt_99_17","article-title":"Alopecia Areata: Review of Epidemiology, Clinical Features, Pathogenesis, and New Treatment Options","volume":"10","author":"Darwin","year":"2018","journal-title":"Int. J. Trichol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/all.15104","article-title":"T-cell subsets in the skin and their role in inflammatory skin disorders","volume":"77","author":"Aerts","year":"2022","journal-title":"Allergy"},{"key":"ref_7","first-page":"197","article-title":"Getting Under the Skin: Targeting Cutaneous Autoimmune Disease","volume":"93","author":"Vesely","year":"2020","journal-title":"Yale J. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jaci.2020.05.009","article-title":"Mechanisms of skin autoimmunity: Cellular and soluble immune components of the skin","volume":"146","author":"Gudjonsson","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nri2622","article-title":"Skin immune sentinels in health and disease","volume":"9","author":"Nestle","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tanaka, T., Narazaki, M., and Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a016295"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Johnson, B.Z., Stevenson, A.W., Pr\u00eale, C.M., Fear, M.W., and Wood, F.M. (2020). The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing. Biomedicines, 8.","DOI":"10.3390\/biomedicines8050101"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jdermsci.2014.08.012","article-title":"Human skin dendritic cells in health and disease","volume":"77","author":"Haniffa","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.3389\/fimmu.2019.02342","article-title":"Targeting the Janus Kinase Family in Autoimmune Skin Diseases","volume":"10","author":"Howell","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jaad.2016.12.005","article-title":"JAK inhibitors in dermatology: The promise of a new drug class","volume":"76","author":"Damsky","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41584-020-0419-z","article-title":"Translating IL-6 biology into effective treatments","volume":"16","author":"Choy","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41573-020-0082-8","article-title":"Kinase inhibition in autoimmunity and inflammation","volume":"20","author":"Zarrin","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.3389\/fimmu.2019.02847","article-title":"Emerging Topical and Systemic JAK Inhibitors in Dermatology","volume":"10","author":"Solimani","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.exer.2015.12.005","article-title":"Anti-inflammatory effect of topical administration of tofacitinib on corneal inflammation","volume":"145","author":"Sakimoto","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2147\/ITT.S229667","article-title":"Emerging Role of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis","volume":"9","author":"Singh","year":"2020","journal-title":"Immunotargets Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.1021\/jm401490p","article-title":"Discovery and Development of Janus Kinase (JAK) Inhibitors for Inflammatory Diseases","volume":"57","author":"Clark","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1080\/09546634.2018.1546043","article-title":"JAK-inhibitors in dermatology. Current evidence and future applications","volume":"30","author":"Ciechanowicz","year":"2019","journal-title":"J. Dermatol. Treat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2000160","DOI":"10.1002\/adtp.202000160","article-title":"Nanomedicine Approaches to Negotiate Local Biobarriers for Topical Drug Delivery","volume":"4","author":"Mustfa","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"120152","DOI":"10.1016\/j.ijpharm.2020.120152","article-title":"Enhancing intradermal delivery of tofacitinib citrate: Comparison between powder-loaded hollow microneedle arrays and dissolving microneedle arrays","volume":"593","author":"Mallon","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s43094-021-00325-0","article-title":"Design of experiment-driven stability-indicating RP-HPLC method for the determination of tofacitinib in nanoparticles and skin matrix","volume":"7","author":"Gorantla","year":"2021","journal-title":"Future J. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1111\/bjd.14871","article-title":"Topical tofacitinib for atopic dermatitis: A phase IIa randomized trial","volume":"175","author":"Bissonnette","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Szalus, K., Trzeciak, M., and Nowicki, R.J. (2020). JAK-STAT Inhibitors in Atopic Dermatitis from Pathogenesis to Clinical Trials Results. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111743"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Christmann, R., Ho, D.K., Wilzopolski, J., Lee, S., Koch, M., Loretz, B., Vogt, T., B\u00e4umer, W., Schaefer, U.F., and Lehr, C.M. (2020). Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12121131"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.coph.2004.03.005","article-title":"Inhibition of IL-6 for the treatment of inflammatory diseases","volume":"4","author":"Nishimoto","year":"2004","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4103\/2229-5178.120635","article-title":"Nanocarriers and nanoparticles for skin care and dermatological treatments","volume":"4","author":"Gupta","year":"2013","journal-title":"Indian Dermatol. Online J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1021\/acsanm.1c00693","article-title":"Amphiphilic Co-polypeptides Self-Assembled into Spherical Nanoparticles for Dermal Drug Delivery","volume":"4","author":"Ahmadi","year":"2021","journal-title":"ACS Appl. Nano Mater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1080\/17435390.2017.1292371","article-title":"Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes","volume":"11","author":"Gerecke","year":"2017","journal-title":"Nanotoxicology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jconrel.2016.06.030","article-title":"Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing","volume":"242","author":"Gerecke","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7375","DOI":"10.1039\/C7PY01470H","article-title":"One-pot and gram-scale synthesis of biodegradable polyglycerols under ambient conditions: Nanocarriers for intradermal drug delivery","volume":"8","author":"Mohammadifar","year":"2017","journal-title":"Polym. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.3762\/bjnano.5.245","article-title":"Interaction of dermatologically relevant nanoparticles with skin cells and skin","volume":"5","author":"Vogt","year":"2014","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s00403-011-1163-7","article-title":"Nanoparticles in dermatology","volume":"303","author":"Papakostas","year":"2011","journal-title":"Arch. Dermatol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"16848","DOI":"10.1039\/C8NR05536J","article-title":"Synthesis of poly(lactide-co-glycerol) as a biodegradable and biocompatible polymer with high loading capacity for dermal drug delivery","volume":"10","author":"Zabihi","year":"2018","journal-title":"Nanoscale"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7137","DOI":"10.2147\/IJN.S330716","article-title":"Topical Delivery of Rapamycin by Means of Microenvironment-Sensitive Core-Multi-Shell Nanocarriers: Assessment of Anti-Inflammatory Activity in an ex vivo Skin\/T Cell Co-Culture Model","volume":"16","author":"Rancan","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1002\/adhm.201500503","article-title":"Shell Cleavable Dendritic Polyglycerol Sulfates Show High Anti-Inflammatory Properties by Inhibiting L-Selectin Binding and Complement Activation","volume":"4","author":"Reimann","year":"2015","journal-title":"Adv. Healthc. Mater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1002\/eji.1830221139","article-title":"Selective and differential binding of interleukin (IL)-1 alpha, IL-1 beta, IL-2 and IL-6 to glycosaminoglycans","volume":"22","author":"Ramsden","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"FNL31","DOI":"10.2217\/fnl-2019-0008","article-title":"Dendritic polyglycerols are modulators of microglia-astrocyte crosstalk","volume":"14","author":"Maysinger","year":"2019","journal-title":"Future Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1021\/acschemneuro.7b00301","article-title":"Dendritic Polyglycerol Sulfates in the Prevention of Synaptic Loss and Mechanism of Action on Glia","volume":"9","author":"Maysinger","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4779","DOI":"10.1016\/j.biomaterials.2007.07.046","article-title":"In vivo biological evaluation of high molecular weight hyperbranched polyglycerols","volume":"28","author":"Kainthan","year":"2007","journal-title":"Biomaterials"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1021\/acsbiomaterials.1c00439","article-title":"Biodegradable Dendritic Polyglycerol Sulfate for the Delivery and Tumor Accumulation of Cytostatic Anticancer Drugs","volume":"7","author":"Cherri","year":"2021","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jconrel.2016.11.013","article-title":"Tumor-targeted delivery of sunitinib base enhances vaccine therapy for advanced melanoma by remodeling the tumor microenvironment","volume":"245","author":"Huo","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ejpb.2016.12.012","article-title":"Assessment of skin barrier function and biochemical changes of ex vivo human skin in response to physical and chemical barrier disruption","volume":"116","author":"Avetisyan","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jconrel.2016.07.033","article-title":"Intradermal drug delivery by nanogel-peptide conjugates; specific and efficient transport of temoporfin","volume":"242","author":"Zabihi","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/cei\/uxac085","article-title":"Tofacitinib treatment modulates the levels of several inflammation-related plasma proteins in rheumatoid arthritis and baseline levels of soluble biomarkers associate with the treatment response","volume":"210","author":"Valli","year":"2022","journal-title":"Clin. Exp. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5617431","DOI":"10.1155\/2019\/5617431","article-title":"Changes in Serum Cytokines May Predict Therapeutic Efficacy of Tofacitinib in Rheumatoid Arthritis","volume":"2019","author":"Li","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.4049\/jimmunol.1200310","article-title":"Inhibition of JAKs in macrophages increases lipopolysaccharide-induced cytokine production by blocking IL-10-mediated feedback","volume":"189","author":"Pattison","year":"2012","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.3389\/fimmu.2019.01862","article-title":"Tyrosine Kinases in Autoimmune and Inflammatory Skin Diseases","volume":"10","author":"Szilveszter","year":"2019","journal-title":"Front. Immunol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/1\/77\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:42:02Z","timestamp":1760103722000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/1\/77"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,8]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ph17010077"],"URL":"https:\/\/doi.org\/10.3390\/ph17010077","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,8]]}}}