{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:12:51Z","timestamp":1786119171374,"version":"build-2736575974"},"reference-count":104,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Effective management of skin cancer remains challenging due to limited transdermal drug penetration, systemic toxicity, and therapeutic resistance. In this study, 5\u2010fluorouracil (5\u2010FU)\u2010loaded lipid\u2010polymer hybrid nanoparticles (LPHNPs) were rationally engineered as a next\u2010generation nanocarrier system to overcome these barriers. The hybrid design synergistically combines the structural integrity of polymers with the biocompatibility and permeability\u2010enhancing attributes of lipids. Using a central composite design, formulation parameters were optimized to achieve favorable physicochemical characteristics, yielding nanoparticles with a mean diameter of 256.7\u2009nm, a polydispersity index (PDI) of 0.2711, and a positive zeta potential of +25.47\u2009mV, indicative of excellent colloidal stability. In vitro release and ex vivo permeation studies revealed a sustained drug release profile and significantly improved dermal penetration compared to conventional formulations. Moreover, the Hen's egg test\u2010chorioallantoic membrane (HET\u2010CAM) irritation assay confirmed the biocompatibility and reduced irritation potential of the developed system. Overall, the optimized 5\u2010FU\u2010loaded LPHNPs present a promising platform for localized, controlled transdermal chemotherapy, potentially minimizing systemic exposure and improving therapeutic efficacy in skin cancer management.<\/jats:p>","DOI":"10.1002\/ddr.70254","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:58:36Z","timestamp":1773003516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rational Design and Characterization of 5\u2010Fluorouracil\u2013Loaded Lipid\u2013Polymer Hybrid Nanoparticles for Enhanced Transdermal Delivery in Skin Cancer Therapy"],"prefix":"10.1002","volume":"87","author":[{"given":"Tenzin Sonam","family":"Dongsar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Education and Research, Jamia Hamdard New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Pharmacy King Khalid University Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humood Al","family":"Shmrany","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory College of Applied medical sciences Prince Sattam bin Abdulaziz University Alkharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6686-7019","authenticated-orcid":false,"given":"Khang Wen","family":"Goh","sequence":"additional","affiliation":[{"name":"Faculty of Business and Communication INTI International University Nilai Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhan Jalees","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Education and Research, Jamia Hamdard New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0890-769X","authenticated-orcid":false,"given":"Prashant","family":"Kesharwani","sequence":"additional","affiliation":[{"name":"Next\u2010Generation Translational Nanomedicine Laboratory, Department of Pharmaceutical Sciences Dr. Harisingh Gour Vishwavidyalaya (A Central University) Sagar Madhya Pradesh India"},{"name":"Department of Research and Development Asia University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2019.05.041"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCLEPRO.2011.10.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2019.101476"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFA.2014.10.040"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPB.2024.114432"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S271952"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/09205063.2022.2121592"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00403-017-1724-5"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567201816666190201143457"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S52634"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCONREL.2011.06.039"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-443-36326-9.00013-7"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFA.2014.06.029"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/PHARMACEUTICS9020012"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/S13346-012-0105-Z"},{"key":"e_1_2_11_17_1","unstructured":"American Cancer Society. nd. Chemotherapy Side Effects.https:\/\/www.cancer.org\/cancer\/managing-cancer\/treatment-types\/chemotherapy\/chemotherapy-side-effects.html."},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOMATERIALS.2012.02.059"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1441"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/S40005-017-0370-4"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-3659(95)00158-1"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.MPMED.2017.04.003"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1515\/NTREV-2020-0117"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/S13205-020-2083-Z\/METRICS"},{"key":"e_1_2_11_25_1","volume-title":"IOP Conference Series: Materials Science and Engineering","author":"Akentieva N. P.","year":"2020"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/BIOMEDICINES6010006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/FPHAR.2022.888740\/BIBTEX"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2023.104371"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CPSURG.2024.101565"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFB.2011.09.042"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EURPOLYMJ.2022.111759"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CARBPOL.2021.118238"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFB.2005.06.001"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.TRAC.2013.06.002"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNANO.2022.1006628\/BIBTEX"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFB.2004.09.008"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1067\/MJD.2001.113476"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPB.2013.07.002"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJBIOMAC.2022.07.067"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573411018666220304085236"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJPHARM.2022.122580"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/1061186X.2022.2056188"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ENVRES.2023.116454"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ENVRES.2023.116562"},{"key":"e_1_2_11_45_1","unstructured":"IARC. n.d. \u201cSkin Cancer.\u201dhttps:\/\/www.iarc.who.int\/cancer-type\/skin-cancer\/."},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJPHARM.2021.121179"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPB.2021.04.007"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2025.107729"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.47750\/PNR.2022.13.S09.157"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2023.104164"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.30864"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CARPTA.2023.100293"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ADDR.2020.05.011"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11060-010-0389-0"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1634\/THEONCOLOGIST.7-4-288"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPS.2016.01.012"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFB.2021.112255"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/02652048.2018.1547325"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2019.1583205"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S165210"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S198353"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.DRUP.2022.100889"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2022.103447"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.4236\/JBNB.2012.34048"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.DRUDIS.2014.09.018"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ENVRES.2023.116850"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PRP.2025.156277"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JPHOTOBIOL.2017.05.028"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2020.101775"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOMATERIALS.2016.10.016"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1248\/BPB.B14-00535"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/ACS.MOLPHARMACEUT.8B00047"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFB.2018.11.018"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/S10350-006-0601-7"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJBIOMAC.2020.04.112"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.2217\/NNM-2020-0316"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.3109\/21691401.2015.1008502"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6009309"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLLIQ.2014.10.013"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.3109\/10717544.2013.868557"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1504\/IJNT.2019.107361"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCIS.2020.11.054"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JGR.2015.01.005"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CANLET.2014.11.001"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFB.2012.08.038"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJPHARM.2005.04.004"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDIN.2025.09.008"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1039\/C2NR32880A"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJBIOMAC.2017.08.057"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.3389\/FBIOE.2019.00415"},{"key":"e_1_2_11_91_1","unstructured":"Treatment For Cancer | Cancer Treatment Options | American Cancer Society. n.d.https:\/\/www.cancer.org\/cancer\/managing-cancer\/treatment-types.html."},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JSPS.2014.11.010"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPB.2008.01.025"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.COLSURFB.2013.04.045"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOMATERIALS.2013.03.008"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1021\/ACSAMI.5B01687"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1007\/S10904-019-01305-X\/METRICS"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0123461"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.APSB.2021.07.019"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2024.105825"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.3109\/09546630902789326"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.3390\/s22041364"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1080\/03639045.2020.1730398"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2020.102102"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2TA05984C"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70254","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ddr.70254","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70254","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T17:43:11Z","timestamp":1786038191000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,1]]},"references-count":104,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/ddr.70254"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70254","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,1]]},"assertion":[{"value":"2025-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70254"}}