{"id":"https://openalex.org/W7202170258","doi":"https://doi.org/10.1038/s41524-026-02262-z","title":"Physics-informed design of drug-excipient nanoparticles via free energy calculation and yoked deep learning","display_name":"Physics-informed design of drug-excipient nanoparticles via free energy calculation and yoked deep learning","publication_year":2026,"publication_date":"2026-08-11","ids":{"openalex":"https://openalex.org/W7202170258","doi":"https://doi.org/10.1038/s41524-026-02262-z"},"language":"en","primary_location":{"id":"doi:10.1038/s41524-026-02262-z","doi":"https://doi.org/10.1038/s41524-026-02262-z","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41524-026-02262-z","pdf_url":"https://www.nature.com/articles/s41524-026-02262-z_reference.pdf","source":{"id":"https://openalex.org/S4210232664","display_name":"npj Computational Materials","issn_l":"2057-3960","issn":["2057-3960"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-a","jufo-1","norway-1","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"npj Computational Materials","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.nature.com/articles/s41524-026-02262-z_reference.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5125243829","display_name":"Yan Xiang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yan Xiang","raw_affiliation_strings":["Department of Biomedical Engineering, Duke University, Durham, NC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biomedical Engineering, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5133006262","display_name":"Zilu Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Zilu Zhang","raw_affiliation_strings":["Department of Biomedical Engineering, Duke University, Durham, NC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biomedical Engineering, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046277450","display_name":"Rebeca T. Stiepel","orcid":"https://orcid.org/0000-0001-6943-8818","observed_orcids":["https://orcid.org/0000-0001-6943-8818"]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rebeca T. Stiepel","raw_affiliation_strings":["Department of Biomedical Engineering, Duke University, Durham, NC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biomedical Engineering, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022579350","display_name":"Chinmay S. Potnis","orcid":"https://orcid.org/0000-0002-6953-9106","observed_orcids":["https://orcid.org/0000-0002-6953-9106"]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Chinmay S. Potnis","raw_affiliation_strings":["Department of Biomedical Engineering, Duke University, Durham, NC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biomedical Engineering, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5092414875","display_name":"Lauren A. Onweller","orcid":"https://orcid.org/0009-0004-0865-4495","observed_orcids":["https://orcid.org/0009-0004-0865-4495"]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lauren A. Onweller","raw_affiliation_strings":["Department of Biomedical Engineering, Duke University, Durham, NC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biomedical Engineering, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068391488","display_name":"Joseph Laforet","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joseph R. Laforet","raw_affiliation_strings":["Department of Biomedical Engineering, Duke University, Durham, NC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biomedical Engineering, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5146481599","display_name":"Hrshita Gowda","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hrshita Gowda","raw_affiliation_strings":["Department of Biomedical Engineering, Duke University, Durham, NC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biomedical Engineering, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5020392456","display_name":"Daniel Reker","orcid":"https://orcid.org/0000-0003-4789-7380","observed_orcids":["https://orcid.org/0000-0003-4789-7380"]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]},{"id":"https://openalex.org/I4390039326","display_name":"Duke Cancer Institute","ror":"https://ror.org/04vt65461","country_code":null,"type":"healthcare","lineage":["https://openalex.org/I4210126298","https://openalex.org/I4210144876","https://openalex.org/I4390039326"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Daniel Reker","raw_affiliation_strings":["Center for Quantitative Biodesign, Duke University, Durham, NC, USA","Department of Biomedical Engineering, Duke University, Durham, NC, USA","Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Quantitative Biodesign, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]},{"raw_affiliation_string":"Department of Biomedical Engineering, Duke University, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317"]},{"raw_affiliation_string":"Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA","institution_ids":["https://openalex.org/I170897317","https://openalex.org/I4390039326"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5020392456"],"corresponding_institution_ids":["https://openalex.org/I170897317","https://openalex.org/I4390039326"],"apc_list":{"value":3490,"currency":"USD","value_usd":3490},"apc_paid":{"value":3490,"currency":"USD","value_usd":3490},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.50696847,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11948","display_name":"Machine Learning in Materials Science","score":0.5062999725341797,"subfield":{"id":"https://openalex.org/subfields/2505","display_name":"Materials Chemistry"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11948","display_name":"Machine Learning in Materials Science","score":0.5062999725341797,"subfield":{"id":"https://openalex.org/subfields/2505","display_name":"Materials Chemistry"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.4372999966144562,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10063","display_name":"Nanoparticle-Based Drug Delivery","score":0.01759999990463257,"subfield":{"id":"https://openalex.org/subfields/2502","display_name":"Biomaterials"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/nanoparticle-self-assembly","display_name":"nanoparticle self-assembly","score":0.7509999871253967},{"id":"https://openalex.org/keywords/free-energy-calculations","display_name":"free energy calculation","score":0.6840000152587891},{"id":"https://openalex.org/keywords/physics-informed-machine-learning","display_name":"physics-informed machine learning","score":0.8029999732971191},{"id":"https://openalex.org/keywords/interfacial-stabilization","display_name":"interfacial stabilization","score":0.9490000009536743},{"id":"https://openalex.org/keywords/drug-solubility-enhancement","display_name":"drug solubility enhancement","score":0.6660000085830688},{"id":"https://openalex.org/keywords/sorafenib","display_name":"sorafenib","score":0.9369999766349792},{"id":"https://openalex.org/keywords/poorly-water-soluble-drugs","display_name":"poorly water-soluble drugs","score":0.7609999775886536},{"id":"https://openalex.org/keywords/nanoparticle-formulation","display_name":"nanoparticle formulation","score":0.46000000834465027}],"concepts":[{"id":"https://openalex.org/C108583219","wikidata":"https://www.wikidata.org/wiki/Q197536","display_name":"Deep learning","level":2,"score":0.7045999765396118},{"id":"https://openalex.org/C27158222","wikidata":"https://www.wikidata.org/wiki/Q5532422","display_name":"Generalizability theory","level":2,"score":0.6276000142097473},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.6057999730110168},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5845999717712402},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.4465000033378601},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.40389999747276306},{"id":"https://openalex.org/C184898388","wikidata":"https://www.wikidata.org/wiki/Q1435712","display_name":"Pairwise comparison","level":2,"score":0.3993000090122223},{"id":"https://openalex.org/C131584629","wikidata":"https://www.wikidata.org/wiki/Q4308705","display_name":"Coupling (piping)","level":2,"score":0.3635999858379364},{"id":"https://openalex.org/C171250308","wikidata":"https://www.wikidata.org/wiki/Q11468","display_name":"Nanotechnology","level":1,"score":0.3366999924182892},{"id":"https://openalex.org/C66024118","wikidata":"https://www.wikidata.org/wiki/Q1122506","display_name":"Computational model","level":2,"score":0.32670000195503235},{"id":"https://openalex.org/C155672457","wikidata":"https://www.wikidata.org/wiki/Q61231","display_name":"Nanoparticle","level":2,"score":0.32179999351501465},{"id":"https://openalex.org/C186370098","wikidata":"https://www.wikidata.org/wiki/Q442787","display_name":"Energy (signal processing)","level":2,"score":0.3100000023841858},{"id":"https://openalex.org/C183696295","wikidata":"https://www.wikidata.org/wiki/Q2487696","display_name":"Biochemical engineering","level":1,"score":0.30649998784065247},{"id":"https://openalex.org/C164923092","wikidata":"https://www.wikidata.org/wiki/Q3705921","display_name":"Molecular descriptor","level":3,"score":0.30469998717308044},{"id":"https://openalex.org/C2777239854","wikidata":"https://www.wikidata.org/wiki/Q902638","display_name":"Excipient","level":2,"score":0.3028999865055084},{"id":"https://openalex.org/C63479239","wikidata":"https://www.wikidata.org/wiki/Q7353546","display_name":"Robustness (evolution)","level":3,"score":0.2802000045776367},{"id":"https://openalex.org/C177774035","wikidata":"https://www.wikidata.org/wiki/Q1246948","display_name":"Granularity","level":2,"score":0.2734000086784363},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.2718000113964081},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.2596000134944916},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.25429999828338623},{"id":"https://openalex.org/C77967617","wikidata":"https://www.wikidata.org/wiki/Q4677561","display_name":"Active learning (machine learning)","level":2,"score":0.2529999911785126},{"id":"https://openalex.org/C18762648","wikidata":"https://www.wikidata.org/wiki/Q42213","display_name":"Work (physics)","level":2,"score":0.25220000743865967},{"id":"https://openalex.org/C48044578","wikidata":"https://www.wikidata.org/wiki/Q727490","display_name":"Scalability","level":2,"score":0.2517000138759613}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1038/s41524-026-02262-z","doi":"https://doi.org/10.1038/s41524-026-02262-z","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41524-026-02262-z","pdf_url":"https://www.nature.com/articles/s41524-026-02262-z_reference.pdf","source":{"id":"https://openalex.org/S4210232664","display_name":"npj Computational Materials","issn_l":"2057-3960","issn":["2057-3960"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-a","jufo-1","norway-1","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"npj Computational Materials","raw_type":"journal-article"},{"id":"doi:10.26434/chemrxiv.15001656/v1","doi":"https://doi.org/10.26434/chemrxiv.15001656/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15001656/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15001656/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1038/s41524-026-02262-z","doi":"https://doi.org/10.1038/s41524-026-02262-z","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41524-026-02262-z","pdf_url":"https://www.nature.com/articles/s41524-026-02262-z_reference.pdf","source":{"id":"https://openalex.org/S4210232664","display_name":"npj Computational Materials","issn_l":"2057-3960","issn":["2057-3960"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-a","jufo-1","norway-1","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"npj Computational Materials","raw_type":"journal-article"},"sustainable_development_goals":[],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/7","display_name":"Affordable and clean energy","score":0.7148679494857788}],"study_designs":[],"awards":[{"id":"https://openalex.org/G123281693","display_name":null,"funder_award_id":"5R35GM151255","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G1638877007","display_name":"NNCI: North Carolina Research Triangle Nanotechnology Network (RTNN)","funder_award_id":"2025064","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G1676019983","display_name":null,"funder_award_id":"2025064","funder_id":"https://openalex.org/F4320337392","funder_display_name":"Division of Electrical, Communications and Cyber Systems"},{"id":"https://openalex.org/G5973914729","display_name":null,"funder_award_id":"ECCS\u20102025064","funder_id":"https://openalex.org/F4320337392","funder_display_name":"Division of Electrical, Communications and Cyber Systems"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"},{"id":"https://openalex.org/F4320337392","display_name":"Division of Electrical, Communications and Cyber Systems","ror":"https://ror.org/01krpsy48"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7202170258.pdf","grobid_xml":"https://content.openalex.org/works/W7202170258.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"The":[0,142],"discovery":[1,43,178],"of":[2,14,21,74,115,125,154],"self-assembling":[3,180],"molecular":[4,128,170,181],"systems":[5],"is":[6],"often":[7],"constrained":[8],"by":[9],"the":[10,18,113,151],"high":[11],"computational":[12],"cost":[13],"physics-based":[15],"simulations":[16,117,171],"and":[17,53,77,156,172],"limited":[19],"generalizability":[20],"data-driven":[22],"models":[23],"trained":[24],"on":[25,95],"experimental":[26,96],"datasets.":[27],"This":[28],"limits":[29],"our":[30,87],"ability":[31],"to":[32,58,111,176],"efficiently":[33],"navigate":[34,60],"massive":[35],"design":[36],"spaces.":[37,64],"Here,":[38],"we":[39],"introduce":[40],"a":[41,70,82,166],"physics-informed":[42],"framework":[44,168],"that":[45],"integrates":[46],"free-energy":[47],"calculations":[48],"with":[49],"sequential-pool":[50,102],"active":[51],"learning":[52,57,105,110,175],"adaptive":[54,108],"yoked":[55,103,173],"deep":[56,104,174],"effectively":[59,149],"vast":[61],"chemical":[62],"coassembly":[63],"Using":[65],"pairwise":[66],"free":[67],"energy":[68],"as":[69,81],"physically":[71],"grounded":[72],"descriptor":[73],"co-assembly":[75],"propensity":[76],"excipient":[78],"net":[79],"charge":[80],"proxy":[83],"for":[84,98],"interfacial":[85],"stabilization,":[86],"approach":[88],"predicts":[89],"nanoparticle-forming":[90],"drug\u2013excipient":[91],"combinations":[92],"without":[93],"relying":[94],"data":[97],"model":[99],"training.":[100],"Our":[101],"strategy":[106],"utilizes":[107],"machine":[109],"reduce":[112],"number":[114],"expensive":[116],"required":[118],"while":[119],"maintaining":[120],"predictive":[121],"accuracy,":[122],"enabling":[123],"screening":[124],"18":[126],"million":[127],"pairs.":[129],"Prospective":[130],"validations":[131],"identified":[132],"24":[133],"drug":[134,147,160],"nanoparticles":[135,144],"using":[136],"eight":[137],"previously":[138],"unknown":[139],"stabilizing":[140],"molecules.":[141],"new":[143],"exhibit":[145],"ultra-high":[146],"loading,":[148],"improve":[150],"aqueous":[152],"solubility":[153],"drugs,":[155],"maintain":[157],"in":[158,179],"vitro":[159],"efficacy.":[161],"Together,":[162],"this":[163],"work":[164],"establishes":[165],"generalizable":[167],"coupling":[169],"accelerate":[177],"systems.":[182]},"counts_by_year":[],"updated_date":"2026-10-09T09:14:12.587421","created_date":"2026-08-12T00:00:00"}