{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:33:37Z","timestamp":1790800417689,"version":"4.1.0"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T00:00:00Z","timestamp":1429228800000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R44AI066442"],"award-info":[{"award-number":["R44AI066442"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tuberculosis (TB) remains a major global health concern, and new therapies are needed to overcome the problems associated with dosing frequency, patient compliance, and drug resistance. To reduce side effects associated with systemic drug distribution and improve drug concentration at the target site, stable therapeutic nanocarriers (NCs) were prepared and evaluated for efficacy in vitro in Mycobacterium tuberculosis-infected macrophages. Rifampicin (RIF), a current, broad-spectrum antibiotic used in TB therapy, was conjugated by degradable ester bonds to form hydrophobic prodrugs. NCs encapsulating various ratios of nonconjugated RIF and the prodrugs showed the potential ability to rapidly deliver and knockdown intracellular M. tuberculosis by nonconjugated RIF and to obtain sustained release of RIF by hydrolysis of the RIF prodrug. NCs of the novel antibiotic SQ641 and a combination NC with cyclosporine A were formed by flash nanoprecipitation. Delivery of SQ641 in NC form resulted in significantly improved activity compared to that of the free drug against intracellular M. tuberculosis. A NC formulation with a three-compound combination of SQ641, cyclosporine A, and vitamin E inhibited intracellular replication of M. tuberculosis significantly better than SQ641 alone or isoniazid, a current first-line anti-TB drug.<\/jats:p>","DOI":"10.1021\/mp5008663","type":"journal-article","created":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T10:32:28Z","timestamp":1427365948000},"page":"1554-1563","source":"Crossref","is-referenced-by-count":28,"title":["Antitubercular Nanocarrier Combination Therapy: Formulation\nStrategies and\n                    <i>in Vitro<\/i>\n                    Efficacy for Rifampicin and\nSQ641"],"prefix":"10.1021","volume":"12","author":[{"given":"Suzanne M.","family":"D\u2019Addio","sequence":"first","affiliation":[{"name":"Princeton University , , , ,","place":["Princeton, New Jersey, United States, 08544"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata M.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Sequella Inc. , , ,","place":["Rockville, Maryland, United States, 77845"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Princeton University , , , ,","place":["Princeton, New Jersey, United States, 08544"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Sinko","sequence":"additional","affiliation":[{"name":"Rutgers University , , , ,","place":["Piscataway, New Jersey, United States, 08854"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Einck","sequence":"additional","affiliation":[{"name":"Sequella Inc. , , ,","place":["Rockville, Maryland, United States, 77845"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert K.","family":"Prud\u2019homme","sequence":"additional","affiliation":[{"name":"Princeton University , , , ,","place":["Princeton, New Jersey, United States, 08544"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2015,3,26]]},"reference":[{"key":"2026090110001487500_cit1","unstructured":"Global Tuberculosis\nReport; World Health\nOrganization: Geneva, Switzerland, 2013."},{"key":"2026090110001487500_cit2","first-page":"437","article-title":"A comparison\nof rifampicin, ethambutol and PAS in short-term monotherapy. Preliminary\nresults of the third cooperative study of the WATL","volume":"60","author":"Schutz","year":"1969","journal-title":"Acta Tuberc. Pneumol. Belg."},{"key":"2026090110001487500_cit3","first-page":"939","article-title":"The early\nbactericidal activity of drugs in patients with pulmonary tuberculosis","volume":"121","author":"Jindani","year":"1980","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026090110001487500_cit4","first-page":"74","article-title":"Cavitary pulmonary tuberculosis:\nthe Holy Grail of disease transmission","volume":"86","author":"Yoder","year":"2004","journal-title":"Curr.\nSci."},{"key":"2026090110001487500_cit5","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1086\/318706","article-title":"A review\nof efficacy studies of 6-month short-course therapy for tuberculosis\namong patients infected with human immunodeficiency virus: differences\nin study outcomes","volume":"32","author":"El-Sadr","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"2026090110001487500_cit6","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.tube.2003.07.001","article-title":"Nanoparticle encapsulated\nantitubercular drugs as a potential oral drug delivery system against\nmurine tuberculosis","volume":"83","author":"Pandey","year":"2003","journal-title":"Tuberculosis"},{"key":"2026090110001487500_cit7","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1164\/rccm.200504-613PP","article-title":"The potential advantages\nof nanoparticle drug delivery systems in chemotherapy of tuberculosis","volume":"172","author":"Gelperina","year":"2005","journal-title":"Am. J. Resp. Crit. Care Med."},{"key":"2026090110001487500_cit8","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.addr.2007.11.006","article-title":"Targeted delivery of nanoparticles\nfor the treatment of lung diseases","volume":"60","author":"Azarmi","year":"2008","journal-title":"Adv. Drug\nDelivery Rev."},{"key":"2026090110001487500_cit9","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1164\/rccm.200206-626OC","article-title":"Incidence\nof serious side effects from first-line antituberculosis\ndrugs among patients treated for active tuberculosis","volume":"167","author":"Yee","year":"2003","journal-title":"Am. J. Resp. Crit. Care Med."},{"key":"2026090110001487500_cit10","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1517\/17425240903130577","article-title":"Fighting tuberculosis:\nold drugs, new formulations","volume":"6","author":"Blasi","year":"2009","journal-title":"Expert Opin. Drug\nDelivery"},{"key":"2026090110001487500_cit11","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature09657","article-title":"The challenge of new drug discovery\nfor tuberculosis","volume":"469","author":"Koul","year":"2011","journal-title":"Nature"},{"key":"2026090110001487500_cit12","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.2174\/092986709788186066","article-title":"New anti-tuberculosis\ndrugs: strategies,\nsources and new molecules","volume":"16","author":"Palomino","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"2026090110001487500_cit13","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/35095558","article-title":"How\ncan immunology contribute to the control of tuberculosis?","volume":"1","author":"Kaufmann","year":"2001","journal-title":"Nat. Rev. Immunol."},{"key":"2026090110001487500_cit14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1023\/A:1010061013365","article-title":"Nanoparticles as\nantituberculosis drugs carriers: effect on activity against Mycobacterium tuberculosis in human monocyte-derived macrophages","volume":"2","author":"Anisimova","year":"2000","journal-title":"J. Nanopart. Res."},{"key":"2026090110001487500_cit15","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1007\/s11095-009-9957-4","article-title":"Inhaled drug delivery for tuberculosis\ntherapy","volume":"26","author":"Muttil","year":"2009","journal-title":"Pharm. 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M.; Bogatcheva, E.; Protopopova, M.\n          Enhancement\nof Intracellular\nActivity of Capuramycin (CM) Analogue SQ641 against M. tuberculosis\n(MTB), abstract C1-3851, 48th Interscience Conference\non Antimicrobial Agents and Chemotherapy, Washington,\nDC, October 24\u201328, 2008."},{"key":"2026090110001487500_cit20","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1128\/AAC.01469-07","article-title":"In vitro\nantimycobacterial activities\nof capuramycin analogues","volume":"52","author":"Reddy","year":"2008","journal-title":"Antimicrob. Agents\nChemother."},{"key":"2026090110001487500_cit21","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1128\/AAC.00366-09","article-title":"Activity\nof SQ641, a capuramycin\nanalog, in a murine model of tuberculosis","volume":"53","author":"Nikonenko","year":"2009","journal-title":"Antimicrob.\nAgents Chemother."},{"key":"2026090110001487500_cit22","doi-asserted-by":"crossref","first-page":"7132","DOI":"10.1021\/ma201169z","article-title":"A strategy\nfor control of \u201crandom\u201dcopolymerization of lactide and\nglycolide: application to synthesis of PEG-b-PLGA\nblock polymers having narrow dispersity","volume":"44","author":"Qian","year":"2011","journal-title":"Macromolecules"},{"key":"2026090110001487500_cit23","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1039\/C0PY00350F","article-title":"Photocrosslinking\nthe polystyrene core of block-copolymer nanoparticles","volume":"2","author":"Zhang","year":"2011","journal-title":"Polym. Chem."},{"key":"2026090110001487500_cit24","doi-asserted-by":"crossref","first-page":"4018","DOI":"10.1002\/jps.23259","article-title":"A simple confined impingement jets mixer for flash\nnanoprecipitation","volume":"10","author":"Han","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"2026090110001487500_cit25","unstructured":"Johnson, B. K.; Prud\u2019homme, R. K.\n          Engineering\nthe Direct Precipitation\nof Stabilized Organic and Block Copolymer Nanoparticles as Unique\nComposites, The 226th ACS National Meeting, New York, NY, September 7\u201311, 2003."},{"key":"2026090110001487500_cit26","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1016\/j.ces.2007.10.020","article-title":"Mixing in a multi-inlet vortex mixer\n(MIVM) for flash\nnano-precipitation","volume":"63","author":"Liu","year":"2008","journal-title":"Chem. Eng. 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Chem."},{"key":"2026090110001487500_cit34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.addr.2011.04.005","article-title":"Controlling drug nanoparticle\nformation by rapid precipitation","volume":"63","author":"D\u2019Addio","year":"2011","journal-title":"Adv. Drug\nDelivery Rev."},{"key":"2026090110001487500_cit35","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0022-0248(94)90468-5","article-title":"Nucleation\nand growth kinetics of biochemicals measured\nat high supersaturations","volume":"144","author":"Mahajan","year":"1994","journal-title":"J. Cryst. Growth"},{"key":"2026090110001487500_cit36","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/adfm.200801583","article-title":"Generic\nmethod of preparing multifunctional fluorescent nanoparticles using\nflash nanoprecipitation","volume":"19","author":"Akbulut","year":"2009","journal-title":"Adv. Funct. Mater."},{"key":"2026090110001487500_cit37","doi-asserted-by":"crossref","first-page":"11613","DOI":"10.1073\/pnas.0801763105","article-title":"The effect\nof particle design on\ncellular internalization pathways","volume":"105","author":"Gratton","year":"2008","journal-title":"Proc. Natl.\nAcad. Sci. U.S.A."},{"key":"2026090110001487500_cit38","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1021\/mp900245h","article-title":"Stabilization\nof the nitric oxide (NO) prodrugs and anticancer leads, PABA\/NO and\ndouble JS-K, through incorporation into PEG-protected nanoparticles","volume":"7","author":"Kumar","year":"2010","journal-title":"Mol. Pharmaceutics"},{"key":"2026090110001487500_cit39","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.jct.2009.06.014","article-title":"Volumetric properties of the (tetrahydrofuran\nplus water) and (tetra-n-butyl ammonium bromide plus water) systems:\nExperimental measurements and correlations","volume":"41","author":"Belandria","year":"2009","journal-title":"J. Chem. Thermodyn."},{"key":"2026090110001487500_cit40","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/syn.20348","article-title":"Effect of a P-glycoprotein\ninhibitor, cyclosporin A, on the disposition in rodent brain and blood\nof the 5-HT1A receptor radioligand, [C-11](R)-(\u2212)-RWAY","volume":"61","author":"Liow","year":"2007","journal-title":"Synapse"},{"key":"2026090110001487500_cit41","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1093\/jac\/dkl500","article-title":"Enhanced killing of intracellular\nmultidrug-resistant Mycobacterium tuberculosis by\ncompounds that affect the activity of efflux pumps","volume":"59","author":"Amaral","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090110001487500_cit42","doi-asserted-by":"crossref","first-page":"5314","DOI":"10.1128\/IAI.66.11.5314-5321.1998","article-title":"1,25-Dihydroxyvitamin D-3 induces nitric oxide synthase\nand suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line","volume":"66","author":"Rockett","year":"1998","journal-title":"Infect.\nImmun."},{"key":"2026090110001487500_cit43","unstructured":"Wohl, A. R.; Han, J.; Guru, B. R.; Panyam, J.; Hoye, T. R.; Macosko, C. W. In  Silicate Prodrug-Loaded Nanoparticles, AIChE Annual Meeting, Minneapolis,\nMN, October 16\u201321, 2011."}],"container-title":["Molecular Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/mp5008663","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/12\/5\/1554\/14376341\/mp5008663.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/12\/5\/1554\/14376341\/mp5008663.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:00:26Z","timestamp":1788271226000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article\/12\/5\/1554\/1379867\/Antitubercular-Nanocarrier-Combination-Therapy"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,26]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,3,26]]},"published-print":{"date-parts":[[2015,5,4]]}},"URL":"https:\/\/doi.org\/10.1021\/mp5008663","relation":{},"ISSN":["1543-8384","1543-8392"],"issn-type":[{"value":"1543-8384","type":"print"},{"value":"1543-8392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,26]]}}}