{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:31:04Z","timestamp":1793723464934,"version":"4.6.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1007\/s13346-018-0532-6","type":"journal-article","created":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T13:26:49Z","timestamp":1525181209000},"page":"1066-1077","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers\u2014in vitro and in vivo studies"],"prefix":"10.1007","volume":"8","author":[{"given":"K.","family":"Madhumathi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Rubaiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukesh","family":"Doble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Venkateswari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. S.","family":"Sampath Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,1]]},"reference":[{"key":"532_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.progsolidstchem.2012.05.001","volume":"40","author":"M Manzano","year":"2012","unstructured":"Manzano M, Regi MV. Revisiting bioceramics: bone regenerative and local drug delivery systems. Prog Solid State Chem. 2012;40:17\u201330.","journal-title":"Prog Solid State Chem"},{"key":"532_CR2","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.ejpb.2013.11.001","volume":"87","author":"G D\u2019Arrigo","year":"2014","unstructured":"D\u2019Arrigo G, Navarro G, Meo CD, Matricardi P, Torchilin V. Gellan gum nanohydrogel containing anti-inflammatory and anti-cancer drugs: a multi-drug delivery system for a combination therapy in cancer treatment. Eur J Pharm Biopharm. 2014;87:208\u201316.","journal-title":"Eur J Pharm Biopharm"},{"key":"532_CR3","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s11095-010-0308-2","volume":"28","author":"Z Wang","year":"2011","unstructured":"Wang Z, Chui W-K, Ho PC. Nanoparticulate delivery system targeted to tumor neovasculature for combined anticancer and antiangiogenesis therapy. Pharm Res. 2011;28:585\u201396.","journal-title":"Pharm Res"},{"key":"532_CR4","doi-asserted-by":"publisher","first-page":"6086","DOI":"10.1016\/j.biomaterials.2009.07.045","volume":"30","author":"SH Lepretre","year":"2009","unstructured":"Lepretre SH, Chai F, Hornez JC, Vermet G, Neut C, Descamps M, et al. Prolonged local antibiotics delivery from hydroxyapatite functionalised with cyclodextrin polymers. Biomaterials. 2009;30:6086\u201393.","journal-title":"Biomaterials"},{"key":"532_CR5","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.injury.2014.11.014","volume":"46","author":"PP Arias","year":"2015","unstructured":"Arias PP, Tafin UF, Betrisey B, Vogt S, Trampuz A, Borens O. Activity of bone cement loaded with daptomycin alone or in combination with gentamicin or PEG600 against Staphylococcus epidermidis biofilms. Injury. 2015;46:249\u201353.","journal-title":"Injury"},{"key":"532_CR6","doi-asserted-by":"publisher","first-page":"8835","DOI":"10.1016\/j.biomaterials.2013.07.093","volume":"34","author":"SC Sundararaj","year":"2013","unstructured":"Sundararaj SC, Thomas MV, Peyyala R, Dziubla TD, Puleo DA. Design of a multiple drug delivery system directed at periodontitis. Biomaterials. 2013;34:8835\u201342.","journal-title":"Biomaterials"},{"key":"532_CR7","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1016\/j.actbio.2012.06.022","volume":"8","author":"E Verron","year":"2012","unstructured":"Verron E, Bouler JM, Guicheux J. Controlling the biological function of calcium phosphate bone substitutes with drugs. Acta Biomater. 2012;8:3541\u201351.","journal-title":"Acta Biomater"},{"key":"532_CR8","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1016\/S0140-6736(05)67728-8","volume":"366","author":"BL Philstrom","year":"2005","unstructured":"Philstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366:1809\u201320.","journal-title":"Lancet"},{"key":"532_CR9","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1902\/jop.2015.140520","volume":"86","author":"PI Eke","year":"2015","unstructured":"Eke PI, Dye BA, Wei L, Slade GD, Thornton-Evans GO, Borgnakke WS, et al. Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015;86:611\u201322.","journal-title":"J Periodontol"},{"key":"532_CR10","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/j.1600-0757.2004.03677.x","volume":"36","author":"CB Walker","year":"2004","unstructured":"Walker CB, Karpinia K, Baehni P. Chemotherapeutics: antibiotics and other antimicrobials. Periodontol. 2004;36:146\u201365.","journal-title":"Periodontol"},{"key":"532_CR11","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1111\/j.1600-051X.2008.01239.x","volume":"35","author":"J Eberhard","year":"2008","unstructured":"Eberhard J, Jervoe-Storm PM, Needleman I, Worthington H, Jepsen S. Full-mouth treatment concepts for chronic periodontitis: a systematic review. J Clin Periodontol. 2008;35:591\u2013604.","journal-title":"J Clin Periodontol"},{"key":"532_CR12","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1034\/j.1600-051x.2000.027001053.x","volume":"27","author":"D Sakellari","year":"2000","unstructured":"Sakellari D, Goodson JK, Socransky SS, Kolokotronis A, Konstantinidis A. Concentration of 3 tetracyclines in plasma, gingival crevicular fluid and saliva. J Clin Periodontol. 2000;27:53\u201360.","journal-title":"J Clin Periodontol"},{"key":"532_CR13","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1902\/jop.1998.69.10.1085","volume":"69","author":"NH Stoller","year":"1998","unstructured":"Stoller NH, Johnson LR, Trapnell S, Harrold CQ, Garrett S. The pharmacokinetic profile of a biodegradable controlled-release delivery system containing doxycycline compared to systemically delivered doxycycline in gingival crevicular fluid, saliva, and serum. J Periodontol. 1998;69:1085\u201391.","journal-title":"J Periodontol"},{"key":"532_CR14","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.jaad.2005.10.004","volume":"54","author":"AN Sapadin","year":"2006","unstructured":"Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Amer Acad Derm. 2006;54:258\u201365.","journal-title":"J Amer Acad Derm"},{"key":"532_CR15","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.phrs.2010.10.006","volume":"63","author":"JB Payne","year":"2011","unstructured":"Payne JB, Golub LM. Using tetracyclines to treat osteoporotic\/osteopenic bone loss: from the basic science laboratory to the clinic. Pharm Res. 2011;63:121\u20139.","journal-title":"Pharm Res"},{"key":"532_CR16","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1007\/BF02405117","volume":"35","author":"HM Myers","year":"1983","unstructured":"Myers HM, Tochon-Danguy HJ, Baud CA. IR absorption spectrophotometric analysis of the complex formed by tetracycline and synthetic hydroxyapatite. Calcif Tissue Int. 1983;35:745\u20139.","journal-title":"Calcif Tissue Int"},{"key":"532_CR17","doi-asserted-by":"publisher","first-page":"035002","DOI":"10.1088\/1748-6041\/9\/3\/035002","volume":"9","author":"K Madhumathi","year":"2014","unstructured":"Madhumathi K, Sampath Kumar TS. Regenerative potential and anti-bacterial activity of tetracycline loaded apatitic nanocarriers for the treatment of periodontitis. Biomed Mater. 2014;9:035002.","journal-title":"Biomed Mater"},{"key":"532_CR18","first-page":"203","volume":"4","author":"SP Victor","year":"2008","unstructured":"Victor SP, Sampath Kumar TS. Tailoring calcium-deficient hydroxyapatite nanocarriers for enhanced release of antibiotics. J Biomed Nanotech. 2008;4:203\u20139.","journal-title":"J Biomed Nanotech"},{"key":"532_CR19","doi-asserted-by":"publisher","first-page":"495","DOI":"10.4028\/www.scientific.net\/KEM.529-530.495","volume":"529-530","author":"K Madhumathi","year":"2013","unstructured":"Madhumathi K, Sampath Kumar TS. Effect of structure and composition on ibuprofen drug delivery by calcium phosphate nanocarriers. Key Eng Mater. 2013;529-530:495\u2013500.","journal-title":"Key Eng Mater"},{"key":"532_CR20","first-page":"189","volume":"3","author":"G Leelaprakash","year":"2011","unstructured":"Leelaprakash G, Mohan DS. In vitro anti-inflammatory activity of methanol extract of enicostemma axillare. Int J Drug Dev Res. 2011;3:189\u201396.","journal-title":"Int J Drug Dev Res"},{"key":"532_CR21","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1002\/jbm.b.30692","volume":"81B","author":"QQ Qiu","year":"2007","unstructured":"Qiu QQ, Mendenhall HV, Garlick DS, Connor J. Evaluation of bone regeneration at critical-sized calvarial defect by DBM\/AM composite. J Biomed Mater Res Part B: Appl Biomater. 2007;81B:516\u201323.","journal-title":"J Biomed Mater Res Part B: Appl Biomater"},{"key":"532_CR22","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/S0928-0987(01)00095-1","volume":"13","author":"P Costa","year":"2001","unstructured":"Costa P, Lobo J-MS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13:123\u201333.","journal-title":"Eur J Pharm Sci"},{"key":"532_CR23","doi-asserted-by":"publisher","first-page":"9031","DOI":"10.1016\/j.biomaterials.2011.08.032","volume":"32","author":"F Chen","year":"2011","unstructured":"Chen F, Huang P, Zhu YZ, Wu J, Zhang CL, Cui DX. The photoluminescence, drug delivery and imaging properties of multifunctional Eu3+\/Gd3+ dual-doped hydroxyapatite nanorods. Biomaterials. 2011;32:9031\u20139.","journal-title":"Biomaterials"},{"key":"532_CR24","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ijpharm.2015.03.048","volume":"486","author":"JL Paris","year":"2015","unstructured":"Paris JL, Roman J, Manzano M, Cabanas MV, Vallet-Regi M. Tuning dual-drug release from composite scaffolds for bone regeneration. Int J Pharm. 2015;486:30\u20137.","journal-title":"Int J Pharm"},{"key":"532_CR25","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1093\/jac\/dkn079","volume":"61","author":"EM Kulik","year":"2008","unstructured":"Kulik EM, Lenkeit K, Chenaux S, Meyer J. Antimicrobial susceptibility of periodontopathogenic bacteria. J Antimicrob Chemother. 2008;61:1087\u201391.","journal-title":"J Antimicrob Chemother"},{"key":"532_CR26","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1128\/AAC.42.11.3022","volume":"42","author":"MT Andr\u00e9s","year":"1998","unstructured":"Andr\u00e9s MT, Chung WO, Roberts MC, Fierro JF. Antimicrobial susceptibilities of Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens spp. isolated in Spain. Antimicrob Agents Chemother. 1998;42:3022\u20133.","journal-title":"Antimicrob Agents Chemother"},{"key":"532_CR27","doi-asserted-by":"publisher","first-page":"20320","DOI":"10.3402\/jom.v5i0.20320","volume":"5","author":"O Oettinger-Barak","year":"2013","unstructured":"Oettinger-Barak O, Dashper SG, Catmull DV, Adams GG, Sela MN, Machtei EE, et al. Antibiotic susceptibility of Aggregatibacter actinomycetemcomitans JP2 in a biofilm. J Oral Microb. 2013;5:20320.","journal-title":"J Oral Microb"},{"key":"532_CR28","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1007\/BF02976483","volume":"24","author":"L Saso","year":"2001","unstructured":"Saso L, Valentini G, Casini ML, Grippa E, Gatto MT, Leone MG, et al. Inhibition of heat-induced denaturation of albumin by nonsteroidal anti-inflammatory drugs (NSAIDs): pharmacological implications. Arch Pharm Res. 2001;24:150\u20138.","journal-title":"Arch Pharm Res"},{"key":"532_CR29","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/1471-2474-7-50","volume":"7","author":"FX Huber","year":"2006","unstructured":"Huber FX, Belyaev O, Hillmeier J, Kock H-J, Huber C, Meeder PJ, et al. First histological observations on the incorporation of a novel nanocrystalline hydroxyapatite paste OSTIM\u00ae in human cancellous bone. BMC Musculoskelet Disord. 2006;7:50\u201364.","journal-title":"BMC Musculoskelet Disord"},{"key":"532_CR30","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1016\/j.transproceed.2008.07.096","volume":"40","author":"H Sun","year":"2008","unstructured":"Sun H, Ye F, Wang J, Shi Y, Tu Z, Bao J, et al. The upregulation of osteoblast marker genes in mesenchymal stem cells prove the osteoinductivity of hydroxyapatite\/tricalcium phosphate biomaterial. Transplant Proc. 2008;40:2645\u20138.","journal-title":"Transplant Proc"}],"container-title":["Drug Delivery and Translational Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s13346-018-0532-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-018-0532-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-018-0532-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T20:16:01Z","timestamp":1556655361000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s13346-018-0532-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,1]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["532"],"URL":"https:\/\/doi.org\/10.1007\/s13346-018-0532-6","relation":{},"ISSN":["2190-393X","2190-3948"],"issn-type":[{"value":"2190-393X","type":"print"},{"value":"2190-3948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,1]]},"assertion":[{"value":"1 May 2018","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All institutional and national guidelines for the care and use of laboratory animals were followed.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement on the welfare of animals"}}]}}