{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:12:55Z","timestamp":1793722375896,"version":"4.6.1"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001408","name":"Department of Scientific and Industrial Research, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["ECR\/2016\/000977"],"award-info":[{"award-number":["ECR\/2016\/000977"]}],"id":[{"id":"10.13039\/501100001408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The development of an effective oral therapeutics is an immediate need for the control and elimination of visceral leishmaniasis (VL). We exemplify the preparation and optimization of 2-hydroxypropyl-\u03b2-cyclodextrin (HPCD) modified solid lipid nanoparticles (SLNs) based oral combinational cargo system of Amphotericin B (AmB) and Paromomycin (PM) against murine VL. The emulsion solvent evaporation method was employed to prepare HPCD modified dual drug-loaded solid lipid nanoparticles (m-DDSLNs). The optimized formulations have a mean particle size of 141\u2009\u00b1\u20093.2\u00a0nm, a polydispersity index of 0.248\u2009\u00b1\u20090.11 and entrapment efficiency for AmB and PM was found to be 96% and 90% respectively. The morphology of m-DDSLNs was confirmed by scanning electron microscopy and transmission electron microscopy. The developed formulations revealed a sustained drug release profile upto 57% (AmB) and 21.5% (PM) within 72\u00a0h and were stable at both 4\u00a0\u00b0C and 25\u00a0\u00b0C during short term stability studies performed for 2\u00a0months. Confocal laser scanning microscopy confirmed complete cellular internalization of SLNs within 24\u00a0h of incubation. In vitro cytotoxicity study against J774A.1 macrophage cells confirmed the safety and biocompatibility of the developed formulations. Further, m-DDSLNs did not induce any hepatic\/renal toxicities in Swiss albino mice. The in vitro simulated study was performed to check the stability in simulated gastric fluids and simulated intestinal fluids and the release was found almost negligible. The in vitro anti-leishmanial activity of m-DDSLNs (1\u00a0\u00b5g\/ml) has shown a maximum percentage of inhibition (96.22%) on intra-cellular amastigote growth of\n                    <jats:italic>L. donovani<\/jats:italic>\n                    . m-DDSLNs (20\u00a0mg\/kg\u2009\u00d7\u20095\u00a0days,\n                    <jats:italic>p.o.<\/jats:italic>\n                    ) has significantly (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01) reduced the liver parasite burden as compared to miltefosine (3\u00a0mg\/kg\u2009\u00d7\u20095\u00a0days,\n                    <jats:italic>p.o.<\/jats:italic>\n                    ) in\n                    <jats:italic>L. donovani<\/jats:italic>\n                    -infected BALB\/c mice. This work suggests that the superiority of as-prepared m-DDSLNs as a promising approach towards the oral delivery of anti-leishmanial drugs.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-69276-5","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T06:07:35Z","timestamp":1595398055000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis"],"prefix":"10.1038","volume":"10","author":[{"given":"Shabi","family":"Parvez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Yadagiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallikarjuna Rao","family":"Gedda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakriti","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Om Prakash","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Sundar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam Lal","family":"Mudavath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,22]]},"reference":[{"key":"69276_CR1","doi-asserted-by":"crossref","unstructured":"Yadagiri, G. & Singh, P. P. Chemotherapy and experimental models of visceral leishmaniasis. in Infectious Diseases and Your Health 63\u201397 (2018).","DOI":"10.1007\/978-981-13-1577-0_5"},{"key":"69276_CR2","unstructured":"https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis. Leishmaniasis. 1\u20135 (2019). Accessed 5 June 2019."},{"key":"69276_CR3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4103\/2229-5070.162487","volume":"5","author":"S Sundar","year":"2015","unstructured":"Sundar, S. Visceral leishmaniasis. Trop. Parasitol. 5, 83\u201385 (2015).","journal-title":"Trop. Parasitol."},{"key":"69276_CR4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pntd.0007616","volume":"13","author":"A Selvapandiyan","year":"2019","unstructured":"Selvapandiyan, A., Croft, S. L., Rijal, S., Nakhasi, H. L. & Ganguly, N. K. Innovations for the elimination and control of visceral leishmaniasis. PLoS Negl. Trop. Dis. 13, 1\u20135 (2019).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"69276_CR5","first-page":"9","volume":"1","author":"L Monzote","year":"2009","unstructured":"Monzote, L. Current treatment of leishmaniasis: a review. Open Antimicrob. Agents J. 1, 9\u201319 (2009).","journal-title":"Open Antimicrob. Agents J."},{"key":"69276_CR6","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/1389557517666170425105129","volume":"18","author":"N Tiwari","year":"2017","unstructured":"Tiwari, N., Gedda, M. R., Tiwari, V. K., Singh, S. P. & Singh, R. K. Limitations of current therapeutic options, possible drug targets and scope of natural products in control of leishmaniasis. Mini-Rev. Med. Chem. 18, 26\u201341 (2017).","journal-title":"Mini-Rev. Med. Chem."},{"key":"69276_CR7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4103\/2229-5070.129142","volume":"4","author":"S Mohapatra","year":"2014","unstructured":"Mohapatra, S. Drug resistance in leishmaniasis: newer developments. Trop. Parasitol. 4, 4\u20139 (2014).","journal-title":"Trop. Parasitol."},{"key":"69276_CR8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.bbrc.2011.11.023","volume":"416","author":"A Chattopadhyay","year":"2011","unstructured":"Chattopadhyay, A. & Jafurulla, M. A novel mechanism for an old drug: Amphotericin B in the treatment of visceral leishmaniasis. Biochem. Biophys. Res. Commun. 416, 7\u201312 (2011).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"69276_CR9","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1086\/591972","volume":"47","author":"S Sundar","year":"2008","unstructured":"Sundar, S. et al. New treatment approach in Indian visceral leishmaniasis: single dose liposomal Amphotericin B followed by short course oral miltefosine. Clin. Infect. Dis. 47, 1000\u20131006 (2008).","journal-title":"Clin. Infect. Dis."},{"key":"69276_CR10","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s40265-013-0069-4","volume":"73","author":"RJ Hamill","year":"2013","unstructured":"Hamill, R. J. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs 73, 919\u2013934 (2013).","journal-title":"Drugs"},{"key":"69276_CR11","first-page":"733","volume":"3","author":"S Sundar","year":"2007","unstructured":"Sundar, S. & Olliaro, P. L. Miltefosine in the treatment of leishmaniasis: clinical evidence for informed clinical risk management. Ther. Clin. Risk Manag. 3, 733\u2013740 (2007).","journal-title":"Ther. Clin. Risk Manag."},{"key":"69276_CR12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4103\/0974-777X.62883","volume":"2","author":"EM Moore","year":"2010","unstructured":"Moore, E. M. & Lockwood, D. N. Treatment of visceral leishmaniasis. J. Glob. Infect. Dis. 2, 151\u2013158 (2010).","journal-title":"J. Glob. Infect. Dis."},{"key":"69276_CR13","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.3389\/fimmu.2017.01492","volume":"8","author":"R Kumar","year":"2017","unstructured":"Kumar, R., Chauhan, S. B., Ng, S. S., Sundar, S. & Engwerda, C. R. Immune checkpoint targets for host-directed therapy to prevent and treat leishmaniasis. Front. Immunol. 8, 1492 (2017).","journal-title":"Front. Immunol."},{"key":"69276_CR14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/646932","volume":"2014","author":"S Sundar","year":"2014","unstructured":"Sundar, S., Singh, A. & Singh, O. P. Strategies to overcome antileishmanial drugs unresponsiveness. J. Trop. Med. 2014, 1\u20137 (2014).","journal-title":"J. Trop. Med."},{"key":"69276_CR15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2147\/HIV.S143929","volume":"10","author":"JAL Lindoso","year":"2018","unstructured":"Lindoso, J. A. L., Moreira, C. H. V., Cunha, M. A. & Queiroz, I. T. Visceral leishmaniasis and HIV coinfection: current perspectives. HIV\/AIDS Res. Palliat. Care 10, 193\u2013201 (2018).","journal-title":"HIV\/AIDS Res. Palliat. Care"},{"key":"69276_CR16","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/jac\/dkt318","volume":"69","author":"E de Morais-Teixeira","year":"2014","unstructured":"de Morais-Teixeira, E., Gallupo, M. K., Rodrigues, L. F., Romanha, \u00c1J. & Rabello, A. In vitro interaction between paromomycin sulphate and four drugs with leishmanicidal activity against three New World Leishmania species. J. Antimicrob. Chemother. 69, 150\u2013154 (2014).","journal-title":"J. Antimicrob. Chemother."},{"key":"69276_CR17","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1128\/AAC.45.8.2185-2197.2001","volume":"45","author":"HW Murray","year":"2001","unstructured":"Murray, H. W. Clinical and experimental advances in treatment of visceral leishmaniasis. Antimicrob. Agents Chemother. 45, 2185\u20132197 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"69276_CR18","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijbiomac.2017.12.143","volume":"111","author":"P Chaubey","year":"2018","unstructured":"Chaubey, P., Mishra, B. & Mudavath, S. L. Mannose-conjugated curcumin-chitosan nanoparticles: efficacy and toxicity assessments against Leishmania donovani. Int. J. Biol. Macromol. 111, 109\u2013120 (2018).","journal-title":"Int. J. Biol. Macromol."},{"key":"69276_CR19","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.2217\/nnm-2018-0448","volume":"14","author":"OP Singh","year":"2019","unstructured":"Singh, O. P., Gedda, M. R., Mudavath, S. L. & Nath, O. Envisioning the innovations in nanomedicine to combat visceral leishmaniasis: for future theranostic application. Nanomedicine 14, 1911\u20131927 (2019).","journal-title":"Nanomedicine"},{"key":"69276_CR20","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2217\/nnm-2017-0255","volume":"13","author":"HS Sarwar","year":"2018","unstructured":"Sarwar, H. S., Ashraf, S., Akhtar, S., Sohail, M. F. & Syed, Z. Mannosylated thiolated polyethylenimine nanoparticles for the enhanced efficacy of antimonial drug against Leishmaniasis. Nanomedicine 13, 25\u201341 (2018).","journal-title":"Nanomedicine"},{"key":"69276_CR21","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/jac\/dkr002","volume":"66","author":"ON Srivastava","year":"2011","unstructured":"Srivastava, O. N. & Sundar, S. Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes. J. Antimicrob. Chemother. 66, 874\u2013879 (2011).","journal-title":"J. Antimicrob. Chemother."},{"key":"69276_CR22","first-page":"1235","volume":"8","author":"SL Mudavath","year":"2014","unstructured":"Mudavath, S. L., Talat, M., Rai, M., Srivastava, O. N. & Sundar, S. Characterization and evaluation of amine-modified graphene amphotericin B for the treatment of visceral leishmaniasis: in vivo and in vitro studies. Drug Des. Dev. Ther. 8, 1235\u20131247 (2014).","journal-title":"Drug Des. Devel. Ther."},{"key":"69276_CR23","first-page":"32","volume":"18","author":"B Monge-Maiho","year":"2016","unstructured":"Monge-Maiho, B. & Lopez-Velez, R. Treatment options for visceral leishmaniasis and HIV coinfection. AIDS Rev. 18, 32\u201343 (2016).","journal-title":"AIDS Rev."},{"key":"69276_CR24","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.msec.2016.05.119","volume":"68","author":"M Geszke-Moritz","year":"2016","unstructured":"Geszke-Moritz, M. & Moritz, M. Solid lipid nanoparticles as attractive drug vehicles: composition, properties and therapeutic strategies. Mater. Sci. Eng. C 68, 982\u2013994 (2016).","journal-title":"Mater. Sci. Eng. C"},{"key":"69276_CR25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.15171\/apb.2016.06","volume":"6","author":"ZM Adib","year":"2016","unstructured":"Adib, Z. M., Ghanbarzadeh, S., Kouhsoltani, M., Khosroshahi, A. Y. & Hamishehkar, H. The effect of particle size on the deposition of solid lipid nanoparticles in different skin layers: a histological study. Adv. Pharm. Bull. 6, 31\u201336 (2016).","journal-title":"Adv. Pharm. Bull."},{"key":"69276_CR26","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1208\/s12249-015-0439-1","volume":"17","author":"MH Kharaji","year":"2015","unstructured":"Kharaji, M. H., Doroud, D., Taheri, T. & Rafati, S. Drug targeting to macrophages with solid lipid nanoparticles harboring paromomycin: an in vitro evaluation against L. major and L. tropica. AAPS PharmSciTech. 17, 1110\u20131119 (2015).","journal-title":"AAPS PharmSciTech"},{"key":"69276_CR27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/750891","volume":"2012","author":"P Severino","year":"2012","unstructured":"Severino, P. et al. Current state-of-art and new trends on lipid nanoparticles (SLN and NLC) for oral drug delivery. J. Drug Deliv. 2012, 1\u201310 (2012).","journal-title":"J. Drug Deliv."},{"key":"69276_CR28","doi-asserted-by":"crossref","first-page":"691","DOI":"10.4155\/tde-2016-0038","volume":"7","author":"H Ali","year":"2016","unstructured":"Ali, H. & Singh, S. K. Biological voyage of solid lipid nanoparticles: a proficient carrier in nanomedicine. Ther. Deliv. 7, 691\u2013709 (2016).","journal-title":"Ther. Deliv."},{"key":"69276_CR29","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1021\/cr970022c","volume":"98","author":"J Szejtli","year":"1998","unstructured":"Szejtli, J. Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743\u20131754 (1998).","journal-title":"Chem. Rev."},{"key":"69276_CR30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0378-5173(01)00761-X","volume":"225","author":"T Loftsson","year":"2001","unstructured":"Loftsson, T. & Masson, M. Cyclodextrins in topical drug formulations: theory and practice. Int. J. Pharm. 225, 15\u201330 (2001).","journal-title":"Int. J. Pharm."},{"key":"69276_CR31","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0169-409X(98)00056-8","volume":"36","author":"H Matsuda","year":"1999","unstructured":"Matsuda, H. & Arima, H. Cyclodextrins in transdermal and rectal delivery. Adv. Drug Deliv. Rev. 36, 81\u201399 (1999).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"69276_CR32","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1021\/js960075u","volume":"85","author":"RA Rajewski","year":"1996","unstructured":"Rajewski, R. A. & Stella, V. J. Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery. J. Pharm. Sci. 85, 1142\u20131169 (1996).","journal-title":"J. Pharm. Sci."},{"key":"69276_CR33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0169-409X(98)00058-1","volume":"36","author":"F Hirayama","year":"1999","unstructured":"Hirayama, F. & Uekama, K. Cyclodextrin-based controlled drug release system. Adv. Drug Deliv. Rev. 36, 125\u2013141 (1999).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"69276_CR34","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1007\/s11051-010-9998-y","volume":"13","author":"D Liu","year":"2011","unstructured":"Liu, D. et al. Diclofenac sodium-loaded solid lipid nanoparticles prepared by emulsion\/solvent evaporation method. J. Nanopart. Res. 13, 2375\u20132386 (2011).","journal-title":"J. Nanoparticle Res."},{"key":"69276_CR35","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0378-5173(03)00135-2","volume":"257","author":"M Trotta","year":"2003","unstructured":"Trotta, M., Debernardi, F. & Caputo, O. Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique. Int. J. Pharm. 257, 153\u2013160 (2003).","journal-title":"Int. J. Pharm."},{"key":"69276_CR36","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.2042-7158.2012.01578.x","volume":"65","author":"J Baek","year":"2013","unstructured":"Baek, J. & Cho, C. 2-Hydroxypropyl-\u03b2-cyclodextrin-modified SLN of paclitaxel for overcoming p-glycoprotein function in multidrug-resistant breast cancer cells. J. Pharm. Pharmacol. 65, 72\u201378 (2013).","journal-title":"J. Pharm. Pharmacol."},{"key":"69276_CR37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ijpharm.2007.12.007","volume":"355","author":"AA Attama","year":"2008","unstructured":"Attama, A. A., Reichl, S. & Christel, C. M. Diclofenac sodium delivery to the eye: in vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct. Int. J. Pharm. 355, 307\u2013313 (2008).","journal-title":"Int. J. Pharm."},{"key":"69276_CR38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/1920-4159.1000212","volume":"8","author":"P Kumar","year":"2016","unstructured":"Kumar, P. & Bose, P. P. Targeted delivery of paromomycin to leishmania infected macrophage by hemoglobin tagged nanocarrier. J. Appl. Pharm. 8, 1\u20136 (2016).","journal-title":"J. Appl. Pharm."},{"key":"69276_CR39","doi-asserted-by":"crossref","first-page":"71705","DOI":"10.1039\/C6RA06007B","volume":"6","author":"PK Singh","year":"2016","unstructured":"Singh, P. K. et al. Macrophage-targeted chitosan anchored PLGA nanoparticles bearing doxorubicin and amphotericin B against visceral leishmaniasis. RSC Adv. 6, 71705\u201371718 (2016).","journal-title":"RSC Adv."},{"key":"69276_CR40","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ejps.2017.03.046","volume":"104","author":"N Kar","year":"2017","unstructured":"Kar, N., Chakraborty, S., De, A. K., Ghosh, S. & Bera, T. Development and evaluation of a cedrol-loaded nanostructured lipid carrier system for in vitro and in vivo susceptibilities of wild and drug resistant Leishmania donovani amastigotes. Eur. J. Pharm. Sci. 104, 196\u2013211 (2017).","journal-title":"Eur. J. Pharm. Sci."},{"key":"69276_CR41","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1208\/s12248-010-9203-3","volume":"12","author":"S Klein","year":"2010","unstructured":"Klein, S. The use of biorelevant dissolution media to forecast the in vivo performance of a drug. AAPS PharmSciTech. 12, 397\u2013406 (2010).","journal-title":"AAPS PharmSciTech"},{"key":"69276_CR42","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.ijbiomac.2017.07.161","volume":"105","author":"PK Singh","year":"2017","unstructured":"Singh, P. K. et al. Chitosan coated PluronicF127 micelles for effective delivery of Amphotericin B in experimental visceral leishmaniasis. Int. J. Biol. Macromol. 105, 1220\u20131231 (2017).","journal-title":"Int. J. Biol. Macromol."},{"key":"69276_CR43","doi-asserted-by":"crossref","first-page":"911","DOI":"10.2147\/DDDT.S97738","volume":"10","author":"C Wu","year":"2016","unstructured":"Wu, C. et al. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics. Drug Des. Dev. Ther. 10, 911\u2013925 (2016).","journal-title":"Drug Des. Dev. Ther."},{"key":"69276_CR44","first-page":"1241","volume":"23","author":"M Nahar","year":"2009","unstructured":"Nahar, M., Mishra, D., Dubey, V. & Jain, N. K. Development of amphotericin B loaded PLGA nanoparticles for effective treatment of visceral leishmaniasis. Colloids Surf. B Biointerfaces 23, 1241\u20131243 (2009).","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"69276_CR45","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1128\/AAC.47.12.3774-3779.2003","volume":"47","author":"M Larabi","year":"2003","unstructured":"Larabi, M. et al. Toxicity and antileishmanial activity of a new stable lipid suspension of amphotericin B. Antimicrob. Agents Chemother. 47, 3774\u20133779 (2003).","journal-title":"Antimicrob. Agents Chemother."},{"key":"69276_CR46","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0168-3659(90)90103-Z","volume":"12","author":"HC Roland Bodmeier","year":"1990","unstructured":"Roland Bodmeier, H. C. Indomethacin polymeric nanosuspensions prepared by microfujidization. J. Control. Release 12, 223\u2013233 (1990).","journal-title":"J. Control. Release"},{"key":"69276_CR47","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1080\/10611860701195395","volume":"15","author":"S Gupta","year":"2007","unstructured":"Gupta, S. & Vyas, S. P. Development and characterization of amphotericin B bearing emulsomes for passive and active macrophage targeting. J. Drug Target 15, 206\u2013217 (2007).","journal-title":"J. Drug Target."},{"key":"69276_CR48","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1208\/s12249-014-0279-4","volume":"16","author":"H Amekyeh","year":"2015","unstructured":"Amekyeh, H., Billa, N., Yuen, K., Lim, S. & Chin, S. A gastrointestinal transit study on Amphotericin B-loaded solid lipid nanoparticles in rats. AAPS PharmSciTech. 16, 871\u2013877 (2015).","journal-title":"AAPS PharmSciTech"},{"key":"69276_CR49","first-page":"1498","volume":"15","author":"MN Patel","year":"2014","unstructured":"Patel, M. N. et al. Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique. AA 15, 1498\u20131508 (2014).","journal-title":"AA"},{"key":"69276_CR50","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.colsurfb.2015.07.032","volume":"139","author":"D Butani","year":"2016","unstructured":"Butani, D., Yewale, C. & Misra, A. Topical amphotericin B solid lipid nanoparticles: design and development. Colloids Surf. B Biointerfaces 139, 17\u201324 (2016).","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"69276_CR51","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3109\/1061186X.2010.492524","volume":"19","author":"W Khan","year":"2011","unstructured":"Khan, W. & Kumar, N. Drug targeting to macrophages using paromomycin-loaded albumin microspheres for treatment of visceral leishmaniasis: an in vitro evaluation. J. Drug Target. 19, 239\u2013250 (2011).","journal-title":"J. Drug Target."},{"key":"69276_CR52","first-page":"1","volume":"7","author":"SR Kumar","year":"2016","unstructured":"Kumar, S. R., Marianna, L. & Gianni, S. Synthesis and characterization of chitosan-coated magnetite nanoparticles and their application in curcumin drug delivery. Adv. Nat. Sci. Nanosci. Nanotechnol. 7, 1\u20139 (2016).","journal-title":"Adv. Nat. Sci. Nanosci. Nanotechnol."},{"key":"69276_CR53","first-page":"13","volume":"12","author":"S Das","year":"2011","unstructured":"Das, S. & Chaudhury, A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech. 12, 13\u201315 (2011).","journal-title":"AAPS PharmSciTech"},{"key":"69276_CR54","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s11483-019-09588-w","volume":"14","author":"V Wiedenmann","year":"2019","unstructured":"Wiedenmann, V. Heat stability of differently stabilized solid lipid nanoparticles in the presence of excess bulk phase protein. Food Biophys.\u00a014, 393\u2013402 (2019).","journal-title":"Food Biophys."},{"key":"69276_CR55","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ijpharm.2017.01.004","volume":"518","author":"PL Goto","year":"2017","unstructured":"Goto, P. L., Siqueira-moura, M. P. & Tedesco, A. C. Application of aluminum chloride phthalocyanine-loaded solid lipid nanoparticles for photodynamic inactivation of melanoma cells. Int. J. Pharm. 518, 228\u2013241 (2017).","journal-title":"Int. J. Pharm."},{"key":"69276_CR56","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0939-6411(98)00074-5","volume":"47","author":"C Freitas","year":"1999","unstructured":"Freitas, C. & Muller, R. H. Correlation between long-term stability of solid lipid nanoparticles (SLN\u2122) and crystallinity of the lipid phase. Eur. J. Pharm. Biopharm. 47, 125\u2013132 (1999).","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"69276_CR57","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.3390\/ijms9122376","volume":"9","author":"L Zhang","year":"2008","unstructured":"Zhang, L. et al. Improving the stability of insulin in solutions containing intestinal proteases in vitro. Int. J. Mol. Sci. 9, 2376\u20132387 (2008).","journal-title":"Int. J. Mol. Sci."},{"key":"69276_CR58","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.fct.2005.03.007","volume":"43","author":"S Gould","year":"2005","unstructured":"Gould, S. & Scott, R. C. 2-hydroxypropyl-b-cyclodextrin (HP-b-CD): a toxicology review. Food Chem. Toxicol. 43, 1451\u20131459 (2005).","journal-title":"Food Chem. Toxicol."},{"key":"69276_CR59","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.3390\/ijms10052031","volume":"10","author":"L Zhang","year":"2009","unstructured":"Zhang, L. et al. Effects of hydroxylpropyl-\u03b2-cyclodextrin on in vitro insulin stability. Int. J. Mol. Sci. 10, 2031\u20132040. https:\/\/doi.org\/10.3390\/ijms10052031 (2009).","journal-title":"Int. J. Mol. Sci."},{"key":"69276_CR60","first-page":"151","volume":"6","author":"S Nie","year":"2011","unstructured":"Nie, S. Thermoreversible Pluronic \u00ae F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies. Int. J. Nanomed. 6, 151\u2013166 (2011).","journal-title":"Int. J. Nanomed."},{"key":"69276_CR61","first-page":"467","volume":"7544","author":"A Seyfoddin","year":"2017","unstructured":"Seyfoddin, A. et al. Solid lipid nanoparticles for ocular drug delivery solid lipid nanoparticles for ocular drug delivery. Drug Deliv. 7544, 467\u2013489 (2017).","journal-title":"Drug Deliv."},{"key":"69276_CR62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/8690145","volume":"2019","author":"R Cassano","year":"2019","unstructured":"Cassano, R. & Trombino, S. Solid lipid nanoparticles based on L-cysteine for progesterone intravaginal delivery. Int. J. Polym. Sci. 2019, 1\u201310 (2019).","journal-title":"Int. J. Polym. Sci."},{"key":"69276_CR63","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.apsb.2014.10.005","volume":"4","author":"M Yasir","year":"2014","unstructured":"Yasir, M., Vir, U. & Sara, S. Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation. Acta Pharm. Sin. B 4, 454\u2013463 (2014).","journal-title":"Acta Pharm. Sin. B"},{"key":"69276_CR64","first-page":"1256","volume":"3","author":"R Nair","year":"2011","unstructured":"Nair, R., Vishnu, K., Kumar, K. S. A., Badivaddin, T. & Sevukarajan, M. Formulation and evaluation of solid lipid nanoparticles of water soluble drug: isoniazid. J. Pharm. Sci. Res. 3, 1256\u20131264 (2011).","journal-title":"J. Pharm. Sci. Res."},{"key":"69276_CR65","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1517\/17425247.2014.889678","volume":"11","author":"R Khatik","year":"2014","unstructured":"Khatik, R., Dwivedi, P., Khare, P. & Kansal, S. Development of targeted L -serine-coated gelatin nanoparticles loaded with amphotericin B for improved in vitro and in vivo effect in leishmaniasis. Expert Opin. Drug Deliv. 11, 633\u2013646 (2014).","journal-title":"Expert Opin. Drug Deliv."},{"key":"69276_CR66","first-page":"5397","volume":"10","author":"J Baek","year":"2015","unstructured":"Baek, J., Kim, J., Park, J. & Cho, C. Modification of paclitaxel-loaded solid lipid nanoparticles with 2-hydroxypropyl-\u03b2-cyclodextrin enhances absorption and reduces nephrotoxicity associated with intravenous injection. Int. J. Nanomed. 10, 5397\u20135405 (2015).","journal-title":"Int. J. Nanomed."},{"key":"69276_CR67","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/j.carbpol.2011.10.002","volume":"87","author":"L Zhang","year":"2012","unstructured":"Zhang, L., Song, L., Zhang, C. & Ren, Y. Improving intestinal insulin absorption efficiency through coadministration of cell-penetrating peptide and hydroxypropyl-\u03b2-cyclodextrin. Carbohydr. Polym. 87, 1822\u20131827 (2012).","journal-title":"Carbohydr. Polym."},{"key":"69276_CR68","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.actatropica.2016.02.017","volume":"158","author":"P Bhattacharya","year":"2016","unstructured":"Bhattacharya, P. et al. In vitro susceptibilities of wild and drug resistant Leishmania donovani amastigotes to piperolactam A loaded hydroxypropyl-\u03b2-cyclodextrin nanoparticles. Acta Trop. 158, 97\u2013106 (2016).","journal-title":"Acta Trop."},{"key":"69276_CR69","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1128\/AAC.48.1.100-103.2004","volume":"48","author":"C Demicheli","year":"2004","unstructured":"Demicheli, C. et al. Oral delivery of meglumine antimoniate-\u03b2-cyclodextrin complex for treatment of leishmaniasis. Antimicrob. Agents Chemother. 48, 100\u2013103 (2004).","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69276-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69276-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69276-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T10:03:36Z","timestamp":1670321016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69276-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,22]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["69276"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-69276-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,22]]},"assertion":[{"value":"31 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12243"}}