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dc.creatorIlić, Tanja
dc.creatorSavić, Sanela
dc.creatorBatinić, Bojan
dc.creatorMarković, Bojan
dc.creatorSchmidberger, Markus
dc.creatorLunter, Dominique
dc.creatorSavić, Miroslav
dc.creatorSavić, Snežana
dc.date.accessioned2019-09-02T12:03:27Z
dc.date.available2019-09-02T12:03:27Z
dc.date.issued2018
dc.identifier.issn0928-0987
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3047
dc.description.abstractThis study aimed to investigate the potential of lecithin-based nanoemulsions costabilized by sucrose esters, with and without skin pretreatment with stainless steel microneedles, to improve delivery of aceclofenac, as a model drug, into/across the skin. The characterization revealed favorable droplet size (about 180 nm), narrow size distribution ( lt 0.15), high surface charge (about - 40 mV) and satisfying long-term stability (one year at 4 +/- 1 degrees C) of the formulation costabilized by sucrose palmitate, demonstrating a similar trend observed for the reference stabilized by widely used lecithin/polysorbate 80 combination. In vitro release/permeation testing and differential stripping on the porcine ear proved the superiority of the sucrose ester- over polysorbate-based nanoemulsion. However, in vitro findings were not fully indicative of the in vivo performances - no significant differences were observed between investigated formulations in pharmacokinetic profile and total amount of aceclofenac deposited in the rat skin 24 h after dosing, simultaneously pointing to delayed aceclofenac delivery into the systemic circulation. In addition, the ratio of plasma concentrations of aceclofenac and its major metabolite in rats, diclofenac, was remarkably changed after topical application of tested nanoemulsions compared to intravenous administration of aceclofenac solution. Finally, skin pretreatment with microneedles improved aceclofenac delivery into/across the rat skin from tested formulations, resulting in 1.4-2.1-fold increased bioavailability and 1.2-1.7-fold enhanced level of aceclofenac retained in the skin, as measured 24 h after administration. Moreover, the plasma concentrations of aceclofenac 24 h after application of tested formulations (lecithin/sucrose palmitate vs. lecithin/polysorbate 80) combined with microneedles (173.37 +/- 40.50 ng/ml vs. 259.23 +/- 73.18 ng/ml) were significantly higher than those obtained through intact skin (105.69 +/- 19.53 ng/ml vs. 88.38 +/- 14.46 ng/ml). However, obtained results suggest that combination of microneedles and sucrose palmitate-costabilized nanoemulsion could be useful to attain higher skin concentration, while combination of microneedles with polysorbate 80-costabilized nanoemulsion could be a preferable option for enhancing drug delivery into the bloodstream.en
dc.publisherElsevier Science BV, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Technological Development (TD or TR)/34031/RS//
dc.rightsrestrictedAccess
dc.sourceEuropean Journal of Pharmaceutical Sciences
dc.subjectAceclofenacen
dc.subjectStainless steel microneedlesen
dc.subjectIn vitro drug releaseen
dc.subjectIn vitro skin permeationen
dc.subjectDifferential strippingen
dc.subjectIn vivo pharmacokineticsen
dc.titleCombined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studiesen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractСцхмидбергер, Маркус; Савић, Мирослав; Лунтер, Доминиqуе; Савић, Снежана; Марковић, Бојан; Илић, Тања; Савић, Санела; Батинић, Бојан;
dc.citation.volume125
dc.citation.spage110
dc.citation.epage119
dc.citation.other125: 110-119
dc.citation.rankM21
dc.identifier.wos000448169800012
dc.identifier.doi10.1016/j.ejps.2018.09.023
dc.identifier.pmid30287408
dc.identifier.scopus2-s2.0-85054180168
dc.identifier.rcubconv_4239
dc.type.versionpublishedVersion


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