TY  - JOUR
AU  - Ilić, Tanja
AU  - Savić, Sanela
AU  - Batinić, Bojan
AU  - Marković, Bojan
AU  - Schmidberger, Markus
AU  - Lunter, Dominique
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3047
AB  - This 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.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies
VL  - 125
SP  - 110
EP  - 119
DO  - 10.1016/j.ejps.2018.09.023
ER  - 

@article{
author = "Ilić, Tanja and Savić, Sanela and Batinić, Bojan and Marković, Bojan and Schmidberger, Markus and Lunter, Dominique and Savić, Miroslav and Savić, Snežana",
year = "2018",
abstract = "This 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.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies",
volume = "125",
pages = "110-119",
doi = "10.1016/j.ejps.2018.09.023"
}

Ilić, T., Savić, S., Batinić, B., Marković, B., Schmidberger, M., Lunter, D., Savić, M.,& Savić, S.. (2018). Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 125, 110-119.
https://doi.org/10.1016/j.ejps.2018.09.023

Ilić T, Savić S, Batinić B, Marković B, Schmidberger M, Lunter D, Savić M, Savić S. Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies. in European Journal of Pharmaceutical Sciences. 2018;125:110-119.
doi:10.1016/j.ejps.2018.09.023 .

Ilić, Tanja, Savić, Sanela, Batinić, Bojan, Marković, Bojan, Schmidberger, Markus, Lunter, Dominique, Savić, Miroslav, Savić, Snežana, "Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies" in European Journal of Pharmaceutical Sciences, 125 (2018):110-119,
https://doi.org/10.1016/j.ejps.2018.09.023 . .