Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 88, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2023.104887
Keywords
Topical silymarin; Spanethosomes; Spanlastics; Ethanol injection; Factorial design; Quality by design
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A novel vesicular system, spanethosomes, was developed by introducing ethanol into spanlastics, showing improved drug encapsulation efficiency, drug release, and cellular uptake compared to spanlastics.
Spanlastics which are nanovesicles composed of nonionic surfactant and edge activator have recently emerged as a promising topical/transdermal drug delivery carrier, to overcome the challenging properties of the stratum corneum. In the current work, a novel vesicular system; spanethosomes, was developed by introducing ethanol within spanlastics, to combine both the skin penetration enhancing ability of spanlastics and the fluidizing effect of ethanol. For comparative purposes, spanethosomes and spanlastics loading silymarin were prepared using the ethanol injection technique, for possible treatment of cutaneous leishmaniasis. Results revealed that spanetho-somes achieved higher entrapment efficiency (88.52 +/- 0.63%) than spanlastics (81.00 +/- 0.33%), larger hydrodynamic diameter, and higher drug release after 72 h. The IC50 values of spanethosomes (344.37 +/- 3.87 mu g/ mL) and spanlastics (303.03 +/- 8.96 mu g/mL) indicated their cytocompatibility. Spanethosomes exhibited marked cellular internalization (60.93 +/- 2.65%) in human fibroblasts, higher epidermal (55.02 +/- 0.66%) and dermal (42.02 +/- 0.26%) deposition, and superior inhibitory effect towards leishmanial trypanothione reductase up to 89.66 +/- 1.42% compared to spanlastics which exhibited cellular uptake of 39.99 +/- 2.81%, epidermal deposition of 42.40 +/- 0.57%, dermal deposition of 35.84 +/- 1.34%, and lower trypanothione reductase inhibition activity (78.30 +/- 1.26%). The aforementioned results delineate spanethosomes as a novel promising topical delivery system, with noticeable superiority over spanlastics in skin delivery of drugs having antileishmanial activity.
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