Mannosylated imiquimod-terbinafine co-loaded transethosomes for cutaneous leishmaniasis; assessment of its anti-leishmanial potential, in vivo safety and immune response modulation
- Authors
- Jamshaid,Humzah; Din, Fakhar ud; Nousheen, Kainat; Khan, Saif Ullah; Fatima,Anam; Khan, Salman; Choi, Han Gon; Khan, Gul Majid
- Issue Date
- Feb-2023
- Publisher
- Elsevier Ltd
- Keywords
- Anti-leishmanial; Imiquimod; Mannosylated transethosomal gel; Nano transethosomes; Terbinafine
- Citation
- Biomaterials Advances, v.145, pp 1 - 19
- Pages
- 19
- Indexed
- SCIE
SCOPUS
- Journal Title
- Biomaterials Advances
- Volume
- 145
- Start Page
- 1
- End Page
- 19
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/112957
- DOI
- 10.1016/j.bioadv.2022.213266
- ISSN
- 2772-9508
2772-9508
- Abstract
- Current treatment options for cutaneous leishmaniasis are associated with myriad limiting factors including low penetration, poor efficacy, and drug toxicities. Herein, we reported imiquimod and terbinafine co-loaded mannosylated transethosomes (IMQ-TER-MTES) with enhanced cutaneous retention, macrophage targeting, anti-leishmanial potential, and dermal immunomodulation. IMQ-TER-MTES were optimized using Design Expert® followed by their loading into chitosan gel. Moreover, the antileishmanial response against amastigotes-infected macrophages and Leishmania-infected BALB/c mice was evaluated. Finally, the safety and immunomodulation activity of IMQ-TER-MTES gel was performed using BALB/c mice. Optimized IMQ-TER-MTES showed nano-sized particles with low poly-dispersibility index (PDI) and high drug entrapment. Mannosylation has augmented macrophage targeting and the internalization capability of TES. IMQ-TER-MTES showed significantly reduced IC50 value (19.56 ± 3.62 μg/ml), higher selectivity index (29.24), and synergism against Leishmania major (L. major) amastigotes. In L. major infected BALB/c mice, the cutaneous lesion healing potential of IMQ-TER-MTES was also elevated with reduced lesion size (1.52 ± 0.43 mm). Superior safety of IMQ-TER-MTES was observed in BALB/c mice along with adequate stimulation of dermal immune cells, in contrast to the ALDARA®. Moreover, incremented Nuclear factor Kappa-β (NF-κβ) and nitric oxide (NO) biosynthesis were observed with IMQ-TER-MTES. © 2022 Elsevier B.V.
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