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Antileishmanial Agents Co-loaded in Transfersomes with Enhanced Macrophage Uptake and Reduced Toxicity

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Abstract

The prime objective of this study was to develop amphotericin B (AMB) and rifampicin (RIF) co-loaded transfersomal gel (AMB-RIF co-loaded TFG) for effective treatment of cutaneous leishmaniasis (CL). AMB-RIF co-loaded TF was prepared by the thin-film hydration method and was optimized based on particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (%EE), and deformability index. Similarly, AMB-RIF co-loaded TFG was characterized in terms of rheology, spread ability, and pH. In vitro, ex vivo, and in vivo assays were performed to evaluate AMB-RIF co-loaded TF as a potential treatment option for CL. The optimized formulation had vesicles in nanosize range (167 nm) with suitable PDI (0.106), zeta potential (− 19.05 mV), and excellent %EE of RIF (66%) and AMB (85%). Moreover, it had appropriate deformability index (0.952). Additionally, AMB-RIF co-loaded TFG demonstrated suitable rheological behavior for topical application. AMB-RIF co-loaded TF and AMB-RIF co-loaded TFG showed sustained release of the incorporated drugs as compared to AMB-RIF suspension. Furthermore, RIF permeation from AMB-RIF co-loaded TF and AMB-RIF co-loaded TFG was enhanced fivefold and threefold, whereas AMB permeation was enhanced by eightfold and 6.6-fold, respectively. The significantly different IC50, higher CC50, and FIC50 (p < 0.5) showed synergistic antileishmanial potential of AMB-RIF co-loaded TF. Likewise, reduced lesion size and parasitic burden in AMB-RIF co-loaded TF–treated mouse group further established the antileishmanial effect of the optimized formulation. Besides, AMB-RIF co-loaded TFG showed a better safety profile. This study concluded that TFG may be a suitable carrier for co-delivery of AMB-RIF when administered topically for the treatment of CL.

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Abbreviations

AMB:

Amphotericin B

AMB-RIF co-loaded TF:

Amphotericin B and rifampicin co-loaded into transfersomes

AMB-RIF co-loaded TFG:

Amphotericin B and rifampicin co-loaded into transfersomal gel

EA:

Edge activator

FBS:

Fetal bovine serum

NaCh:

Sodium cholate

PDI:

Polydispersity index

DLS:

Dynamic light scattering

PDII:

Primary dermal irritation index

PL90G:

Phospholipon 90G

RIF:

Rifampicin

S80:

Span 80

TF:

Transfersomes

Stratum corneum:

SC

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Acknowledgements

The authors are thankful to Dr. Ihsan ul Haq, Quaid-i-Azam University, Islamabad, Pakistan, for providing technical and administrative help in conducting this research.

Funding

This research work was supported by the Higher Education Commission (HEC) of Pakistan under the National Research Support Program for Universities (NRPU) with a project No: 6171/Federal/ NRPU/R&D/HEC/2016.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan

    Fatima Zahid, Sibgha Batool, Fakhar ud-Din, Zakir Ali, Salman Khan & Gul Majid Khan

  2. Institute of Pharmaceutical Sciences, Khyber Medical University, Peshawar, Pakistan

    Muhammad Nabi

  3. Department of Pharmacy, Forman Christian University, Lahore, Pakistan

    Omer Salman

  4. Islamia College University, Peshawar, Khyber Pakhtunkhwa, Pakistan

    Gul Majid Khan

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  1. Fatima Zahid
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  2. Sibgha Batool
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Contributions

Fatima Zahid: analysis, investigation, writing first draft.

Sibgha Batool: methodology, software, investigation

Fakhar Ud Din: idea, project administration, supervision, approval of the final draft

Zakir Ali: methodology, analysis, revising the draft

Muhammad Nabi: methodology, analysis, revising the draft

Salman Khan: data curation, resources, validation

Omer Salman: data curation, validation, interpretation

Gul Majid Khan: funding, project administration, supervision

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Correspondence to Fakhar ud-Din or Gul Majid Khan.

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Zahid, F., Batool, S., ud-Din, F. et al. Antileishmanial Agents Co-loaded in Transfersomes with Enhanced Macrophage Uptake and Reduced Toxicity. AAPS PharmSciTech 23, 226 (2022). https://doi.org/10.1208/s12249-022-02384-9

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