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Preparation, optimization, and in vitro–in vivo evaluation of sorafenib-loaded polycaprolactone and cellulose acetate nanofibers for the treatment of cutaneous leishmaniasis

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Abstract

The most common form of leishmaniasis is cutaneous leishmaniasis (CL). The major difficulties in the treatment of leishmaniasis include emergence of resistance, toxicity, long-term treatment, and the high cost of the current drugs. Although the therapeutic effect of sorafenib (SF) has been demonstrated in both in vitro and in vivo models of Leishmania infection, the therapeutic applications are limited due to severe drug-related toxicity; this is, in turn, due to non-specific distribution in the body. Thus, topical delivery has the advantage of the site directed delivery of SF. This research study evaluated SF-loaded hybrid nanofibers (NFs) which were composed of polycaprolactone (PCL) and cellulose acetate (CA) for the CL topical treatment. Accordingly, SF-loaded hybrid NFs were prepared using the electrospinning method. Formulation variables including total polymer concentration, drug/polymer ratio, and CA concentration were optimized using a full factorial design. The prepared SF-loaded NFs were then characterized for morphology, diameter, encapsulation efficiency (EE)%, drug loading (DL) %, and percentage of release efficiency during a 24-h period (RE24h%); the mechanical characteristics were also considered. The physical state of the drug in the optimized NF was evaluated by the X-ray diffraction analysis. Finally, its in vivo efficacy was determined in L. major–infected mice. The optimized formulation had a smooth, cylindrical, non-beaded shape fiber with a diameter of 281.44 nm, EE of 97.96%, DL of 7.48%, RE of 51.05%, ultimate tensile strength of 1.08 MPa, and Young’s moduli of 74.96 MPa. The XRD analysis also demonstrated the amorphous state of SF in NF. Further, the in vivo results displayed the higher anti-leishmanial activity of the SF-loaded hybrid NF by efficiently healing lesion and successfully reducing the parasite burden. This, thus, indicated the potential of the clinical capability of the SF-loaded hybrid NF for the effective treatment of CL.

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Funding

The current research was supported by Research Vice Chancellery of Isfahan University of Medical Sciences (grant number 399358).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, PO Box 81745-359, Isfahan, Iran

    Mahsa Alemomen, Somayeh Taymouri & Jaleh Varshosaz

  2. Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Sedigheh Saberi

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  1. Mahsa Alemomen
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Correspondence to Somayeh Taymouri.

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All experiments were performed as per the guidelines directed by the Ethical Committee of Isfahan University of Medical Sciences in regard to the care and use of laboratory animals (ethics code number # IR.MUI.RESEARCH.REC.1399.489).

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Alemomen, M., Taymouri, S., Saberi, S. et al. Preparation, optimization, and in vitro–in vivo evaluation of sorafenib-loaded polycaprolactone and cellulose acetate nanofibers for the treatment of cutaneous leishmaniasis. Drug Deliv. and Transl. Res. 13, 862–882 (2023). https://doi.org/10.1007/s13346-022-01250-2

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