Improved Topical Delivery of Sorafenib-Meglumine Antimoniate: Elastic Nano-Liposomal Formulation for the Treatment of Cutaneous Leishmaniasis
Sorafenib-Meglumine Antimoniate Nano-Liposomal Formulation for CL
ABSTRACT
Background: Cutaneous leishmaniasis (CL) is a widespread parasitic disease with significant health and social impacts. Current systemic treatments have severe side effects, highlighting the need for effective topical alternatives.
Objective: This study aimed to develop and evaluate the effectiveness of sorafenib (SF) and meglumine antimoniate (MM) dual-loaded transferosomes (TRs) for topical treatment of CL.
Methods: TRs were prepared using a thin film hydration method and incorporated into a carbopol gel. The formulations were characterized for vesicle size, zeta potential, entrapment efficiency, and deformability index. In vivo and ex vivo skin permeation studies were conducted, along with anti-leishmanial efficacy testing on an intramacrophage amastigote model using BALB/c mice.
Results: The TRs exhibited a vesicle size of 186.1 ± 65.89 nm, zeta potential of -27.9 mV, and entrapment efficiency of 71.7 ± 3.9% for MM and 78.6 ± 4.2% for SF. Ex vivo studies showed enhanced skin permeation with cumulative permeation of 327.6 ± 29.4 μg/cm² for MM and 291.6 ± 28.3 μg/cm² for SF. In vivo results indicated a significant reduction in lesion size (0.1 ± 0.12 mm) and parasite load (2.7 ± 0.3 log scale).
Conclusion: The MM-SF dual-loaded TRs demonstrated effective topical delivery and therapeutic potential for CL, providing a promising alternative to systemic treatments.
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Materials and Methods
The study adhered to ethical standards for animal research as outlined by the National Research Council’s “Guide for the Care and Use of Laboratory Animals.” Female BALB/c mice were obtained from the National Institute of Health (NIH), Islamabad, and housed under standard laboratory conditions, including a controlled temperature of 25 ± 1°C, 55 ± 5% humidity, and a 12-hour light/dark cycle. Mice were provided with a standard laboratory diet and fresh water ad libitum. All animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Lahore, Islamabad Campus, ensuring compliance with ethical guidelines for the humane treatment of laboratory animals. Parasites used in the study were transgenic Leishmania mexicana expressing red fluorescent protein, isolated from the draining lymph nodes of previously infected BALB/c mice. These parasites were cultured in complete M-199 medium supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin, and 1% HEPES, and maintained at 25°C in culture flasks. Promastigotes were allowed to grow to the log phase before further experimentation. The MM-SF dual-loaded nano elastic liposomes (NELs), also referred to as transferosomes (TRs), were prepared using the thin film hydration technique with modifications as previously described (21). Phospholipids (Phospholipon 90G), sodium cholate, and SF were dissolved in a methanol mixture (1:1) to create a thin film on a rotary evaporator under vacuum at 40°C. The resultant film was hydrated with an MM solution in phosphate buffer saline (PBS) at pH 7.4 for one hour at 60°C. The prepared liposomal suspension was then extruded manually through 450 nm and 200 nm polycarbonate membrane filters to achieve the desired size and homogeneity. The unentrapped drug was removed by dialysis against PBS at 4°C, and the final formulation was stored in airtight glass containers at 4°C for subsequent characterization and testing.
Nasir Khan, Muhammad Junaid Dar, Soumayya Aib, Sidra Khalid, Kashif Iqbal, & Ghulam Razaque. (2024). Improved Topical Delivery of Sorafenib-Meglumine Antimoniate: Elastic Nano-Liposomal Formulation for the Treatment of Cutaneous Leishmaniasis: Sorafenib-Meglumine Antimoniate Nano-Liposomal Formulation for CL. Journal of Health and Rehabilitation Research, 4(3). https://doi.org/10.61919/jhrr.v4i3.1287.
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