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
DOI:
https://doi.org/10.61919/jhrr.v4i3.1287Keywords:
Cutaneous Leishmaniasis, Sorafenib, Meglumine antimoniate, Transferosomes, Nano elastic liposomes, Macrophage uptakeAbstract
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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References
Saqib M, Ali Bhatti AS, Ahmad NM, Ahmed N, Shahnaz G, Lebaz N, et al. Amphotericin B Loaded Polymeric Nanoparticles for Treatment of Leishmania Infections. Nanomaterials. 2020;10(6):1152.
Tonui WK, Titus RG. Cross-Protection Against Leishmania Donovani but Not L. Braziliensis Caused by Vaccination with L. Major Soluble Promastigote Exogenous Antigens in BALB/c Mice. Am J Trop Med Hyg. 2007;76(3):579-84.
Dar MJ, McElroy CA, Khan MI, Satoskar AR, Khan GM. Development and Evaluation of Novel Miltefosine-Polyphenol Co-Loaded Second Generation Nano-Transfersomes for the Topical Treatment of Cutaneous Leishmaniasis. Expert Opin Drug Deliv. 2020;17(1):97-110.
World Health Organization. Research Priorities for Chagas Disease, Human African Trypanosomiasis and Leishmaniasis. World Health Organization; 2012.
Saurabh S. Leishmaniasis. The Lancet. 2019;393(10174):871.
Fanti JR, Tomiotto-Pellissier F, Miranda-Sapla MM, Cataneo AHD, de Jesus Andrade CGT, Panis C, et al. Biogenic Silver Nanoparticles Inducing Leishmania Amazonensis Promastigote and Amastigote Death In Vitro. Acta Trop. 2018;178:46-54.
Herwaldt BL, Berman JD. Recommendations for Treating Leishmaniasis with Sodium Stibogluconate (Pentostam) and Review of Pertinent Clinical Studies. Am J Trop Med Hyg. 1992;46(3):296-306.
Miranda-Verastegui C, Tulliano G, Gyorkos TW, Calderon W, Rahme E, Ward B, et al. First-Line Therapy for Human Cutaneous Leishmaniasis in Peru Using the TLR7 Agonist Imiquimod in Combination with Pentavalent Antimony. PLoS Negl Trop Dis. 2009;3(7).
Espuelas S. Conventional Formulations and Emerging Delivery Systems for the Topical Treatment of Cutaneous Leishmaniasis. Ther Deliv. 2015;6(2):101-3.
Kevric I, Cappel MA, Keeling JH. New World and Old World Leishmania Infections: A Practical Review. Dermatol Clin. 2015;33(3):579-93.
Croft SL, Yardley V. Chemotherapy of Leishmaniasis. Curr Pharm Des. 2002;8(4):319-42.
Barratt G, Bretagne S. Optimizing Efficacy of Amphotericin B Through Nanomodification. Int J Nanomedicine. 2007;2(3):301.
Feng L, Gao M, Tao D, Chen Q, Wang H, Dong Z, et al. Cisplatin-Prodrug-Constructed Liposomes as a Versatile Theranostic Nanoplatform for Bimodal Imaging Guided Combination Cancer Therapy. Adv Funct Mater. 2016;26(13):2207-17.
Awasthi V, Garcia D, Goins B, Phillips W. Circulation and Biodistribution Profiles of Long-Circulating PEG-Liposomes of Various Sizes in Rabbits. Int J Pharm. 2003;253(1-2):121-32.
Kalat SM, Khamesipour A, Bavarsad N, Fallah M, Khashayarmanesh Z, Feizi E, et al. Use of Topical Liposomes Containing Meglumine Antimoniate (Glucantime) for the Treatment of L. Major Lesion in BALB/c Mice. Exp Parasitol. 2014;143:5-10.
Panda S, Swaminathan S, Hyder KA, Christophel E-M, Pendse RN, Sreenivas AN, et al. Drug Resistance in Malaria, Tuberculosis, and HIV in South East Asia: Biology, Programme, and Policy Considerations. BMJ. 2017;358.
Hendrickx S, Van den Kerkhof M, Mabille D, Cos P, Delputte P, Maes L, et al. Combined Treatment of Miltefosine and Paromomycin Delays the Onset of Experimental Drug Resistance in Leishmania Infantum. PLoS Negl Trop Dis. 2017;11(5).
Blum JA, Hatz CF. Treatment of Cutaneous Leishmaniasis in Travelers 2009. J Travel Med. 2009;16(2):123-31.
Bruix J, Qin S, Merle P, Granito A, Huang Y-H, Bodoky G, et al. Regorafenib for Patients with Hepatocellular Carcinoma Who Progressed on Sorafenib Treatment (RESORCE): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet. 2017;389(10064):56-66.
Cleghorn LA, Woodland A, Collie IT, Torrie LS, Norcross N, Luksch T, et al. Identification of Inhibitors of the Leishmania CDC2-Related Protein Kinase CRK3. ChemMedChem. 2011;6(12):2214.
Dar MJ, Din FU, Khan GM. Sodium Stibogluconate Loaded Nano-Deformable Liposomes for Topical Treatment of Leishmaniasis: Macrophage as a Target Cell. Drug Deliv. 2018;25(1):1595-606.
Frézard F, Michalick M, Soares C, Demicheli C. Novel Methods for the Encapsulation of Meglumine Antimoniate Into Liposomes. Braz J Med Biol Res. 2000;33:841-6.
Aggarwal N, Goindi S. Preparation and Evaluation of Antifungal Efficacy of Griseofulvin Loaded Deformable Membrane Vesicles in Optimized Guinea Pig Model of Microsporum Canis—Dermatophytosis. Int J Pharm. 2012;437(1-2):277-87.
Mir-Palomo S, Nácher A, Díez-Sales O, Busó MOV, Caddeo C, Manca ML, et al. Inhibition of Skin Inflammation by Baicalin Ultradeformable Vesicles. Int J Pharm. 2016;511(1):23-9.
World Health Organization. Basic Laboratory Methods in Medical Parasitology. World Health Organization; 1991.
Jaafari MR, Hatamipour M, Alavizadeh SH, Abbasi A, Saberi Z, Rafati S, et al. Development of a Topical Liposomal Formulation of Amphotericin B for the Treatment of Cutaneous Leishmaniasis. Int J Parasitol Drugs Drug Resist. 2019;11:156-65.
Honary S, Zahir F. Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems—A Review (Part 1). Trop J Pharm Res. 2013;12(2):255-64.
Jain S, Jain P, Umamaheshwari R, Jain N. Transfersomes—A Novel Vesicular Carrier for Enhanced Transdermal Delivery: Development, Characterization, and Performance Evaluation. Drug Dev Ind Pharm. 2003;29(9):1013-26.
Cevc G, Schätzlein A, Richardsen H. Ultradeformable Lipid Vesicles Can Penetrate the Skin and Other Semi-Permeable Barriers Unfragmented. Evidence from Double Label CLSM Experiments and Direct Size Measurements. Biochim Biophys Acta Biomembr. 2002;1564(1):21-30.
Avadhani KS, Manikkath J, Tiwari M, Chandrasekhar M, Godavarthi A, Vidya SM, et al. Skin Delivery of Epigallocatechin-3-Gallate (EGCG) and Hyaluronic Acid Loaded Nano-Transfersomes for Antioxidant and Anti-Aging Effects in UV Radiation Induced Skin Damage. Drug Deliv. 2017;24(1):61-74.
Caddeo C, Nacher A, Vassallo A, Armentano MF, Pons R, Fernàndez-Busquets X, et al. Effect of Quercetin and Resveratrol Co-Incorporated in Liposomes Against Inflammatory/Oxidative Response Associated with Skin Cancer. Int J Pharm. 2016;513(1-2):153-63.
Verma DD, Verma S, Blume G, Fahr A. Particle Size of Liposomes Influences Dermal Delivery of Substances Into Skin. Int J Pharm. 2003;258(1-2):141-51.
Khan MA, Pandit J, Sultana Y, Sultana S, Ali A, Aqil M, et al. Novel Carbopol-Based Transfersomal Gel of 5-Fluorouracil for Skin Cancer Treatment: In Vitro Characterization and In Vivo Study. Drug Deliv. 2015;22(6):795-802.
El Zaafarany GM, Awad GA, Holayel SM, Mortada ND. Role of Edge Activators and Surface Charge in Developing Ultradeformable Vesicles with Enhanced Skin Delivery. Int J Pharm. 2010;397(1-2):164-72.
Cevc G. Transfersomes, Liposomes and Other Lipid Suspensions on the Skin: Permeation Enhancement, Vesicle Penetration, and Transdermal Drug Delivery. Crit Rev Ther Drug Carrier Syst. 1996;13(3-4).
Katare O, Raza K, Singh B, Dogra S. Novel Drug Delivery Systems in Topical Treatment of Psoriasis: Rigors and Vigors. Indian J Dermatol Venereol Leprol. 2010;76(6):612.
El Maghraby GM, Barry BW, Williams AC. Liposomes and Skin: From Drug Delivery to Model Membranes. Eur J Pharm Sci. 2008;34(4-5):203-22.
Alving CR. Macrophages as Targets for Delivery of Liposome-Encapsulated Antimicrobial Agents. Adv Drug Deliv Rev. 1988;2(1):107-28.
Owais M, Gupta C. Targeted Drug Delivery to Macrophages in Parasitic Infections. Curr Drug Deliv. 2005;2(4):311-8.
Hillaireau H, Couvreur P. Nanocarriers’ Entry Into the Cell: Relevance to Drug Delivery. Cell Mol Life Sci. 2009;66(17):2873-96.
Baillie A, Coombs G, Dolan T, Laurie J. Non-Ionic Surfactant Vesicles, Niosomes, as a Delivery System for the Anti-Leishmanial Drug, Sodium Stibogluconate. J Pharm Pharmacol. 1986;38(7):502-5.
Bavarsad N, Bazzaz BSF, Khamesipour A, Jaafari MR. Colloidal, In Vitro and In Vivo Anti-Leishmanial Properties of Transfersomes Containing Paromomycin Sulfate in Susceptible BALB/c Mice. Acta Trop. 2012;124(1):33-41.
Gupta PN, Mishra V, Rawat A, Dubey P, Mahor S, Jain S, et al. Non-Invasive Vaccine Delivery in Transfersomes, Niosomes and Liposomes: A Comparative Study. Int J Pharm. 2005;293(1-2):73-82.
Nwaka S, Hudson A. Innovative Lead Discovery Strategies for Tropical Diseases. Nat Rev Drug Discov. 2006;5(11):941-55.
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