Formulation, characterization and in vitro anti-leishmanial evaluation of amphotericin B loaded solid lipid nanoparticles coated with vitamin B12-stearic acid conjugate

• Published in: Materials Science & Engineering C Vol. 117; p. 111279
• Main Authors: Singh, Aakriti, Yadagiri, Ganesh, Parvez, Shabi, Singh, Om Prakash, Verma, Anurag, Sundar, Shyam, Mudavath, Shyam Lal
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01-12-2020; Elsevier BV
• Subjects: Amastigotes; Amphotericin B; Bioavailability; Conjugates; Cyanocobalamin; Drug delivery systems; Encapsulation; Evaporation; Hydrogels; Internalization; Intolerance; Lipids; Materials science; Nanoparticles; Polydispersity; Poverty; Solid lipid nanoparticles; Stearic acid; Toxicity; Tropical diseases; Vector-borne diseases; Visceral leishmaniasis; Vitamin B12; Vitamin B12-stearic acid conjugate; Vitamin B12-stearic acid conjugate; Amphotericin B; Visceral leishmaniasis; Solid lipid nanoparticles
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2020.111279

Despite the advancement of new anti-leishmanials, amphotericin B (AmB) prevails as one of the most potent agent in the treatment of visceral leishmaniasis (VL), a neglected tropical disease affecting mostly poverty ridden and underdeveloped regions of the globe. Nonetheless, many patients display intolerance to parenteral AmB, notably at higher dosages. Also, conventional AmB presents an apparently poor absorption. Therefore, to improve AmB bioavailability and overcome multiple barriers for oral delivery of AmB, we fabricated a promising vitamin B12-stearic acid (VBS) conjugate coated solid lipid nanoparticles (SLNs) encapsulated with AmB (VBS-AmB-SLNs) by a combination of double emulsion solvent evaporation and thermal sensitive hydrogel techniques. VBS-AmB-SLNs showed a particle size of 306.66 ± 3.35 nm with polydispersity index of 0.335 ± 0.08 while the encapsulation efficiency and drug loading was observed to be 97.99 ± 1.6% and 38.5 ± 5.6% respectively. In vitro drug release showed a biphasic release pattern and chemical stability of AmB was ensured against simulated gastrointestinal fluids. Cellular uptake studies confirmed complete internalization of the formulation. Anti-leishmanial evaluation against intramacrophage amastigotes showed an enhanced efficacy of 94% which was significantly (P < 0.01) higher than conventional AmB without showing any toxic effects on J774A.1 cells. VBS-AmB-SLNs could serve as a potential therapeutic strategy against VL.
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•A novel nanoparticulate drug delivery system was developed by a combination of double emulsion solvent evaporation and thermal sensitive hydrogel technique.•The less particle size distribution indicated the homogeneity of synthesized solid lipid nanoparticles with a net neutral charge favouring higher mucus permeating ability, and hence can enhance the oral bioavailability of the drug.•Anti-leishmanial evaluation against intramacrophage amastigotes showed an enhanced efficacy of 94% without showing any toxic effects in in vitro studies.•Demonstrates the potentiality of the formulation to serve as a potential therapeutic strategy against visceral leishmaniasis.