Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

The development of an efective oral therapeutics is an immediate need for the control and elimination of visceral leishmaniasis (VL). We exemplify the preparation and optimization of 2-hydroxypropyl-β-cyclodextrin (HPCD) modifed solid lipid nanoparticles (SLNs) based oral combinational cargo system of Amphotericin B (AmB) and Paromomycin (PM) against murine VL. The emulsion solvent evaporation method was employed to prepare HPCD modifed dual drugloaded solid lipid nanoparticles (m-DDSLNs).

The optimized formulations have a mean particle size of 141 ± 3.2 nm, a polydispersity index of 0.248 ± 0.11 and entrapment efciency for AmB and PM was found to be 96% and 90% respectively. The morphology of m-DDSLNs was confrmed by scanning electron microscopy and transmission electron microscopy. The developed formulations revealed a sustained drug release profle upto 57% (AmB) and 21.5% (PM) within 72 h and were stable at both 4 °C and 25 °C during short term stability studies performed for 2 months. Confocal laser scanning microscopy confrmed complete cellular internalization of SLNs within 24 h of incubation. In vitro cytotoxicity study against J774A.1 macrophage cells confrmed the safety and biocompatibility of the developed formulations.

Further, m-DDSLNs did not induce any hepatic/renal toxicities in Swiss albino mice. The in vitro simulated study was performed to check the stability in simulated gastric fuids and simulated intestinal fuids and the release was found almost negligible. The in vitro anti-leishmanial activity of m-DDSLNs (1 µg/ml) has shown a maximum percentage of inhibition (96.22%) on intracellular amastigote growth of L. donovani. m-DDSLNs (20 mg/kg× 5 days, p.o.) has signifcantly (P< 0.01) reduced the liver parasite burden as compared to miltefosine (3 mg/kg× 5 days, p.o.) in L. donovani-infected BALB/c mice. This work suggests that the superiority of as-prepared m-DDSLNs as a
promising approach towards the oral delivery of anti-leishmanial drugs.

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Article Information: Parvez Shabi; Yadagiri Ganesh; Rao, Gedda Mallikarjuna; Singh Aakriti; Singh, Om Prakash, Anurag Verma, Shyam Sundar & Shyam Lal Mudavath; Scientific Reports (Nature Publisher Group), 2020.