Table 2.

In vivo performance of oral BNZ-based nanomedicines.^a

Type nanomedicine/ composition	Physicochemical properties	In vivo assays	Outcome	Ref.
nanocrystals (BNZ-NC) BNZ dispersed in poloxamer 188	63.3 ± 2.82 nm; PDI: 3.35 ± 0.1; −18.30 ± 1.0 mV ζ-potential BNZ-NC dispersed in olive oil for administration	acute model, C3H/HeN mice, Nicaragua strain BNZ: 50 mg/kg/day for 15 days (750 mg/kg TD) BNZ-NC: 50, 25, and 10 mg/kg/day for 30 days (1500, 750, and 300 mg/kg TD, respectively) and 50 and 25 mg/kg/day for 15 days (750 and 375 mg/kg TD, respectively)	without treatment 15% survival at 50 dpi with BNZ and BNZ-NC 100% survival	[50]
BNZ-NC same formulation as in [50]		acute model, C3H/HeN mice, Nicaragua strain infected + immunosuppression (60 dpi) BNZ: 50 mg/kg/day for 30 days (1500 mg/kg TD) BNZ-NC:10, 25, and 50 mg/kg/day for 30 days (300, 750, and 1500 mg/kg TD, respectively) starting 2 dpi.	without treatment 15% survival BNZ and BNZ-NC survived until 92 dpi	[49]
BNZ-NC same formulation as in [50]		chronic model, C57BL/6J mice, Nicaragua strain BNZ: 50 and 75 mg/kg/day for 30 days (1500 and 2250 mg/kg TD, respectively) or 13 times one dose every seven days (it) of 75 or 100 mg/kg (975 and 1300 mg/kg TD, respectively) BNZ-NC: 25 and 50 mg/kg/day for 30 days (750 and 1500 mg/kg TD, respectively) or 13 times one dose every seven days (it) of 50 and 75 mg/kg/day (650 and 975 mg/kg TD, respectively) starting 90 dpi	All infected mice survived (210 dpi). Untreated mice median parasite load 8.9 Eq/mL BNZ (75 mg/kg × 30 days) and BNZ (it) 100, showed 80% and 75% without parasitaemia, respectively BNZ-NC (it) 50, 80% negative qPCR no parasite load could be detected in any other BNZ-NC group	[51]
BNZ-SNEDDSs Miglyol®810N, Capryol 90®, Lipoid S75, Labrasol®, N-methyl pyrrolidone (30:15:20:15:20 v/v)	25 mg/mL BNZ; 500 nm	acute model, BALB/c mice, Y strain 100 mg/kg/day starting 4 dpi for 20 days	57% cure for both free-BNZ and BNZ-SEDDSs groups	[52]
BNZ-NFX-SNEDDSs Labrasol, Labrafil 1944CS, Capryol 90 50.00:10.12:39.88 (w/w)	132 ± 7 nm; PDI: 0.610 ± 0.056; 33.1 ± 2.4 mV ζ-potential	acute model, BALB/c mice, Y strain. NFX (50 mg/kg/day) or BNZ (50 mg/kg/day) orally daily for 5 days NFX-BNZ-SNEDDSs (25 and 50 mg/kg/day), BNZ-SNEDDSs (50 and 100 mg/kg/day) administered orally once a day for five consecutive days starting 5 dpi	without treatment 15–17.5 days survival NFX and BNZ increase survival to 30 dpi	[53]
NCP Eudragit L100 (0.25 g), BNZ (0.025 g), sorbitan monooleate (0.19 g), medium-chain triglycerides (413 μL), ethanol (67 mL), and aqueous phase (polysorbate 80 (0.19 g) and water))	146 ± 0.6 nm; PDI: 0.15 ± 0.01; −12.8 ± 0.87 mV ζ-potential; EE: 96%	acute model, Swiss mice, Y strain BNZ-NCP 5, 10, 15, and 20 mg/kg/day starting 2 dpi for eight days	BNZ (100 mg/kg/day) reduced parasitemia and 100% survival after 30 days	[54]

^aAbbreviations: NCP – nanocapsules, IV – intravenous, it – intermittent.