Advances in nanocarriers as drug delivery systems in Chagas disease

Figures & data

Figure 1 Nanomaterials used against Chagas disease. Strategies and application of nanocarrier-based drug delivery systems, such as liposomes, micelles, mesoporous silica nanoparticles, polymeric and non-polymeric nanoparticles to optimize the delivery of antitrypanosomal agents.

Table 1 Polymeric and liposomal nanomaterials against Chagas disease in preclinical trials

Nanomaterial	Nanostructure characterization					Biological analysis					Author	Ref #
	Physical and/or chemical methodology	Active compound	Hydrodynamic diameter or size (nm)	ZP (mV)	PDI	T. cruzi strain	Host Cell line	In vitro/in vivo		Administration route
SEDDSs	Self-emulsifying	RAV	100–250	−45–−57	0.20–0.30	Y	Cardiomyocyte (H9c2)	In vivo	Swiss albino mice	Oral	Sposito et al (2017)	^Citation39
In vitro	Amastigotes	N.I.
PACA	Emulsion polymerization	Nifurtimox	<200	N.I.		from chronic patients in northern Chile	Vero	In vitro	Epimastigotes	N.I.	Gonzalez-Martin et al (1998)	^Citation27
Cytotoxicity
Allopurinol	Epimastigotes	Gonzalez-Martin et al (2000)	^Citation29
Amastigotes
PLA-PEG	Simple emulsification	Bis-triazole D0870	100–200	N.I.		CL and Y	N.I.	In vivo	Swiss albino mice	IV	Molina et al (2001)	^Citation30
PCL-PLA-PEG	Nanoprecipitation	LYC	100−250	−30–−57	0.30	N.I		In vivo	C57BL/6 mice	IV	Branquinho, Roy, et al (2017)	^Citation136
NC-PCL-PLA-PEG	Nanoprecipitation	LYC	105.30−105.30	N.I.		CL and Y		In vivo	Swiss albino mice	IV	Branquinho et al (2014)	^Citation40
PN	Nanoprecipitation	UA	173.20	36	0.09	Y	LLC-MK2	In vitro	Cytotoxicity	N.I.	Abriata et al (2017)	^Citation41
In vitro	Trypomastigotes
In vivo	C57BL/6 mice	IV
Polymeric nanoparticles	Ionotropic gelation	Nitric oxide	270–500	N.I.	0.35	Y	Murine peritoneal macrophage	In vitro	Trypomastigotes	N.I.	Seabra et al (2015)	^Citation36
Amastigotes
Multiparticulate benzonidazole polymers	Nanoprecipitation and freezedrying	BNZ	233	35.40	0.10	N.I.					Seremeta et al (2019)	^Citation45
NPs	Nanoprecipitation	BNZ	63.30	18.3	3.35	TcN	Vero	In vitro	Cytotoxicity	N.I.	Rial et al (2017)	^Citation42
In vivo	C3H/HeN mice	Oral
Liposomes	N.I.	Amphotericin B	N.I.			Tulahuen		In vivo	BALB/cJ	IP	Cencig et al (2011)	^Citation59
Y	N.I.										Clemons et al (2017)	^Citation140
CL
Hydration	Stearylamine	Tulahuen		In vitro	Epimastigotes, trypomastigotes and amastigotes	N.I.	Yoshihara et al (1987)	^Citation143
Extrusion	ETZ	379	N.I.			RA	Monocyte macrophage (J774)	In vitro	Amastigotes	N.I.	Morilla et al (2005)	^Citation52
	In vivo	BALB/c mice	IV
MLV	Hydration	BNZ	2000	N.I.		RA		In vivo	Wistar rats	IV	Morilla et al (2004)	^Citation50

Abbreviations: BNZ, Benznidazole; mv, millivolt; IV, Intravenous injection; PACA, Poly (alkyl cyanoacrylate) nanoparticles; TcN, Nicaragua Strain; nps, Nanoparticles; PN, Nanoparticles with poly-Ɛ-caprolactone; NC, Nanocapsules; PCL, Poly-ε-caprolactone; PLA-PEG, polyethylene glycol-polylactide; ZP, Zeta potential; PDI, Polydispersity index; RAV, Ravuconazole; SEDDSs, Self-emulsifying drug delivery systems; Vero, Fibroblast of African green monkey kidney; LL-MK2, Fibroblast of monkey kidney; LYC, Lychnopholide; UA, Ursolic acid; N.I. not informed; RAS strain, pantropic/reticulotropic; T. cruzi, Trypanosoma cruzi.

Figure 2 Hypothetical mechanisms of the internalization of pH-sensitive liposomes.

Table 2 Other types of nanomaterials against Chagas disease in preclinical trials

Nanomaterial		Nanostructure characterization					Biological analysis					Author	Ref #
Physical and/or chemical methodology	Active compound	Hydro- dynamic diameter or size (nm)	ZP (mV)	PDI	T. cruzi strain	Cell line	In vitro/in vivo	Study model	Adminis-tration route
SLN		Microemulsion	H2bdtc	127.4	−56.1	0.3	Y	Spleen cells of Swiss mice	In vitro	Trypomastigotes	N.I.	Carneiro et al (2014)	^Citation67
N.I.	In vivo	Swiss mice	Oral
Quantum dots		Colloidal chemistry	Cd Te	N.I.			Dm28	Intestinal epithelial cells of R. prolixus	In vitro	Epimastigotes	N.I.	Stahl et al (2010)	^Citation81
Nano-emulsions; sulfonamides		Emulsification	Ursolic acid	57.3	N.I.	0.24	CL Brener	LLC-MK2	In vitro	Cytotoxicity	N.I.	De Oliveira et al (2017)	^Citation86
In vitro	Amastigotes
Clove oil (Eugenia caryophyllus)	35 −100	0.3	DM28c and Y	Macrophages (RAW 267.4)	In vitro	Epimastigotes	Vermelho et al (2017)	^Citation87
In vitro	Cytotoxicity
		BZ	241.60	−71.41	0.23	Y	Vero and SiHa	In vitro	Cytotoxicity	N.I.	Streck et al (2019)	^Citation88
In vitro	Epimastigotes and trypomastigotes
Micelle; poly-agrregate		AmB-AME	Amphotericin B	1–10 x10^3	N.I.		Clone CL- B5	Fibroblasts (NCTC-929)	In vitro	Amastigotes	N.I.	Rolon et al (2017)	^Citation95
AmB-NaDC	30	Y	In vivo	BALB/c	Intracardiac
Mesoporous silica nanoparticles		Hydration	BNZ	N.I.	−11.5	N.I.	CL Brener	N.I.	In vitro	Epimastigotes	N.I.	Nhavene et al (2018)	^Citation74

Abbreviations: PDI, Polydispersity index; ZP, Zeta potential; SLN, Solid Lipid Nanoparticles; H2bdtc, 5-hydroxy-3-methyl-5-phenyl-pyrazoline-1- S-Benzyl dithiocarbazate; CdTe, Cadmium telluride solution; AMB, amphotericin B liposomes; AmB-AME, amphotericin B liposomes - polyamide encapsulated in albumin microspheres; AmB-NaDC, Dimeric amphotericin B liposomes - sodium deoxycholate micelles; N.I. not informed; BNZ, Benznidazole; LLC-MK2, Fibroblast of monkey kidney.

Figure 3 Chunap assay for the early diagnosis of congenital Chagas disease. Chunap (Chagas urine nanoparticle assay) is to perform an early and non-invasive diagnosis for congenital Chagas disease, by concentrating, preserving and detecting antigens secreted/excreted by trypomastigote forms (TESA) from urine by Western Blot.

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