. 2021 Mar 10;11(3):689. doi: 10.3390/nano11030689

Table 1.

A list of in vitro studies of chitosan and its derivatives as resource for anti-leishmanial agents.

Type of Chitosan	Combined with the Drug	Year of Publication	Parasite Form	Leishmania spp.	Concentration	Time	Outcome	Ref.
AmB-loaded pluronic F127 (PF 127) micelles coated with chitosan (Cs-PF-AmB-M)	Amphotericin B (AmpB)	2017	Promastigotes	Leishmania donovani	0.03, 0.05, 0.1, 0.2, 0.4, 0.8 µg/mL	72 h	Experiments have shown that Cs-PF-AmB-M at a dose of 0.049 µg/mL may reduce parasitic load by 50%; whereas PF-AmB-M at a dose of 0.08 µg/mL reduced parasitic load by 50%.	[30]
Chitosan	-	2018	Promastigotes	L. major	50, 100, 200, 400 μg/mL	30, 60, 120 and 180 min	The results showed that chitosan at the concentrations of 200 and 400 μg/mL after 180 min killed 100% of promastigote.	[31]
Chitosan-based silver nanoparticles	-	2017	Promastigotes and amastigotes	L. amazonensis	0.42 to 27µg	48 h	The results showed that this compound has potent anti-leishmanial effects against promastigote and amastigote stages of L. amazonensis after 48 h exposure, with IC₅₀ values ranging from 0.422 to 2120 μg/mL.	[32]
Chitosan microparticles	Doxorubicin hydrochloride (DOX)	2011	Promastigotes	L. donovani	0.03, 0.08, 0.13 and 0.2 mg/mL	20 h	The results showed that the greatest effect of these microparticles was in the first 60 min and caused nonspecific activation of phagocytosis in macrophages.	[33]
Chitosan anchored nanostructured lipid carriers (NLC)	Miltefosine (HePC- hexadecyl phosphocholine) and amphotericin B (AmB)	2017	Amastigotes	L. donovani	50, 100, 250, 500, 1000 ng/mL	4 h	The results showed that the highest effect of these nanoparticles was at a concentration of 1000 ng/mL, which killed more than 80% of amastigotes, while AmB alone reduced the parasitic load by about 60%.	[34]
Chitosan nanocapsules containing essential oil of Matricaria chamomilla (NCEO)	-	2020	Promastigotes	L. amazonensis	0.1–1000 μg/mL	48 h	The results showed that IC₅₀ NCEO was 7.18 ± 0.7 μg/mL against promastigotes and 14.29 ± 1.01 μg/mL against amastigotes.	[35]
Chitosan nanoparticles (CNPs) and, 4-SO4GalNAc modified chitosan nanoparticles (SCNP)	Amphotericin B (AmpB)	2015	Amastigotes	L. donovani	0.05, 0.1, 0.2. 0.4. 0.8 (µg/mL)	24 h	The results showed that AmB-SCNPs and AmB–CNPs had a better effect in comparison with amphotericin B and more than 80% of their lethality was recorded, while for amphotericin B 70% lethality have been recorded.	[36]
Chitosan nanoparticles	-	2019	Amastigotes	L. major	5–250 µL/mL	48 h	Chitosan coupled with L. major secretory and excretory proteins can increase the ability of infected macrophages to remove parasites by reducing apoptosis.	[37]
Chitosan nanoparticles	Miltefosine	2020	Promastigotes and amastigotes	L. tropica	100 µL/mL	72 h	The results showed that IC₅₀ value for promastigote and amastigote forms of L. tropica was 0.07 ± 0.05 µL/mL and 0.09 ± 0.02 µL/mL, respectively,	[38]
Chitosan nanoparticles and sodium tripolyphosphate (TPP)	Amphotericin B (AmB)	2020	Amastigotes	L. major and L. mexicana	1 mg/mL	7 days	The results showed that EC₅₀ value of AmB-CH-TPP for L. major and L. mexicana amastigotes was 0.14 ± 0.09 µg/mL and 0.5 ± 0.01 µg/mL, respectively.	[39]
Chitosan-polyethylene oxide nanofibers containing berberine	-	2020	Promastigotes and amastigote	L. major	0.01–50 μg/mL	24, 48, 72 h	The results showed that this compound has potent anti-leishmanial effects against promastigotes and amastigotes of L. major with IC₅₀ values ranging from 0.197 to 1.023 μg/mL.	[40]
Curcumin-loaded mannose-functionalized chitosan nanoparticles (Cur-MCN)	-	2018	Amastigotes	L. donovani	0.05–2.0 mg/L	72 h	The results showed that Cur-MCN at the concentration of 0.518 ± 0.01 mg/L reduced 50% of amastigotes; also, no toxic effect on macrophages was observed in the use of Cur-MCN.	[41]
Encapsulate S-nitroso-mercaptosuccinic acid into chitosan nanoparticles (NONPs)	-	2019	Promastigotes and amastigotes	L. amazonensis	25, 50, 75, 100, 200, 400 µM	24 h	Experiments on amastigotes and promastigotes of L. amazonensis showed that NONPs reduced 65% of the parasitic load at a dose of 200 µM and killed 85% of promastigotes at a dose of 75 µM. These nanoparticles also reduced the number of amastigotes from 8.5 ± 1.2 in the control group to 4.5 ± 0.4 per 300 macrophages and reduced the infection rate from 76.2 ± 7.1 to 63.7 ± 5.4.	[42]
Mannosylated chitosan (MCS) with dextran (dex)	Paromomycin (PM)	2019	Amastigotes	L. major	5, 10, 20, 40, 80, 160, 320 μg/mL	24, 48 h	The results showed that this compound has no cytotoxicity on macrophages and at a dose of 5 μg/mL reduced more than 60% of the parasitic load inside macrophages.	[43]
Nanosized chitosan-betulinic acid	-	2020	Promastigotes and amastigote	L. major	20 μg/mL	48 h	The results showed that BK20 (20 μg/mL) was effective to kill the parasite by 86% compared to negative control group. The infection rate and the mean number of amastigotes per each macrophage were found to be 73% and 7%, respectively.	[44]
Oleoyl chitosan and α-cyclodextrin (α-CD)	-	2019	Amastigotes	L. major	100 μL	4 days	The results showed that the use of oleoyl chitosan/α-CD platelets at a dose of 60.24 ± 4.42 μg/mL killed 50% of amastigotes.	[45]
Poly (isobutylcyano acrylate) nanoparticles coated with chitosan (Cs-NPs)	Amphotericin B-deoxycholate (AmB-DOC)	2019	Promastigotes and amastigote	L. major	20 mg/mL	10 min, 20 min, 30 min, 1 h, or 2 h	The IC₅₀ values for L. major promastigote and axenic amastigote forms were 1.14 ± 0.11 μg/mL and 0.53 ± 0.07 μg/mL, respectively.	[46]
Sodium alginate-glycol chitosan stearate nanoparticles (SA-GCS-NP)	Amphotericin B (AmB)	2015	Amastigotes	L. donovani	10 ng/mL	48 h	The IC₅₀ values of AmB-SAGCS-NP and AmB for amastigotes of L. donovani were 0.128 ± 0.024 μg/mL and 0.214 ± 0.06 μg/mL, respectively.	[47]