Table 4 Surface modified Nano-DDS for target leishmanial destruction

Chitosan NPs

d-Mannose

Mannose receptor expressed by macrophages

Amphotericin-B

In vitro

(L. donovani infected J744 macrophages)

In vivo (BALB/c mice)

Mannosylation has resulted in persistent intramacrophage drug accumulation up to 10 days

The designed mannosylated thiolated system exhibited better internalization and intramacrophage amastigote killing activity as compared to L-Amp-B

[162]

d-Mannose

Mannose receptor expressed by macrophages

Rifampicin

In vitro

Macrophagial internalization of drug-loaded in mannose labeled NPs was observed about 2.31-fold higher than unlabeled chitosan NPs

[168]

d-Mannose

Mannose receptor expressed by macrophages

Paromomycin

In vitro (L. major amastigote infected macrophages)

The strong leishmanicidal response was observed with mannosylated chitosan nanocarrier, owing to its targeting ability-lowest IC₅₀

No toxicity was observed against THP-1 cells-highest CC₅₀

[170]

Thiolated Polyethylenimine NPs

d-Mannose

Mannose receptor expressed by macrophages

Meglumine Antimonate

In vitro (L. tropica infected macrophage)

Mannosylation has resulted in enhanced accumulation of drug inside infected macrophages

Thiolation has resulted in inhibition of P-gp and TR-system

[165]

Nano lipid carriers (NLCs)

d-Mannose

Mannose receptor expressed by macrophages

Rifampicin

In vitro (2447-Mycobacterium avium infected macrophages derived from C57B1/6 B6 mice)

Mannosylated NLCs are more beneficial in terms of bacterial killing as compared to non-mannosylated NLCs and plain drug. Mannosylated NLCs exhibit lower IC₅₀

[166]

Thiolated Chitosan-PLGA NPs

d-Mannose

Mannose receptor expressed by macrophages

Paromomycin

In vitro (L. donovani infected macrophages)

In vivo (BALB/c mice infected with L. donovani)

Simultaneous mannosylation and thiolation was associated with boosted cellular uptake of drug and lower incidence of efflux

Nitric oxide production evaluation also yields the results evidencing its supremacy to non-thiolated and non-mannosylated NPs

[155]

Gelatin NPs

d-Mannose

Mannose receptor expressed by macrophages

Amphotericin-B

In vitro (J74A.1 macrophage cell line infected with L. donovani amastigotes)

Mannosylated gelatin NPs appeared to hold enhanced intramacrophage parasitic inhibition to that of AmBisome®

[171]

PLGA-PEG NPs

CD-14

–

Amphotericin-B

In vitro (L. donovani)

In vivo (Hamsters)

Better splenic parasitic reduction with Amp-B loaded PLGA-PEG CD-14 bio-conjugated NPs as compared to the conventional Amp-B and Liposomal Amp-B

[164]

PLGA NPs

Lactoferrin

Mannose receptor expressed by APCs

Amphotericin-B

In vitro (J744A.1 macrophage cell line infected with L. donovani)

In vivo (Hamsters)

Lactoferrin labeled Amp-B loaded nanocarrier was resulted to have lowest IC₅₀ and the highest percentage of amastigotes execution than rest of the experimental formulations

[167]

Liposomes

Phosphatidylserine

Scavenger receptors (SR) expressed on the surface of macrophages and other APCs

Antimony (Sb)

In vitro (M 6445—L. chagasi

IC₅₀ of liposomal Sb is 16 times lower than that of conventional pentavalent antimony

However, the results of leishmanial infected macrophage drug internalization were not much satisfactory

[172]

Nano-capsules (NCs)

Phosphatidylserine

Scavenger receptors (SR)

Doxorubicin

In vitro (J744A.1 macrophage cell line infected with L. donovani)

In vivo (Wister Rats)

Results were satisfactory with 1.75-fold higher APCs internalization, significantly lowered IC_50, and higher distribution in liver and spleen is seen followed by the administration in Wister rats

[173]