Paromomycin-loaded mannosylated chitosan nanoparticles: Synthesis, characterization and targeted drug delivery against leishmaniasis

[Display omitted] •CS was mannosylated and its nanoparticles were prepared by ionic gelation.•PM was loaded into MCS nanoparticles as a new formulation.•THP-1 cell cytotoxicity, and promastigotes and amastigotes viabilities of the formulation were evaluated in vitro.•The results were compared with a PM aqueous solution. Cutaneous leishmaniasis is the most common form of leishmaniasis caused by different species of Leishmania parasites. The emergence of resistance, toxicity, long term treatment, high cost of the current drugs, and intracellular nature of the parasite are the major difficulties for the treatment of leishmaniasis. Although the therapeutic effect of paromomycin (PM) on leishmaniasis has been investigated in different studies, it has a low oral absorption and short half-life, leading to a decreased drug efficacy. Therefore, new and targeted carriers with no such problems are needed. In the present study, PM was loaded into chitosan (CS) nanoparticles accompanied by targeting to macrophages (as the host of Leishmania parasite). PM-loaded into mannosylated CS (MCS) nanoparticles using dextran (PM-MCS-dex-NPs) was prepared by ionic gelation and then characterized. The particle size and zeta potential of PM-MCS-dex-NPs were obtained as 246 nm and +31 mV, respectively. Mannosylation of CS was qualitatively evaluated by Fourier-transform infrared spectroscopy and quantitatively measured by CHNO elemental analysis; also, a mannosylation level of 17% (w) was attained. Encapsulation efficiency (EE), drug release profile, and THP-1 cell uptake potential were determined. A value of 83.5% for EE and a higher release rate in acidic media were achieved. THP-1 cell uptake level of PM-MCS-dex-NPs after 6 h was ˜2.8 and ˜3.9 times of non-mannosylated CS nanoparticles (PM-CS-dex-NPs) and PM aqueous solution, respectively. In vitro cell cytotoxicity and promastigote and amastigote viabilities were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Half-maximal inhibitory concentration values toward the THP-1 cells for PM aqueous solution, Glucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs after 48 h were obtained as 1846 ± 158, 1234 ± 93, 784 ± 52 and 2714 ± 126 μg mL−1, respectively. Half-maximal inhibitory concentration values toward the promastigotes for PM aqueous solution, Glucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs after 48 h were obtained as 105.0 ± 14.0, 169.5 ± 9.8, 65.8 ± 7.3 and 17.8 ± 1.0 μg mL−1, respectively. Selectivity