Paromomycin-Loaded Mannosylated Chitosan Nanoparticles: Targeted Drug Delivery Against BALB/c Mice Infected To L.Major
Abstract Cutaneous leishmaniasis (CL) is a disease with unsatisfactory current therapies due to the emergence of drug resistance and toxicity. Paromomycin (PM), though recently have received more attention for its anti-Leishmania activity, suffers from poor oral bioavailability, limited efficacy and rapid clearance in parenteral route. In this study, we examined the efficacy of nanoparticle-based PM delivery system in treating the murine model infected with Leishmania major (L. major). Paromomycin was loaded in mannosylated chitosan-dextran nanoparticles (PM-MCS-dex-NPs) through ionic gelation method. The particle size and zeta potential of PM-MCS-dex-NPs were obtained as 246 nm and +31 mV, respectively. PM-MCS-dex-NPs effectively affected both stages of the parasite especially the amastigote one in vitro culture. Nanoformulation injected intramuscularly into mice for up to 21 days. Lesion sizes were measured before the onset of treatment and at weekly intervals for a month. In addition, the DNA copy number was quantified in the infected mice by a real time quantitative polymerase chain reaction (qPCR). In vivo results showed that the administration of PM-MCS-dex-NPs with a dose of 10 mg/kg/twice daily significantly reduced the lesion size and DNA copy number compared to the other treatment methods. Lesions sizes in both control groups of chitosan nanoparticles (CS-NPs) and mannosylated nanoparticles (MCS-NPs) were also significantly (p < 0.05) decreased in comparison with the untreated control, suggesting the wound healing property of chitosan. PM-MCS-dex-NPs proved as a promising candidate in delivering PM by boosting the drug solubility and targeting the infected macrophage cells. The results of this study can provide a new and efficient drug delivery system for CL treatment.