Meglumine Antimoniate‐Loaded Aqueous‐Core PLA Nanocapsules: Old Drug, New Formulation against Leishmania‐Related Diseases

Abstract

Leishmaniasis is a human and animal disease endemic in tropical and subtropical areas treated by means of pentavalent antimony as first-line approach. Unfortunately, the formulations available on the market are characterized by significant side effects and a total remission of the disease is difficult to be obtained. The aim of this investigation is to describe the development and characterization of aqueous-core poly-l-lactide (PLA) nanocapsules containing glucantime (meglumine antimoniate, MA) with the aim of increasing the pharmacological efficacy of the active compound. The polymeric systems characterized by a mean diameter of ≈300 nm exert a great interaction with murine macrophages. MA-loaded PLA nanocapsules show a great antileishmanial activity on mice infected with Leishmania infantum with respect to the free drug, favoring a decrease of the administration times. The biodistribution profiles demonstrate a lower renal accumulation of MA after its nanoencapsulation and a significant increase of its plasmatic half-life. The parasite load evaluated by immunohistochemistry shows a significant decrease in liver, spleen, and kidneys when mice are treated with MA-loaded PLA nanocapsules especially after 45 days. The obtained results demonstrate the potential application of MA-loaded PLA nanocapsules as novel nanomedicine for the treatment of leishmaniasis.

Effect of Local Administration of Meglumine Antimoniate and Polyhexamethylene Biguanide Alone or in Combination with a Toll-like Receptor 4 Agonist for the Treatment of Papular Dermatitis due to Leishmania infantum in Dogs

“…Finally, Horoiwaone et al (2020) tested the local application of meglumine antimoniate contained in maltodextrin polymeric colloidal nanocarriers in a murine leishmaniasis model, which showed similar efficacy to the intraperitoneal injection regarding parasite titer reduction and superior healing activity in terms of collagen area deposition [ 47 ]. Other delivery systems have also been tested for systemic administration of meglumine antimoniate, which could be considered for topical administration in future studies, including polymeric nanoformulations such as aqueous-core poly-L-lactide nanocapsules, which have shown a great antileishmanial activity on mice infected with L. infantum [ 48 ]. In addition, this new formulation promotes meglumine antimoniate uptake within the macrophages, increasing its efficacy and decreasing its cellular-negative outcome [ 48 ].…”

“…Other delivery systems have also been tested for systemic administration of meglumine antimoniate, which could be considered for topical administration in future studies, including polymeric nanoformulations such as aqueous-core poly-L-lactide nanocapsules, which have shown a great antileishmanial activity on mice infected with L. infantum [ 48 ]. In addition, this new formulation promotes meglumine antimoniate uptake within the macrophages, increasing its efficacy and decreasing its cellular-negative outcome [ 48 ].…”

Influence of the Dispersion Medium and Cryoprotectants on the Physico-Chemical Features of Gliadin- and Zein-Based Nanoparticles

“…Moreover, the morphology of the zein and gliadin-based nanosystems prepared in the different polar media was investigated using transmission electron microscopy (TEM), as previously reported [37].…”

Aqueous core epigallocatechin gallate PLGA nanocapsules: characterization, antibacterial activity against uropathogens, andin vivoreno-protective effect in cisplatin induced nephrotoxicity

“…An ultrasonic probe sonication (Cole-Parmer Model 50 Cp T 4710 Series, Vernon Hills, IL) was adjusted at 40% of its highest power in an ice bath, EGCG (10 mg) (Zhang et al, 2020 ) aqueous solution was added to DMF organic phase (2 mL) containing PLGA, oleic acid, and span 80 (Cosco et al, 2015 ) ( Table 1 ), then sonicated for 2 min. The primary emulsion was resonicated in an aqueous (5 mL) solution containing Tween 80 (Cosco et al, 2021 ) and PVA ( Table 1 ). The nanodispersion was agitated for three hours to evaporate DMF, and the obtained EGCG-PLGA NCs were washed three times with distilled water using Hettich Microliter Centrifuge MIKRO 220 (Kirchlengern, Germany) at –4 °C and 15 × 10 3 rpm for 20 min per cycle.…”