Itraconazole encapsulated PLGA‐nanoparticles covered with mannose as potential candidates against leishmaniasis

Abstract

Leishmaniasis is a neglected disease threatening over 350 million people. Antimonials are first-line drugs due to resistance and side effects there is a demand for alternative chemotherapy. Itraconazole (ITZ) is an antimycotic. It was encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and covered with mannose. The NPs were 250 nm and -1.1 mV ± 0.7. PLGA-ITZ-mannose NPs presented a toxicity of 20.7% for J774 cells, and no toxicity for THP 1. The J774 cells were infected with three Leishmania promastigotes strains and treated with ITZ loaded PLGA NPs with/without mannose. The parasite percentage of L.(V.) panamensis intracellular amastigotes significantly (p < 0.01) decreased from 34.4% to 13.7% and 5.7% for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively. For L.(L.) infantum there was a reduction (p < 0.001) from 18.1% to 4.8% and 8.3% for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively. Further with L.(L.) braziliensis amastigotes there was a significant reduction (p < 0.001) from 54.9% to 28% and 21.1% for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively. Adding mannose increased the efficacy PLGA-ITZ NPs against L.(L.) infantum, while it had no effect against L(V.) panamensis and L.(L.) braziliensis amastigotes. We recommend further investigation of PLGA-ITZ-mannose NPs in animal models to evaluate their potential. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000, 2018.

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

“…Many intracellular pathogens evade the host immune response causing disease by residing and replicating inside the host cells, primarily macrophages. One of the main strategies of microorganisms such as bacteria, protozoa and fungi is the manipulation of the organelle “phagosome” involved in phagocytosis, the main mechanism of defense of macrophages [ 10 , 35 , 124 , 177 ]. The phagosome is a degrading organelle developed by the cell to internalize and degrade microbes.…”

“…Besides, the functionalization of PNs with mannose ligands can be accomplished straight forward by the standard carbodiimide coupling chemistry. Studies of nanoencapsulation in mannose-functionalized PCL PNs [ 210 ], amphotericin B encapsulated in CS [ 232 ] and curcumin [ 233 ], itraconazole [ 10 ] and amphotericin B [ 231 ] encapsulated in PLGA have enhanced the killing of intracellular pathogens with respect to the drug encapsulated into non-functionalized PNs and the drug alone. Research on such new formulations hopefully makes them hit the market shortly.…”

“…Encapsulation of drugs into nanoparticles (NP) represents a valuable option to improve drug solubility and biodistribution, prevent undesirable interactions and drug degradation before reaching the target tissues and cells [ 1 ] and non-specific accumulation of drugs in other tissues. In this context, nanoencapsulated drugs hold the potential to increase the efficiency and effectiveness of therapeutic regimens, particularly in drugs with low solubility, short half-life, variable absorption, and undesirable interactions [ 4 , 7 , 8 , 9 , 10 , 11 , 12 ]. Such improvement comes from the reduction of dose and drug frequencies in patients, which dramatically impact on decreasing both toxic and side effects that drugs usually have intrinsically.…”

“…In recent years, a large number of drug delivery systems have been described in many medical areas, including intracellular infections [ 3 , 5 , 7 , 8 , 10 , 18 , 29 , 30 , 33 ]. Indeed, the global infectious disease therapeutics market size was valued at $46.88 billion in 2018 and is estimated to reach $64.5 in 2023 [ 34 ].…”

Functional Nanocarriers for Delivering Itraconazole Against Fungal Intracellular Infections

“…This fungus, together with Pneumocystis spp, is currently associated with the development of coinfections in HIV-positive patients, whose presence in some geographical regions is even higher than that of bacteria such as M. tuberculosis ( Agudelo et al, 2012 ; Caceres et al, 2018 ; Carreto-Binaghi et al, 2019 ). By encapsulating ITZ in NPs, we expect to reduce the limitations related to its high lipophilicity and low absorption ability ( Ling et al, 2016 ; Alhowyan et al, 2019 ; Biswaro et al, 2019 ). ITZ nanoformulations include nanocrystals ( Wan et al, 2018 ), NPs ( Alhowyan et al, 2019 ; Jana et al, 2019 ), and solid lipid nanoparticles ( Kim et al, 2010 ), among others ( Hong et al, 2006 ; Chen et al, 2008 ; Sharma et al, 2016 ; Karashima et al, 2017 ).…”