Nanospheres Encapsulating Anti-Leishmanial Drugs for Their Specific Macrophage Targeting, Reduced Toxicity, and Deliberate Intracellular Release

Abstract

The current work focuses on the study of polymeric, biodegradable nanoparticles (NPs) for the encapsulation of doxorubicin and mitomycin C (anti-leishmanial drugs), and their efficient delivery to macrophages, the parasite's home. The biodegradable polymer methoxypoly-(ethylene glycol)-b-poly (lactic acid) (MPEG-PLA) was used to prepare polymeric NPs encapsulating doxorubicin and mitomycin C. The morphology, mean diameter, and surface area of spherical NPs were determined by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and BET surface area analysis. X-ray diffraction was performed to validate drug encapsulation. An in vitro release profile of the drugs suggested a fairly slow release. These polymeric NPs were efficiently capable of releasing drug inside macrophages at a slower pace than the free drug, which was monitored by epi-fluorescence microscopy. Encapsulation of doxorubicin and mitomycin C into NPs also decreases cellular toxicity in mouse macrophages ( J774.1A).

PEGylated Dendritic Polyglycerol Conjugate Delivers Doxorubicin to the Parasitophorous Vacuole in Leishmania infantum Infections

“…The acid‐sensitive PG‐DOX(pH)‐PEG conjugate was less toxic to both; fourfold lower to RAW 264.7 macrophage cell line (CC 50 7.42 ± 0.41 µm) and twofold lower to J774A.1 monocyte macrophage cell line (with CC 50 2.81 ± 0.24 µm). A similar drug toxicity reduction was reported in J774A.1 macrophages using DOX encapsulated in a biodegradable polymer methoxypoly‐(ethylene glycol)‐b‐poly(lactic acid) …”

“…This lower uptake rate in RAW 264.7 macrophages may justify the lower toxicity (fourfold) for this cell line (see Figure B) after 96 h of PG‐DOX(pH)‐PEG treatment compared to J774A.1 macrophages (Figure A). A similar delay in DOX uptake was reported in J744.1A macrophages after treatment with a PEG‐coated biodegradable poly (lactic acid) (PLA) polymer . This was justified by the release of drug due to conversion of dimeric DOX–DOX to DOX monomer due to the acidic pH of the lysosomal compartment.…”

Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability

“…As demonstrated, VANE generally resulted higher levels of cell viability compared to VPA which may have been due to the controlled‐release property of nanoemulsion as shown in drug release studies. This result was also in accordance with other studies whereby the cytotoxic effects of drugs were reduced by encapsulation of drug within nanocarrier . Concentration of 100 μg/ml of VPA is considered non‐toxic as it exhibited ≥80% of cell viability; hence, it was used in assessing the permeation of VPA, F3 VANE and F4 VANE across in‐vitro BBB layer.…”

“…This result was also in accordance with other studies whereby the cytotoxic effects of drugs were reduced by encapsulation of drug within nanocarrier. [37,38] Concentration of 100 lg/ml of VPA is considered non-toxic as it exhibited ≥80% of cell viability [39] ; hence, it was used in assessing the permeation of VPA, F3 VANE and F4 VANE across in-vitro BBB layer.…”

Leishmaniasis treatment update of possibilities for drug repurposing

“…The encapsulation of Figure 6. Anticancer drugs mitomycin in nanospheres has been a novel approach used to decrease drug toxicity in the host cell and has shown promising results for repositioning strategies (81)(82)(83).…”