The use of nanocarriers in drug delivery has provided new opportunities in topical treatment of diseases affecting the skin and mucosa by improving drug permeation and accumulation in the various skin strata, reducing systemic side effects and enhancing the solubility of poorly soluble drugs. The present study aimed to evaluate the application of amphotericin-B loaded nanostructured lipid carriers (AmB-NLCs) for topical treatment of cutaneous leishmaniasis and vulvovaginal candidiasis. AmB-NLCs were characterized for particle size, zeta potential, polydispersity index and encapsulation efficiency. The surface morphology of AmB-NLCs was evaluated using scanning electron microscopy and Fourier transform infrared spectroscopy was done to check chemical interactions between excipients.Thermal properties of prepared AmB-NLCs were evaluated using differential scanning calorimetry. The AmB-NLCs were further characterized for in vitro drug release, ex vivo skin permeation and deposition before evaluating their in vitro and in vivo antileishmanial and antifungal efficacy. Significant accumulation in the skin (22.7 ± 2.6%) supported the topical application potential. Encapsulation of AmB in NLCs resulted in enhanced in vitro potency against various Leishmania and fungal strains as compared to the plain AmB solution. Topical application of AmB-NLCs on L. major infected BALB/c mice resulted in a significant reduction in parasite load compared to the control group. Topical AmB-NLCs gel demonstrated superior efficacy in the vaginal Candida albicans rat model as compared to plain AmB gel. In conclusion, NLCs may have promising potential as carrier for topical treatment of various conditions of skin and mucosa.

Aim: This research aims to identify important formulation parameters for the enhancement of nanoparticle (NP) uptake and decreasing the cytotoxicity in macrophages. Materials & methods: Fluorescent poly(lactic-co-glycolic acid) (PLGA) nanocarriers were characterized for size distributions, zeta potential and encapsulation efficiency. Incubation time, size class, PLGA derivative and chitosan derivative were assessed for uptake kinetics and cell viability. Results: The major determining factor for enhancing cellular uptake were chitosan coatings, combined with acid-terminated PLGA and small NP size. Moreover, cytotoxicity was more favorable for small, chitosan glutamate-coated, acid-terminated PLGA NPs compared with its plain chitosan-coated counterparts. Conclusion: Chitosan glutamate has been shown to be a valuable alternative coating material for acid-terminated PLGA NPs to efficiently and safely target macrophages.

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This research aims to evaluate different-sized nanoparticles consisting of (polyethylene glycol) (PEG) poly(lactic-co-glycolic acid) (PLGA), loaded with fluorescein isothiocyanate for nanoparticle uptake and intracellular fate in sialoadhesin-expressing macrophages, while being functionalized with anti-sialoadhesin antibody. Sialoadhesin is a macrophage-restricted receptor, expressed on certain populations of resident tissue macrophages, yet is also upregulated in some inflammatory conditions. The nanocarriers were characterized for nanoparticle size (84–319 nm), zeta potential, encapsulation efficiency, and in vitro dye release. Small (86 nm) antibody-functionalized PEG PLGA nanoparticles showed persisting benefit from sialoadhesin-targeting after 24 h compared to the control groups. For small (105 nm) PLGA nanoparticles, uptake rate was higher for antibody-conjugated nanoparticles, though the total amount of uptake was not enhanced after 24 h. For both plain and functionalized small-sized (PEG) PLGA nanoparticles, no co-localization between nanoparticles and (early/late) endosomes nor lysosomes could be observed after 1-, 4-, or 24-h incubation time. In conclusion, decorating (PEG) PLGA nanocarriers with anti-sialoadhesin antibodies positively impacts macrophage targeting, though it was found to be formulation-specific.

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