Amphotericin B is an antibiotic used in the treatment of fungal disease and leishmania; however, it exhibits side effects to patients, hindering its wider application. Therefore, nanocarriers have ...been investigated as delivery systems for amphotericin B (AMB) in order to decrease its toxicity, besides increase bioavailability and solubility. Amphiphilic copolymers are interesting materials to encapsulate hydrophobic drugs such as AMB, hence copolymers of cashew gum (CG) and l-lactide (LA) were synthesized using two different CG:LA molar ratios (1:1 and 1:10). Data obtained revealed that copolymer nanoparticles present similar figures for particle sizes and zeta potentials; however, particle size of encapsulated AMB increases if compared to unloaded nanoparticles. The 1:10 nanoparticle sample has better stability although higher polydispersity index (PDI) if compared to 1:1 sample. High amphotericin (AMB) encapsulation efficiencies and low hemolysis were obtained. AMB loaded copolymers show lower aggregation pattern than commercial AMB solution. AMB loaded nanoparticles show antifungal activities against four C. albicans strains. It can be inferred that cashew gum/polylactide copolymers have potential as nanocarrier systems for AMB.
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Given its many potential applications, cashew gum hydrophobic derivatives have gained increasing attraction in recent years. We report here the effect of acyl chain length on hydrophobized cashew gum ...derivatives, using acetic, propionic, and butyric anhydrides on self-assembly nanoparticle properties and amphotericin B delivery. Nanoparticles with unimodal particle size distribution, highly negative zeta potential, and low PDI were produced. Butyrate cashew gum nanoparticles presented smaller size (<~100 nm) than acetylated and propionate cashew gum nanoparticles and no cytotoxicity in murine fibroblast cells was observed up to 100 µg/mL for loaded and unloaded nanoparticles. As a proof of concept of the potential use of the developed nanoparticle as a drug carrier formulation, amphotericin B (AmB) was encapsulated and fully characterized in their physicochemical, AmB association and release, stability, and biological aspects. They exhibited average hydrodynamic diameter lower than ~200 nm, high AmB efficiency encapsulations (up to 94.9%), and controlled release. A decrease in AmB release with the increasing of the anhydride chain length was observed, which explains the differences in antifungal activity against Candida albicans strains. An excellent storage colloidal stability was observed for unloaded and loaded AmB without use of surfactant. Considering the AmB delivery, the acyl derivative with low chain length is shown to be the best one, as it has high drug loading and AmB release, as well as low minimum inhibitory concentration against Candida albicans strains.
Thermo responsive copolymers were synthesized by radical polymerization of the N-isopropylacrylamide (NIPAm) onto galactomannan (GM) chain. All copolymers showed thermal responsiveness and a critical ...aggregation concentration (CAC) at 25 °C greater than at 50 °C. Below the lower critical solution temperature (LCST), copolymer nanoparticles presented sizes between 16 and 50 nm, whereas above LCST, they aggregate, presenting sizes in the range 145.8–194.0 nm, depending on NIPAm/GM molar ratio. Amphotericin-B (AmB) was encapsulated in the copolymer nanoparticles with encapsulation efficiency of 41.4 ± 2.76% and 69.0 ± 2.92% respectively for CP1 and CP2. In vitro AmB delivery from the CP1 nanoparticles was found to exhibit controlled release profile. Hemolysis assay was carried out using erythrocytes cells and samples of AmB loaded copolymer nanoparticles (CP1-AmB), unloaded copolymer nanoparticles (CP1) and commercial AmB were evaluated. Unloaded copolymer nanoparticles show hemocompatibility while the percentage of hemolysis of erythrocytes cells for CP1-AmB sample was 8.7 times lower than that observed for commercial AmB. CP1-AmB showed similar minimum inhibitory concentration (MIC) as commercial AmB, in four Candida albicans strains. As CP1-AmB nanoparticle show better hemocompatibility than commercial AmB, this thermo responsive copolymer shows potential as AmB nanocarrier device to be used in fungal infection.
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