Amphotericin B-loaded polymeric nanoparticles: formulation optimization by factorial design.

In this study, PLGA or PLGA-PEG blend nanoparticles were developed loading amphotericin B (AmB), an antifungal agent broadly used in therapy. A 2(2) × 3(1) factorial experimental design was conducted to indicate an optimal formulation of nanoparticles containing AmB and demonstrate the influence of the interactions of components on the mean particle size and drug encapsulation efficiency. The independent variables analyzed were polymer amount (two levels) and organic phase (three factors in one level). The parameters methanol as cosolvent and higher polymer amount originated from the higher AmB encapsulation, but with the larger particle size. The selected optimized parameters were set as the lower polymer amount and ethyl acetate as cosolvent in organic phase, for both PLGA and PLGA-PEG nanoparticles. These parameters originated from nanoparticles with the size of 189.5 ± 90 nm and 169 ± 6.9 nm and AmB encapsulation efficiency of 94.0 ± 1.3% and 92.8 ± 2.9% for PLGA and PLGA-PEG nanoparticles, respectively. Additionally, these formulations showed a narrow size distribution indicating homogeneity in the particle size. PLGA and PLGA-PEG nanoparticles are potential carrier for AmB delivery and the factorial design presented an important tool in optimizing nanoparticles formulations.

Poly(L-lactide) Nanoparticles Reduce Amphotericin B Cytotoxicity and Maintain Its In Vitro Antifungal Activity.

In this study, poly(L-lactide) (PLA) nanoparticles containing amphotericin B (AmB) were developed, and the in vitro cytotoxicity to human erythrocytes and efficacy on strains of Candida spp. were evaluated. The nanoparticles were prepared using an emulsion/solvent evaporation method and were characterized with respect to size, size distribution, AmB encapsulation efficiency, AmB state of aggregation, and AmB in vitro release profile. The mean particle size was 225 nm, and the AmB encapsulation efficiency was over 69%. The AmB in vitro release profile revealed a burst effect within the first 24 h, which released approximately 10% of AmB, followed by a sustained release of approximately 30% of AmB over 30 days. The AmB nanoparticles presented a very low index of hemolysis compared to free AmB, which lysed more than 80% of erythrocytes in the first 2 h of incubation. The AmB-loaded PLA nanoparticles were as effective as free AmB against strains of Candida spp., considering their sustained release profile. Thus, PLA nanoparticles can deliver AmB with reduced toxicity while maintaining its antifungal activity.