title: Solid lipid nanoparticles containing copaiba oil and allantoin: development and role of nanoencapsulation on the antifungal activity.
abstract: The aim of this work was to develop solid lipid nanoparticles (SLN) containing copaiba oil with and without allantoin (NCOA, NCO, respectively) and to evaluate their antifungal activity. Nanoparticle suspensions were prepared using a high homogenisation technique and characterised by dynamic light scattering, laser diffraction, nanoparticle tracking analysis, multiple light scattering analysis, high-pressure liquid chromatography, pH and rheology. The antifungal activities of the formulations were tested in vitro against the emergent yeasts Candida krusei and Candida parapsilosis, and the fungal pathogens of human skin Trichophyton rubrum and Microsporum canis. The dynamic light scattering analysis showed z-average diameters (intensity) between 118.63 ± 8.89 nm for the nanoparticles with both copaiba oil and allantoin and 126.06 ± 9.84nm for the nanoparticles with just copaiba oil. The D[4,3] determined by laser diffraction showed similar results of 123 ± 1.73 nm for the nanoparticles with copaiba oil and allantoin and 130 ± 3.6 nm for the nanoparticles with copaiba oil alone. Nanoparticle tracking analysis demonstrated that both suspensions had monomodal profiles and consequently, the nanoparticle populations were homogeneous. This analysis also corroborated the results of dynamic light scattering and laser diffraction, exhibiting a smaller mean diameter for the nanoparticles with copaiba oil and allantoin (143 nm) than for the nanoparticles with copaiba oil (204 nm). The physicochemical properties indicated that the dispersions were stable overtime. Rheology evidenced Newtonian behaviour for both suspensions. Antifungal susceptibility showed a MIC90 of 125 μg/mL (nanoparticles with copaiba oil) and 7.8 μg/mL (nanoparticles with copaiba oil and allantoin) against C. parapsilosis. The nanoparticles with copaiba oil and the nanoparticles with copaiba oil and allantoin presented a MIC90 of 500 μg/mL and 250 μg/mL, respectively, against C. krusei. The MIC90 values were 500 μg/mL (nanoparticles with copaiba oil) and 1.95 μg/mL (nanoparticles with copaiba oil and allantoin) against T. rubrum. Against M. canis, the nanoparticles with copaiba oil and allantoin had a MIC9 of 1.95 μg/mL. In conclusion, nanoencapsulation improved the antifungal activity of copaiba oil, which was enhanced by the presence of allantoin. The MICs obtained are comparable to those of commercial products and can represent promising therapeutics for cutaneous infections caused by yeasts and dermatophytes.
authors.forename: G
authors.initials: G
authors.lastname: Svetlichny
authors.forename: I C
authors.initials: IC
authors.lastname: Külkamp-Guerreiro
authors.forename: S L
authors.initials: SL
authors.lastname: Cunha
authors.forename: F E K
authors.initials: FE
authors.lastname: Silva
authors.forename: K
authors.initials: K
authors.lastname: Bueno
authors.forename: A R
authors.initials: AR
authors.lastname: Pohlmann
authors.forename: A M
authors.initials: AM
authors.lastname: Fuentefria
authors.forename: S S
authors.initials: SS
authors.lastname: Guterres
mesh_terms: D000481:Allantoin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding / Q000379:methods*; D007887:Fabaceae / Q000737:chemistry*; D005658:Fungi / Q000187:drug effects; D008055:Lipids / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010938:Plant Oils / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D012212:Rheology
chemical_list: D000935:Antifungal Agents; D008055:Lipids; D010938:Plant Oils; D000481:Allantoin