Potential antibiofilm activity of farnesol-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles against Candida albicans

Abstract

Candida species are ubiquitous fungal pathogens and are the most common causes of mucosal and invasive fungal infections in humans. Especially Candida albicans commonly resides as a commensal in the mucosal tissues of approximately half of the human population. When the balance of the normal flora is disrupted or the immune defenses are compromised, Candida species can become pathogenic, often causing recurrent disease in susceptible individuals. The treatments available for Candida infection are commonly drug-based and can involve topical and systemic antifungal agents. However, the use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. Candida species ability to produce drug-resistant biofilm is an important factor in human infections, because microorganisms within biofilm benefit from various advantages over their planktonic counterparts including protection from antimicrobials and chemicals. These limitations emphasize the need to develop new and more effective antifungal agents. Natural products are attractive alternatives for this purpose due to their broad spectrum of biological activities. Farnesol is produced by many microorganisms and found in some essential oils. It has also a great attention as a quorum-sensing molecule and virulence factor. It has also antimicrobial potential due to its inhibitory effects on various bacteria and fungi. However, as it is a hydrophobic component, its solubility and biofilm inhibiting properties are limited. To overcome these shortcomings, nanoparticle-based drug delivery systems have been successfully used. For this purpose, especially using biodegradable polymeric nanoparticles has gained increasing attention owing to their biocompatibility and minimal toxicity. Poly (DL-lactide-co-glycolide) (PLGA) is the most widely used polymer in this area. In this study, farnesol is loaded to PLGA nanoparticles (F-PLGA NPs) by emulsion evaporation method and characterized by DLS, TEM, and FT-IR analyses. Our TEM findings indicate that the sizes of F-PLGA NPs are approximately 140 nm. The effects of F-PLGA NPs on planktonic cells and biofilm formation of C. albicans were compared with effects of farnesol alone. Farnesol inhibits the growth at a range of 53% at a concentration of 2.5 μL compared to the control group. This rate is 45% for F-PLGA NPs at the same concentration. However, although farnesol amount in F-PLGA is approximately 22.5% of the total volume, the observed effect is significant. In TEM examinations, planktonic Candida cells treated with farnesol showed relatively regular ultrastructural morphology. Few membrane and wall damage and electron density in the cytoplasm were determined. In F-PLGA NP-treated cells, increased irregular cell morphology, membrane and wall damages, and large vacuoles are observed. Our SEM and XTT data suggest that F-PLGA NPs can reduce the biofilm formation at lower concentrations than farnesol alone 57%, and our results showed that F-PLGA NPs are effective and biocompatible alternatives for inhibiting growth and biofilm formation of C. albicans, but detailed studies are needed.

Antibiofilm Synergistic Activity of Streptomycin in Combination with Thymol-Loaded Poly (Lactic-co-glycolic Acid) Nanoparticles against Klebsiella pneumoniae Isolates

“…The nanoparticle size substantially impacts the diffusion of Thy-NPs into the biofilm matrix, leading to more damage to the biofilm cells. The nanoparticle's surface charge can be responsible for specific biofilm targeting by electrostatic interactions with the biofilm matrix, favoring the attachment of nanoparticles to the biofilm matrix and resulting in the release of the drug inside the biofilm [ 15 , 30 ]. Additionally, the nanoparticle's high surface-area-to-volume ratio could enable high penetration of the drug, which may result in stronger antibiofilm efficacy [ 31 ].…”

Green fabrication of chitosan nanoparticles using Lavendula angustifolia, optimization, characterization and in‑vitro antibiofilm activity

“…Accordingly, the antibiofilm activity of CNPs at different concentrations was investigated, in response to P. aeruginosa , S. aureus and C. albicans as representative strains of gram-negative, gram-positive bacteria and eukaryotic biofilm-forming pathogens, respectively. Their pathogenicity was listed tremendously in food intoxication, water-borne diseases and nosocomial infections 96 , 97 . Herein, crystal violet was employed to detect the biofilm inhibition directly on the bottom and inner walls of the microtiter plate.…”

Addressing Antimicrobial Properties in Guided Tissue/Bone Regeneration Membrane: Enhancing Effectiveness in Periodontitis Treatment

“…Their results showed that F-PLGA nanoparticles are effective and biocompatible alternatives to inhibit the growth and biofilm formation of C. albicans. 140 In another study, PLGA nanoparticles were studied for antibiotic delivery in periodontitis. Kashi et al developed a new method for producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections.…”

“…Gorso et al used emulsion evaporation method to load farnesol into PLGA nanoparticles (F-PLGA NPs). Their results showed that F-PLGA nanoparticles are effective and biocompatible alternatives to inhibit the growth and biofilm formation of C. albicans . In another study, PLGA nanoparticles were studied for antibiotic delivery in periodontitis.…”