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.

中文翻译：

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负载法尼醇的聚（DL-丙交酯-共-乙交酯）（PLGA）纳米颗粒对白色念珠菌的潜在抗生物膜活性

念珠菌属普遍存在的真菌病原体，是人类粘膜和侵袭性真菌感染的最常见原因。尤其是白色念珠菌通常作为共生菌存在于大约一半人口的粘膜组织中。当正常菌群的平衡被破坏或免疫防御受到损害时，念珠菌属会致病，通常会导致易感个体的疾病复发。可用于念珠菌感染的治疗通常是基于药物的，可能涉及局部和全身性抗真菌药物。然而，标准抗真菌疗法的使用可能因毒性、低效率和耐药性而受到限制。念珠菌种产生耐药生物膜的能力是人类感染的重要因素，因为与浮游微生物相比，生物膜中的微生物受益于各种优势，包括免受抗菌剂和化学品的侵害。这些限制强调需要开发新的和更有效的抗真菌剂。由于其广泛的生物活性，天然产品是用于此目的的有吸引力的替代品。Farnesol 由许多微生物产生，并存在于一些精油中。它作为群体感应分子和毒力因子也备受关注。由于其对各种细菌和真菌的抑制作用，它还具有抗菌潜力。然而，由于它是一种疏水组分，其溶解性和生物膜抑制特性是有限的。为了克服这些缺点，已成功使用基于纳米颗粒的药物递送系统。以此目的，特别是使用可生物降解的聚合物纳米粒子由于其生物相容性和最小的毒性而受到越来越多的关注。聚（DL-丙交酯-共-乙交酯）（PLGA）是该领域使用最广泛的聚合物。在这项研究中，法尼醇通过乳液蒸发法加载到 PLGA 纳米粒子 (F-PLGA NPs) 上，并通过 DLS、TEM 和 FT-IR 分析进行表征。我们的 TEM 发现表明 F-PLGA NP 的尺寸约为 140 nm。将 F-PLGA NPs 对浮游细胞和白色念珠菌生物膜形成的影响与单独使用法尼醇的影响进行了比较。与对照组相比，Farnesol 在 2.5 μL 的浓度下抑制了 53% 的生长。对于相同浓度的 F-PLGA NP，该比率为 45%。然而，虽然 F-PLGA 中法尼醇的量约为总体积的 22.5%，观察到的效果是显着的。在 TEM 检查中，用法尼醇处理的浮游念珠菌细胞显示出相对规则的超微结构形态。细胞质中很少有膜和壁损伤以及电子密度。在 F-PLGA NP 处理的细胞中，观察到不规则细胞形态增加、膜和壁损伤以及大液泡。我们的 SEM 和 XTT 数据表明，F-PLGA NPs 可以在低于法尼醇的浓度下减少生物膜形成 57%，我们的结果表明 F-PLGA NPs 是抑制白色念珠菌生长和生物膜形成的有效和生物相容性替代品，但需要详细研究。细胞质中很少有膜和壁损伤以及电子密度。在 F-PLGA NP 处理的细胞中，观察到不规则细胞形态增加、膜和壁损伤以及大液泡。我们的 SEM 和 XTT 数据表明，F-PLGA NPs 可以在低于法尼醇的浓度下减少生物膜形成 57%，我们的结果表明 F-PLGA NPs 是抑制白色念珠菌生长和生物膜形成的有效和生物相容性替代品，但需要详细研究。细胞质中很少有膜和壁损伤以及电子密度。在 F-PLGA NP 处理的细胞中，观察到不规则细胞形态增加、膜和壁损伤以及大液泡。我们的 SEM 和 XTT 数据表明，F-PLGA NPs 可以在低于法尼醇的浓度下减少生物膜形成 57%，我们的结果表明 F-PLGA NPs 是抑制白色念珠菌生长和生物膜形成的有效和生物相容性替代品，但需要详细研究。