دارورسانی دوتایی در نانوذرات لیپید جامد برای درمان بیماری قارچی
Abstract
1- Introduction
2- Materials and methods
3- Results and discussion
4- Conclusions
References
Abstract
Nowadays, a combinatorial drug delivery system that simultaneously transports two or more drugs to the targeted site in a human body, also recognized as a dual-drugs delivery system, represents a promising strategy to overcome drug resistance. Solid lipid nanoparticles loaded with clotrimazole (CLZ) and alphalipolic acid (ALA), considered as an effective agent in the reduction of reactive oxygen species, can enhance anti-infective immunity being proposed as a non-toxic and mainly non-allergic dual-drugs delivery system. In this study, uncoated and cationic CLZ-ALA-loaded SLN were prepared and compared. Suspensions with a narrow size distribution of particles of mean size below 150 nm were obtained, having slight negative or highly positive zeta potential values, due to the presence of the cationic lipid, which also increased nanoparticles stability, as confirmed by Turbiscan® results. Calorimetric studies confirmed the rationale of separately delivering the two drugs in a dual-delivery system. Furthermore, they confirmed the formation of SLN, without significant variation in presence of the cationic lipid. In vitro release studies showed a prolonged drug release without the occurrence of any burst effect. In vitro studies performed on 25 strains of Candida albicans showed the antimicrobial drug activity was not altered when it was loaded into lipid nanoparticles. The study has proved the successfully encapsulation of CLZ and ALA in solid lipid nanoparticles that may represent a promising strategy to combine ALA protective effect in the treatment with CLZ.
Introduction
Fungal infections, most of all candidiasis, represent an increasing challenge affecting global health, that in many cases produces morbidity and mortality in immunocompromised and intensive care unit patients [1,2]. Among different types of fungi, Candida albicans represents the main cause of fungal diseases, responsible of both orally and vaginally yeast infections, overall when a decrease in Lactobacillus concentration appears [3]. Usually, polyenes, echinocandins and azoles are the most used drugs for the treatment of fungal infections [4], even if the requirement of early treatment and the occurrence of side effects still limit the efficiency of the therapy. Among azoles, Clotrimazole (CLZ) is one of the most broad-spectrum antimycotic drug used for the treatment of vulvovaginal and oropharyngeal candidiasis [5]. Moreover, CLZ has been claimed to show a selective antibacterial activity [6,7] and ability to inhibit in vitro Streptococcus mutans biofilm and virulence [8]. CLZ antifungal activity is related to its capability to interfere with the biosynthesis of ergosterol, the major component of the fungal cytoplasmic membrane, with the consequent depletion of ergosterol and its replacement with the aberrant sterol species, 14-amethylsterol, thus disturbing the membrane permeability and fluidity [9]. However, the increasing antifungal resistance to azoles, mainly among immunocompromised patients, strongly limits the effective treatment of mycoses [10]. Combinatorial drug delivery is a promising strategy to prevent potential drug resistance [11]. We have recently demonstrated the possibility to improve CLZ effectiveness exploiting its nanoencapsulation in lipid nanoparticles prepared by additionally using of essential oils from Mediterranean area, highlighting their synergistic effect [12].