Cinnamaldehyde Loaded Poly(lactide-co-glycolide) (PLGA) Microrparticles for Antifungal Delivery Application against Resistant _Candida albicans_ and _Candida glabrata_  
[PERSON]  
1 Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatoratie, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy; [EMAIL_ADDRESS] (S.R. ); [EMAIL_ADDRESS] (M.D.V. ); [PERSON](E.M.); [EMAIL_ADDRESS] (I.F. ); [PERSON]] (M.C. ); [PERSON]A. ); [PERSON].N. ); [EMAIL_ADDRESS] (H.B. ); and [PERSON]  
1 Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatoratie, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy; [EMAIL_ADDRESS] (S.R. ); [PERSON]ESS] (M.D.V. ); [PERSON](E.M.); [EMAIL_ADDRESS] (I.F. ); [EMAIL_ADDRESS] (H.C.); [EMAIL_ADDRESS] (H.A. ); [PERSON].N. ); [EMAIL_ADDRESS] (H.B. ); and [PERSON]  
1 Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatoratie, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy; [EMAIL_ADDRESS] (S.R. ); [PERSON]ESS] (M.D.V. ); [EMAIL_ADDRESS] (E.M.); ilaria. C. albicans_ is an extremely plastic species, able to adapt to host conditions and to be harmless in healthy people and pathogenetic in clinically compromised patients [7]. Although C. albicans is the main cause of human candidiasis, however, the number of infections caused by Non-C. albicans Candida (NCAC) species has significantly increased over the last years [8; 9]. C. glabrata, C. paralysisosis and C. tropicalis are the most common candidiasis cause species, after C. albicans. C. glabrata is a non-polymorphic saprophytic fungus, generally non pathogenetic, present in the intestinal eubiotic microbiota of healthy people. However, the increased use of immunosuppressive and antimicrobial therapies caused an increase of mucosal and systemic C. glabrata infection [10]. Currently, four class of traditional antifungal drugs are used by clinicians and veterinaries for systemic treatment of fungal infections. Antifungal classes are polyenes, azoles, echinocandins and flucytosine. In recent decades, the frequent and prophylactic use of antifungal drugs has led to the development of strong resistance in many Candida species. This represents a significant clinic threat that can cause new epidemics and millions of deaths, so, in recent years, a lot of natural origin molecules are studied as potential antimicrobial agents. Plant extracts, essential oils and their derivates are active against a wide variety of microorganisms [11]. Considerable interest is given to the study of cinnamaldehyde (CIN), one of the main active components of cinnamon essential oil. It is in Cinnamoun genus trees bark, _zeylanicum_, (or _verum_), _canfora_ and _cassia_ species [12]. It has been shown that CIN effectively inhibits bacteria, fungus and mildew growth and their production of toxins [13]. Experimental evidence suggests that CIN shows antifungal activity by inhibiting cell wall biosynthesis, cellular membrane function and to specific enzyme [14]. CIN is a safe natural well-tolerated molecule by human and animals, approved by the Food and Drug Administration (FDA) and the European Council with daily administration within 1.25 mg/kg depend on body weight. Antifungal drugs administration in free form has several disadvantages such as reduced selectivity for pathogenic microorganisms and the risk of compound degradation before reaching the target site [15]. Moreover, because of the acquired resistance by many microorganisms, the administration of a high dose medication is required to have a therapeutic effect. This leads to a higher risk for systemic toxicity and side effects such as allergic reaction, hepatotoxicity, nephrotoxicity and damage to the healthy microbiota [16]. The use of drug delivery systems can overcome these disadvantages. Finally, drug delivery systems are advantageous for active compounds with low solubility and stability.