Amoebicidal Potential\nof β‑Caryophyllene-Loaded\nPolymeric Nanoparticles

The\ninvestigation of therapeutic agents for <i>Acanthamoeba</i> keratitis (AK) is necessary as nonspecific, toxic, and long-lasting\ntreatments are currently found. In this study, ß-caryophyllene\nwas selected as an anti-<i>Acanthamoeba</i> candidate due\nto its known anti-inflammatory and analgesic activities, which are\npharmacological actions desirable for this application. On the other\nhand, this sesquiterpene presents a low aqueous solubility, high volatility,\nand susceptibility to oxidation, which motivated its incorporation\ninto polymeric nanoparticles (NPs). Chitosan (CS) was selected as\nthe biopolymer due to its bioadhesive properties and wide use in ophthalmic\npreparations, which was cross-linked with tripolyphosphate (TPP) to\nobtain stable particles. Monodisperse NPs with reduced size (<245\nnm) and presenting a positive surface charge (ζ-potential between\n+15.23 and +18.15 mV) were obtained regardless of the type of chitosan\nselected. The colloidal suspensions were stable for up to 60 and 90\ndays after storage at 25 and 4 °C, respectively. The nanoencapsulation\nof ß-caryophyllene led to a series of benefits: (a) increased\nits activity against Acanthamoeba castellanii trophozoites; (b) reduced corneal toxicity as no more collagen disruption\nwas found in the stroma; and (c) increased retention and mucoadhesion\nin corneal tissue. In view of these positive results, <i>in vivo</i> studies are encouraged, as well as formulation studies including\npotential therapeutic agents in this same nanocarrier.