Nanostructured Lipid Carriers for Ocular Acetazolamide Delivery

PALMIERI, PABLO TOMÁS ; AWDE ALFONSO, HAMOUDI GHASSAN; PALMA, SANTIAGO DANIEL; FORMICA, MARÍA LINA

Rosario

Congreso; 7MA REUNIÓN INTERNACIONAL DE CIENCIAS FARMACÉUTICAS; 2023

Glaucoma is characterized by increased intraocular pressure (IOP) which results in blindness if left untreated. Acetazolamide (ACZ) inhibits carbonic anhydrase activity in the ciliary processes of the eye and, consequently, reduces aqueous humor production and IOP. However, ACZ presents poor ocular bioavailability after its eye topical application, thereby high-dose oral administration of ACZ is required to provide a therapeutic concentration in the eye due to the low solubility and a very short half-life, which lead to systemic side effects such as renal failure or metabolic acidosis. In this way, the aim of this study is the development of novel acetazolamide-loaded nanostructured lipid carriers (ACZ-NLC) as an optimization strategy for the ocular application of ACZ.The incorporation of ACZ in the aqueous or lipid phase was studied in the preparation of nanostructured lipid carriers (NLC) composed of 5,5% total lipids and 5% surfactants by ultrasonication method. ACZ-NLC were characterized by dynamic light scattering (DLS) to determine the average particle size, polydispersity index (PDI) and zeta potential. Then, the ultracentrifugation method with Amicon® Ultra centrifugal filters (MWCO 100 kDa) was used to separate the free drug and encapsulated drug, following the drug quantification by UV spectroscopy analysis. The percentage of encapsulation efficiency (EE%) was calculated. ACZ-NLC prepared by drug dispersion in the lipid phase showed an average particle size of (157±3) nm, PDI of (0.26 ± 0.06) and a zeta potential of (-66 ± 9) mV. Furthermore, these lipid nanoparticles demonstrated an encapsulation efficiency of (86.3 ± 0.1)%. These preliminary studies showed that NLC allow the encapsulation of ACZ and could be a potential drug delivery system for ACZ. Further efforts will be carried out to characterize and evaluate the in vivo ocular application of ACZ-NLC.