Acetazolamide encapsulation in elastin like recombinamers using a supercritical antisolvent (SAS) process for glaucoma treatment

• Published in: International journal of pharmaceutics 2024-05, Vol.657, p.124098-124098, Article 124098
• Main Authors: Vallejo, Reinaldo, Quinteros, Daniela, Gutiérrez, Javier, Martínez, Sofía, Rodríguez Rojo, Soraya, Ignacio Tártara, Luis, Palma, Santiago, Javier Arias, Francisco
• Format: Article
• Language: English
• Subjects: Acetazolamide; Acetazolamide - administration & dosage; Acetazolamide - chemistry; Acetazolamide - pharmacokinetics; Animals; Biological Availability; Carbonic Anhydrase Inhibitors - administration & dosage; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacokinetics; Cornea - drug effects; Cornea - metabolism; Delayed-Action Preparations - chemistry; Drug Compounding - methods; Elastin - chemistry; Elastin-like recombinamers; Glaucoma - drug therapy; Intraocular Pressure - drug effects; Male; Nanoparticles; Nanoparticles - chemistry; Ophthalmic drug delivery; Permeability; Rabbits; Solubility; Solvents - chemistry; Supercritical Antisolvent
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124098

[Display omitted] •Encapsulation of acetazolamide in ELRs nanoparticles using SAS technique.•ELR-based nanoparticles system offering more permeation ocular of Acetazolamide.•Tests on hypertensive rabbits show high bioavailability and hypotensive effect. Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of –33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance.