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

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. Acetaz...

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Detalles Bibliográficos
Autores: Vallejo, Reinaldo, Quinteros, Daniela, Gutiérrez, Javier, Martínez, Sofía, Rodriguez-Rojo, Soraya, Tártara, Luis Ignacio, Palma, Santiago, Arias, Francisco Javier
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::fae9cb06d553c03cba6379632abc02ff
Acceso en línea:http://hdl.handle.net/10261/368416
Access Level:acceso abierto
Palabra clave:Acetazolamide
Elastin-like recombinamers
Nanoparticles
Supercritical Antisolvent
Ophthalmic drug delivery
Descripción
Sumario: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.