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

Area of Science:

• Biomaterials Science
• Ophthalmology
• Drug Delivery Systems

Background:

• Glaucoma is a leading cause of blindness globally, necessitating advanced therapeutic strategies.
• Current treatments face challenges due to drug solubility and permeability issues.
• Novel drug delivery systems are crucial for enhancing therapeutic efficacy.

Purpose of the Study:

• To develop and characterize a novel controlled-release system for acetazolamide (AZM) in glaucoma treatment.
• To encapsulate AZM within elastin-like recombinamers (ELR) using the Supercritical Antisolvent (SAS) technique.
• To evaluate the physicochemical properties, ocular permeation, safety, and in vivo efficacy of the developed nanoparticles.

Main Methods:

• Encapsulation of acetazolamide (AZM) into amphiphilic elastin-like recombinamers (ELR) via the Supercritical Antisolvent (SAS) technique.
• Characterization of micro/nanoparticles using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Atomic Force Microscopy (AFM).
• Assessment of nanoparticle stability (zeta potential), transcorneal permeation, ocular irritation, and intraocular pressure (IOP) reduction in hypertensive rabbits.

Main Results:

• Successful encapsulation of AZM in ELR with yields up to 62%, forming spherical microparticles that disintegrate into ~42 nm nanoparticles.
• Stable, non-aggregating nanoparticles with a zeta potential of -33 mV over 30 days.
• Enhanced transcorneal permeation (up to 30% increase) and significant IOP reduction in rabbits with no observed ocular irritation.

Conclusions:

• The ELR-based nanoparticles produced via SAS technique offer a promising, safe, and effective drug delivery system for glaucoma.
• This approach enhances acetazolamide bioavailability and therapeutic outcomes, potentially improving clinical management of glaucoma.
• The combination of recombinant biopolymers and high-pressure techniques holds significant potential for advancing glaucoma therapy.