Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec;28(1):2177-2186.
doi: 10.1080/10717544.2021.1989090.

Novel cubosome based system for ocular delivery of acetazolamide

Hoda E Teba  1 , Islam A Khalil  1 , Heba M El Sorogy  1
Affiliations

Novel cubosome based system for ocular delivery of acetazolamide

Hoda E Teba et al. Drug Deliv. 2021 Dec.

Abstract

Acetazolamide is the drug of choice for glaucoma treatment in an emergency. However, it is not available in any topical formulation and it is available only as systemic tablets. Despite its efficiency as a drug in decreasing intraocular pressure, it has negative systemic effects as renal toxicity and metabolic acidosis. Moreover, it suffers from poor aqueous solubility and low corneal permeability limiting its ocular bioavailability and its use topically. Cubosomes have enormous advantages as a drug delivery system, most importantly, high surface area, thermal stability, and ability to encapsulate hydrophobic, amhiphilic, and hydrophilic molecules. Herein, we have exploited the unique properties of cubosomes as a novel nano-delivery system for acetazolamide as eye drops dosage form for glaucoma treatment. Different acetazolamide-loaded cubosomes have been developed and evaluated. The best-optimized formulation (F5), was cubic shaped structure, with an average particle size of 359.5 ± 2.8 nm, surface charge -10.8 ± 3.2 mV, and 59.8% entrapment efficiency. Ex-vivo corneal permeation studies have revealed a 4-fold increase in acetazolamide permeability coefficient compared to that stated in the literature. F5 showed superior therapeutic efficacy represented by a 38.22% maximum decrease in intraocular pressure vs. 31.14 and 21.99% decrease for the commercial Azopt® eye drops and Cidamex® tablets, respectively. It also exhibited higher (AUC0-10) compared to Azopt® eye drops and Cidamex® tablets by 2.3 and 3 times, respectively. F5 showed mean residence time 4.22 h vs. 2.36 and 2.62 h for Azopt® and Cidamex® with no eye irritation observed according to the modified Draize test. To the best of our knowledge, this is the first study for developing acetazolamide-loaded cubosomes as the topical delivery system for glaucoma treatment.

Keywords: Glaucoma; acetazolamide; carbonic anhydrase inhibitor; cubosomes; intraocular pressure; ocular drug delivery.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Effect of formulation variables on particle size and E.E% (mean ± SD) of cubosomes (n = 3). (a) effect of GMO : water ratio, (b) effect of GMO: P 407 ratio, (c) effect of type and concentration of aqueous stabilizer.
Figure 2.
Figure 2.
ACZ permeation from different ACZ-loaded cubosomes through the excised goat cornea (mean ± SD, n = 3).
Figure 3.
Figure 3.
Particle size distribution of F5 cubosomes dispersion.
Figure 4.
Figure 4.
Transmission electron microscopy images of ACZ-loaded cubosomes.
Figure 5.
Figure 5.
Percentage decrease in IOP after topical application of F5, Azopt eye drops, and oral administration of Cidamex tablets (mean ± SD, n = 3).
See this image and copyright information in PMC

References

    1. Allison K, Patel D, Alabi OJC. (2020). Epidemiology of glaucoma: the past, present, and predictions for the future. Cureus 12:1–9. - PMC - PubMed
    1. Ammar HO, Salama H, Ghorab M, Mahmoud A. (2009). Nanoemulsion as a potential ophthalmic delivery system for dorzolamide hydrochloride. AAPS PharmSciTech 10:808–19. - PMC - PubMed
    1. Baeyens V, Felt-Baeyens O, Rougier S, et al. (2002). Clinical evaluation of bioadhesive ophthalmic drug inserts (BODI®) for the treatment of external ocular infections in dogs. J Controlled Release 85:163–8. - PubMed
    1. Barar J, Javadzadeh AR, Omidi Y. (2008). Ocular novel drug delivery: impacts of membranes and barriers. Expert Opin Drug Deliv 5:567–81. - PubMed
    1. Bravo-Osuna I, Vicario-De-La-Torre M, Andrés-Guerrero V, et al. (2016). Novel water-soluble mucoadhesive carbosilane dendrimers for ocular administration. Mol Pharm 13:2966–76. - PubMed

MeSH terms

LinkOut - more resources