Send Orders for Reprints to reprints@benthamscience.net Current Nanomedicine, XXXX, XX, 1-15 1 2468-1873/XX $65.00+.00 © XXXX Bentham Science Publishers MINI-REVIEW ARTICLE Nanocarrier-based Drug Delivery of Brinzolamide for Ocular Diseases: A Mini-Review Rashmi Maurya 1 , Akash Vikal 1 , Preeti Patel 2 , Raj Kumar Narang 3 and Balak Das Kurmi 1,* 1 Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India; 2 Department of Pharmaceutical Chemistry, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India; 3 ISF College of Phar- macy and Research, Indo Soviet Friendship College of Pharmacy Rattian Road, Moga-142048, Punjab, India ARTICLE HISTORY Received: November 22, 2023 Revised: February 23, 2024 Accepted: April 04, 2024 DOI: 10.2174/0124681873294344240408061056 Abstract: Brinzolamide (BRZ) represents a significant advancement in glaucoma treatment as a topically active carbonic anhydrase inhibitor (CAI). It exhibits selectivity and potent inhibitory ac- tivity for carbonic anhydrase type II isozyme (CA-II), which is crucial in aqueous humor secre- tion. With excellent ocular bioavailability and a formulation optimized for physiologic pH, brinzo- lamide effectively lowers intraocular pressure by inhibiting CA-II in ciliary processes. Its superior ocular comfort profile enhances patient compliance. Preclinical evaluations confirm its specific CA inhibition without notable side effects, and its low systemic absorption minimizes systemic CA inhibition-related issues. BRZ's prolonged tissue half-life in the eye ensures sustained IOP re- duction, supported by clinical trials demonstrating comparable efficacy with reduced dosing fre- quency. Challenges in ocular disease treatment arise from physiological, anatomical, and dynamic barriers hindering effective drug delivery to the eye. Nanocarriers, such as micelles, nanoparticles, liposomes, niosomes, and dendrimers, offer promising solutions by improving permeation, target- ing specific sites, and overcoming the limitations of conventional forms. This review explores di- verse nanomedicines, detailing their applications, advantages, and disadvantages in ophthalmic drug delivery. It also includes recent research findings for a comprehensive overview of the cur- rent landscape. Keywords: Brinzolamide, nanocarriers, intraocular pressure, carbonic anhydrase inhibitors. 1. INTRODUCTION Intraocular pressure (IOP) and open-angle glaucoma (OAG) are treated with a novel topically active carbonate an- hydrase inhibitor, brinzolamide (BRZ), a second-generation therapeutic medication. The use of BRZ is severely cons- trained by its solubility. However, it can be avoided by en- capsulating BRZ in nanoparticles (NPs) [1, 2]. BRZ is the newest topical CAI to be successfully developed and market- ed. BRZ, also recognized as AL-4862, refers to the R-(1) enantiomer of a compound named 4-ethylamino-3,4-dihy- dro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6- sulfonamide, 1,1-dioxide. The empirical formula of BRZ is C 12 H 21 N 3 O 5 S 3 . This compound belongs to the thienothiazine sulfonamide group and possesses an unbound amine. Its molecular weight is 383.51g/mol (Table 1) [3]. Physically, it is a white powder that is insoluble in water [4]. It is an aque- ous suspension formulated as 1% ophthalmic suspension to reduce IOP with a recommended dosing frequency of three times daily in the US and twice daily in the EU and Japan [4]. Particularly in areas where carbonic anhydrase II (CA-I- I) is concentrated, BRZ exhibits a notable affinity for bind- ing to red blood cells. The systemic carbonic anhydrase * Address correspondence to this author at the Department of Pharmaceu- tics, ISF College of Pharmacy, GT Road, Moga-142001, Punjab, India; Tel: +91-9754275553; E-mail: bdkurmi@gmail.com (CA) inhibition brought on by BRZ has no negative effects as long as there is still enough CA-II activity. N-Diethyl BRZ, one of its metabolites, is also produced during the pro- cess [5]. BRZ and dorzolamide exhibit the highest potency against CA-II, displaying reduced activity against CA-IV and, subsequently, CA-I. The IC50 values for acetazo- lamide, dorzolamide, and BRZ against CA-IV are compara- ble and generally an order of magnitude lower than those for CA-II. The clinical implications of this in relation to effec- tiveness in lowering intraocular pressure and potential side effects remain unknown. BRZ has a higher lipophilicity to facilitate diffusion across the blood-retinal barrier (BRB) [6]. It was approved by the FDA in 1998 as a standalone product and in 2013 as a combination product with brimoni- dine tartrate in Europe. It was also approved as a combina- tion product with timolol in 2008 [7]. The commercial prod- uct of BRZ is called Azopt ® (US brand), Azopt 1 (Canadian brand), Brinzox, Brinzox T, Brinolar, Brinzagan, Brinzoma, Lupibrin, Bridic, Brinzemic, and Brinzodoc, composed of 1% (w/v) BRZ [8]. CA, the enzymes that catalyze the rev- ersible reaction of H 2 O and CO 2 to generate bicarbonate ions, are highly specific, reversible, and non-competitive en- zyme inhibitors [9]. Despite the fact that human tissues con- tain seven different isoforms of CA, BRZ has the strongest affinity for CA II [3, 9]. The high level of safety of BRZ is explained by the fact that neither BRZ nor any of its active Author Proofs “For Personal Use Only”