Advances in dorzolamide hydrochloride delivery: harnessing nanotechnology for enhanced ocular drug delivery in glaucoma management

Abstract

Dorzolamide hydrochloride (DRZ) is a carbonic anhydrase inhibitor utilized in managing elevated intraocular pressure (IOP) associated with glaucoma. However, its clinical effectiveness is hindered by a short half-life, low residence time, and the need for frequent dosing, highlighting the necessity for innovative delivery systems. This work reviews recent advancements in DRZ delivery, particularly focusing on cyclodextrin complexation and nanotechnology applications. It explores the potential of cyclodextrin derivatives to enhance DRZ's bioavailability. DRZ cyclodextrin complexes or nanoparticulate systems maintain high drug concentrations in the eye while minimizing irritation and viscosity-related issues. Nanotechnology introduces nanoparticle-based carriers such as polymeric nanoparticles, solid lipid nanoparticles, liposomes, niosomes, and nanoemulsions. These formulations enable sustained drug release, improved corneal permeation, and enhanced patient compliance. Clinical trials have shown that DRZ nanoparticle eye drops and nanoliposome formulations offer efficacy comparable to conventional therapies, with the potential for better tolerability. Overall, this review highlights significant progress in DRZ delivery systems, suggesting their potential to transform glaucoma treatment by addressing current limitations and improving therapeutic outcomes.

Keywords: Cyclodextrin complexation; Dorzolamide hydrochloride; Drug delivery; Glaucoma; Nanotechnology.

Fig. 1

Glaucoma disease statistics involving number of review papers published, clinical trials conducted, meta analysis completed and genderwise patients distribution from year 2000 to 2024. The types of studies considered include randomized clinical trials, cohort studies, case–control studies, types of medical or procedural interventions, glaucoma progression, treatment efficacy, side effects, and patient demographics. (Created by using Pubmed database)

Fig. 2

A summary of ocular drug delivery systems, including ocular diseases, conventional treatments, and advanced approaches for enhanced therapeutic outcomes. (Created by using Biorender.com)

Fig. 3

Mechanisms of glaucoma involving 1. Flow of aqueous humor and drainage canal 2. Blocked drainage canal 3. Increased intraocular pressure induced damages into blood vessels along with optic nerve 4. Involvment of reactive glial cells, reactive muller cells and reactive astrocytes in optic nerve damages. (Created by using Biorender.com)

Fig. 4

This figure illustrates the role of carbonic anhydrase in lacrimal fluid production and the role of dorzolamide in inhibiting carbonic anhydrase II, leading to decreased intraocular pressure. Carbonic anhydrase is essential for the production of lacrimal fluid. Parasympathetic agonists increase intracellular calcium ions, which in turn stimulate the sodium-hydrogen exchanger by activating the chloride-bicarbonate exchanger. The basolateral membrane is involved in this process, driving sodium and chloride ions into the duct cells. Intracellular carbonic anhydrase is required for the generation of hydrogen and bicarbonate ions, which facilitate the movement of sodium and chloride ions. The increase in intracellular potassium and chloride ions drives these ions out of the cell into the lumen through potassium and chloride channels, as well as potassium-chloride co-transporters. Oral carbonic anhydrase inhibitors are used in glaucoma cases with elevated IOP to reduce intraocular pressure by inhibiting sodium ion, bicarbonate ion, and aqueous humor production, although they present challenges related to targeted delivery and solubility. Dorzolamide has demonstrated better specificity for carbonic anhydrase II, effectively reducing intraocular pressure [11]. (Created using Biorender.com)

Fig. 5

Chemistry and SAR of dorzolamide for CA inhibitory and ocular activity. (Created by using Biorender.com)

Fig. 6

It represented 1. Challenges in conventional glaucoma therapy 2. Need of nanotechnology in glaucoma 3. Types of nanocarriers used in glaucoma. (Created by using Biorender.com)

Fig. 7

Dorzolamide concentration (mcg/mL) in aqueous humour after topical administration to rabbits (mean ± standard deviation; n = 6–8): formulation 3A (O) (3% dorzolamide ⁄ γCD eye drop microsuspension) and Trusopt^® $(\bullet )$. (Reproduced from Loftsson et al. [1] with kind permision of copyright holder, Wiley)

Fig. 8

Graph illustrating the drug release study of the dorzolamide (DRZ) solution and optimized DRZ-SLNs. Reproduced from Shahab et al. [57] with the kind permission of the copyright holder, Elsevier

Fig. 9

Effect of Lipid Composition on the Release Profile of Dorzolamide (Dorzo). Niosomes with Span 20 (DN1) exhibited a faster release, while those with Span 40 (DN2) and Span 60 (DN3) showed slower release due to higher phase transition temperatures (Tc). Span 85 (DN4) had a release rate similar to that of DN1. The addition of DCP (DN5) further reduced the release rate. Mixed niosomes containing Span 40 and Tween (DN6, DN7, DN8) delayed release, with the greatest reduction observed in DN7 (Tween 40) and the least in DN8 (Tween 80), likely due to differences in membrane rigidity and alkyl chain properties. The data represent the mean ± SD of six determinations. Reproduced from Hasan et al. [80] with the kind permission of the copyright holder, Taylor & Francis