Table 5.

Examples of brinzolamide-loaded nanoparticulate systems

Hypotensive drug/nanosystem	Pharmaceutical form	Study design/model	Results	References
Brinzolamide (BZL)-loaded liquid crystalline nanoparticles (BZL LCNPs)	Liquid crystalline nanoparticles	In vitro release study to measure the release of BZL from LCNPs Ex vivo corneal penetration study (employing New Zealand rabbits) Efficacy study (instillation of one drop of marketed BZL, 1% BZL solution, and BZL LCNPs)	Ex vivo permeability coefficient of BZL LCNPs showed a 3.47-fold increase compared with commercial BZL Two hours after instillation, peak IOP decrease was 47.67 ± 3.58% by BZL LCNPs, and 33.75 ± 4.35% by commercial BZL	[145]
BZL nanocrystal suspensions (BZL-Npsa)	Nanocrystal	Cellular toxicity assay using human corneal epithelial cells (standard cell viability method)	BZL-Npsa pH 4.5 lowered IOP after 60 min (71.4 ± 5.0%) more efficiently than BZL-Npsa pH 7.4 Polysorbate 80 formulation (51.0 ± 26.3%), and commercial BZL (49.6 ± 16.5%)	[146]
		In vivo studies: to verify IOP reduction following BZL-Npsa in glaucomatous Wistar rats	All the tested formulations and commercial BZL showed mild or no toxicity to the human corneal epithelial cells
Trimethyl lock (TMLo) BZL prodrug nanoparticles	Nanocrystals	Instillation of nano eye drops of BZL prodrug in ocular normotensive Sprague–Dawley rats	TMLo BZL prodrug nano eye drops showed similar efficacy as commercial BZL at 1/5 the molar concentration (5.67 mM TMLo BZL prodrug nano eye drops were as effective as 26.1 mM Azopt™), with no toxic effects to the cornea	[147]
BZL nanoemulsions (BZL NEs)   Seven primary BZL NE combinations were used [variations of four nonionic surfactants (Tyloxapol, Labrasol, Cremophor (RH40), and Brij 35), two oils (Capryol 90 and triacetin), and one co-surfactant (Transcutol P)]   The amount of BZL was 0.4% in all formulations	Nanoemulsions	In vitro drug release studies In vivo therapeutic studies (ocular normotensive New Zealand albino rabbits): BZL NEs were instilled, followed by IOP measurements at 30, 60, 120, 180, 240, 300, and 360 min after instillation	BZL NEs displayed a sustained release profile with proper physicochemical characteristics, facilitating BZL penetration into the corneal tissue with lower drug concentrations (0.4% vs 1% with commercial BZL)	[148]
BZL-hydroxypropyl-cyclodextrin (BZL-HP-β-CD) inclusion complex	Cyclodextrins	In vitro corneal permeability and release studies In vivo study (New Zealand normotensive rabbits): Group A: BZL-HP-β-CD 0.2% inclusion complex; Group B: BZL-HP-β-CD 0.5% inclusion complex; Group C: commercial BZL (1%) IOP measured 30, 60, 120, 150, 180, 240, and 300 min after instillation	In vitro corneal accumulation and permeability of the BZL-HP-β-CD inclusion complex was increased 2.91-fold compared to commercial BZL Solubility of BZL increased 10-fold with the (BZL-HP-β-CD) inclusion complex (BZL-HP-β-CD) inclusion complex (0.5% BZL) showed IOP-lowering efficacy comparable to commercial BZL in vivo	[56]
Brinzolamide (BZL)-hydropropyl-β-cyclodextrin (HP-β-CD) inclusion complex (HP-β-CD/BZL) into nanoliposomes “HP-β-CD/BZL-loaded nanoliposomes” (BCL)	Liposomes Cyclodextrins	In vitro BZL release study Transcorneal permeability study In vivo IOP measurement	BZL showed a moderate sustained release period of 9 h (1–10 h) BCL showed a 9.36-fold increase in the permeability coefficient compared with commercially available BZL BCL formulation reduced IOP in less than 1 h, reached peak efficacy (− 32.3%) at 2 h and showed a sustained effect for 12 h BZL suspension lowered IOP at 30 min and reached its peak efficacy at 1 h. From 2 to 12 h after instillation, BCL resulted in significantly lower IOPs compared with BZL suspension	[149]
Brinzolamide (BZL)-loaded PLGA nanoparticles	Poly(lactic-co-glycolic acid) (PLGA) nanoparticles	A single subconjunctival injection of BZL-PLGA nanoparticles In vitro drug release studies In vivo IOP measurements (on normotensive albino rabbits)	Two formulations of BZL-loaded PLGA nanoparticles displayed excellent release efficiency values: A19 released about 70% of the drug in 6 months, while B11 released about 90% of the drug in 6 months After subconjunctival administration peak IOP lowering were 78.4 ± 3.4% for A19 BZL nanoparticles; 71.6 ± 2.0% for B11 BZL nanoparticles; and 56.8 ± 6.3% for BZL aqueous suspension	[150]