Table 6.

Examples of brimonidine-loaded nanoparticulate systems

Hypotensive drug/nanosystem	Pharmaceutical form	Study design/model	Results	References
Nanovesicles of BRD	Liposomes and niosomes	In vitro and ex in vitro drug release studies In vivo IOP-lowering activity in albino rabbits   Group 1: marketed formulation (BRD 0.02%)   Group 2: liposomes   Group 3: niosomes	In vitro and ex in vitro drug release profiles of all the nanovesicule formulations showed a more extended drug release compared to the currently available commercial solution Efficacy was greater compared to the commercial product, whose activity was not sustained beyond 60 min	[154]
Eudragit-based brimonidine tartrate nanoparticle formulations (BRD-loaded ERS– ERL nanoparticles)	Eudragit nanoparticles	In vitro drug release studies In vivo pharmacodynamic studies (employing glaucomatous New Zealand rabbits): IOP-lowering efficacy studies performed by instillation of aqueous dispersion of nanoparticles and conventional eye drop solution	All the selected BRD-loaded ERS–ERL nanoparticles showed an extension of the drug release in vitro Results of in vivo pharmacodynamic efficacy studies of selected BRD-loaded ERS–ERL nanoparticle formulations and marketed BRD eye drops showed a similar peak IOP reduction, but prolonged IOP efficacy (marketed eye drops duration of 6 h compared to 36–72 h with the nanoparticles formulations)	[155]
BRD-loaded microspheres using poly(lactic acid) (PLA)	Microspheres	In vitro release kinetics of BRD In vivo experimental treatment groups (employing New Zealand rabbits):   Single microneedle injection of BRD-loaded microspheres into the supraciliary space   BRD (0.15%) commercial eye drops (administered three times a day to the upper conjunctival sac, for a week)	After topical delivery of BRD, a consistent IOP reduction of 2–4 mmHg was detected, but the IOP quickly returned to baseline after the interruption of the drops BRD-loaded microspheres high dose group (30% BRD-loaded microspheres) showed IOP reduction of the treated eye for 33 days, after a single injection into the supraciliary space	[156]
Optimized BRD-loaded chitosan (CS) and sodium alginate (ALG) nanoparticles	CS and ALG nanoparticles	In vitro studies (drug release and cytotoxicity assays) In vivo studies (mice strains BXD29 and BXD96): a single dose of the test formulations or commercial BRD eye drops (BRD 0.15%) were instilled into the inferior conjunctival sac	In vitro toxicity studies did not show significant differences between nano-based formulations and commercial BRD eye drops All nano-based formulations showed a greater sustained IOP-lowering effect compared to the commercial BRD. Time required for IOP to return to baseline ranged from 17.2 to 25.2 h for nano-based formulations, compared to 7–7.4 h for commercial BRD	[157]
BRD-loaded nanostructured lipid carriers	Nanostructured (NLC) and solid (SLN) lipid nanoparticles	In vitro drug release study Ex vivo permeability study In vivo studies (a single dose (50 µL) of lipid nanoparticles was instilled into the lower conjunctival sac of a normotensive albino rabbit). Ocular tolerance analysis, IOP measurements, and ocular histology were performed	Both NLCs and SLNs showed a biphasic release pattern. SLNs showed 61.74 ± 2.56% drug released after 2 h and 74.34 ± 0.14% after 6 h, while NLCs showed 66.89 ± 3.4% drug released after 2 h and 95.8 ± 2.31% after 6 h. Commercial BRD showed a unique burst release of 88.76 ± 1.78% within the first hour NLCs demonstrated a permeability coefficient 1.23-fold higher than that of SLNs Peak IOP lowering with NLCs, SLNs, and commercial BRD eye drops was 13.14 ± 1.28, 10.03 ± 0.32, and 7.84 ± 1.04 mmHg, respectively The peak IOP effect occurred after 6 h for NLCs, after 4 h for commercial BRD, and after 2 h for SLNs NLCs and SLNs were found in the anterior chamber of treated eyes, indicating that lipid nanoparticles penetrate through the cornea	[158]
BRD-loaded microspheres/carrier system (M/CS)	Microspheres poly(d,l-lactic-co-glycolic acid) (PLGA)	In vitro release studies In vivo studies (IOP measurements after BRD-loaded M/CS subconjunctival implantation in normal and glaucomatous eyes)	After a single dose of the BRD-loaded M/CS, an IOP reduction of 20 mmHg was achieved after 1 day, and was sustained over a period of 55 days M/CS structure remained intact for easy removal after BRD was fully released, even as long as 70 days after implantation	[159]