Proniosomal gel-derived niosomes: an approach to sustain and improve the ocular delivery of brimonidine tartrate; formulation, in-vitro characterization, and in-vivo pharmacodynamic study

Abstract

Brimonidine tartrate (BRT) is a hydrophilic a 2 adrenergic agonist used for the treatment of glaucoma. Glaucoma is an ocular disease affecting the anterior segment of the eye requiring lifetime treatment. Owing to the obstacles facing ocular delivery systems and hydrophilicity of BRT, frequent administration of the eye drops is required. Niosomes have been widely used to improve the ocular bioavailability of the topically applied drugs and to enhance the ocular residence time. However, they have drawbacks as physical instability, aggregation, and loss of the entrapped drug. For this reason, BRT proniosomes were prepared to overcome niosomal instability issues. A D-optimal design was utilized to determine the optimum conditions for preparation of the proniosomal gels. Independent variables were amount of surfactant, surfactant:cholesterol ratio, and type of surfactant used. The dependent variables were entrapment efficiency (EE%), particle size, percentage of drug released after 2 h (Q 2h), and percentage of drug released after 24 h (Q 24h). The optimum formula was suggested with desirability 0.732 and the composition of 540 mg Span 60 and 10:1 surfactant:cholesterol ratio. The results obtained after reconstitution were; EE% of 79.23 ± 1.12% particle size of 810.95 ± 16.758 nm, polydispersity index (PDI) 0.6785 ± 0.213, zeta potential 59.1 ± 0.99 mV, Q 2h 40.98 ± 1.29%, Q 8h 63.35 ± 6.07%, and Q 24h ¼ 91.11 ± 1.76%. Transmission electron microscope imaging of the formula showed the typical spherical shape of niosomes. In-vivo pharmacodynamic study assured the improved ocular bioavailability of BRT selected formula when compared with Alphagan V R P with relative AUC 0-24 of 5.024 and 7.90 folds increase in the mean residence time (MRT). Lack of ocular irritation of the formula was assured by Draize test.

Development of Provesicular Nanodelivery System of Curcumin as a Safe and Effective Antiviral Agent: Statistical Optimization, In Vitro Characterization, and Antiviral Effectiveness

“…These results are in accordance with Eldeeb et al [67] who studied the optimal conditions for the formulation of brimonidine tartrate-loaded proniosomes and found that the EE% of Span 60based proniosomes was higher than Tween 80-based ones. Figure 4 demonstrates that the Q12h of different Curcumin-loaded proniosomes ranged from 42.71 ± 1.74 to 94.91 ± 2.18%.…”

Formulation and Characterization of Acetazolamide/Carvedilol Niosomal Gel for Glaucoma Treatment: In Vitro, and In Vivo Study

“…Stirring was continued until the formation of gel base then left overnight for equilibration. Gel formulations were prepared by mixing the niosomal dispersions with the gels by a glass rod to have a final combination niosomes gel [27]. The prepared formulae were examined for their physical characteristics such as color, clarity, and homogeneity.…”

Niosomal Drug Delivery Systems for Ocular Disease—Recent Advances and Future Prospects

“…Glaucoma is considered as a neurodegenerative disease and often requires a lifetime treatment [ 55 , 110 , 111 ]. Glaucoma is an optic neuropathy that is characterized with retinal ganglion cell (RGC) death by apoptosis, resulting in degeneration of nerve axons and visual field defects [ 110 , 112 , 113 ].…”

“…The most prevalent factor associated with Primary Open Angle Glaucoma prognosis is the increased intraocular pressure (IOP) [ 110 , 113 , 114 ]. IOP rises because of the accumulation of aqueous humor in the anterior chamber, which might be due to the overproduction of fluid or the blockage of drainage system [ 55 ]. The elevated IOP causes an imbalance in the retinal blood flow, which leads to the degeneration of the optic nerve [ 55 ].…”

“…IOP rises because of the accumulation of aqueous humor in the anterior chamber, which might be due to the overproduction of fluid or the blockage of drainage system [ 55 ]. The elevated IOP causes an imbalance in the retinal blood flow, which leads to the degeneration of the optic nerve [ 55 ]. The mainstream treatment method for glaucoma is to reduce the intraocular pressure by various treatment options including drugs, laser treatment, and surgery [ 114 , 115 ].…”