Liposomes as a Novel Ocular Delivery System for Brinzolamide: In Vitro and In Vivo Studies

Abstract

ABSTRACT. The objective of this study was to investigate the potential of liposomes as an ophthalmic delivery system for brinzolamide (Brz) to enhance the local glaucomatous therapeutic effect. The liposomes of Brz (Brz-LPs) were produced by the thin-film dispersion method with a particle size of 84.33± 2.02 nm and an entrapment efficiency of 98.32±1.61%. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) analysis proved that Brz was successfully entrapped into Brz-LPs. Brz-LPs displayed a biphasic release pattern in vitro with burst release initially and sustained release afterwards. The corneal permeability was measured using modified Franz-type diffusion cells, and Brz-LPs showed 6.2-fold increase in the apparent permeability coefficient when compared with the commercial available formulation (Brz-Sus). Moreover, Brz-LPs (1 mg/mL Brz) showed a more sustained and effective intraocular pressure reduction (5-10 mmHg) than Brz-Sus (10 mg/mL Brz) in white New Zealand rabbits. Therefore, Brz-LPs were a hopeful formulation of Brz for glaucoma treatment and worthy of further investigation.

Delivery of therapeutics for deep-seated ocular conditions – status quo

“…[1] Commercial suspensions used in treating ocular conditions such as glaucoma-related pathology has its limitations, some of which include low patient compliance as it produces an uncomfortable feeling and undesirable tear production that can wash away the drug when used. [34] The use of liposomes can overcome the aforementioned limitations by increasing the drug's residence time at the site of action and it also has intraocular pressure-lowering efficacy which may add to the therapeutic effect of treating ocular conditions that require the reduction of intraocular pressure. [34] However, liposomes do present certain limitations, some of which may include increased cost to formulate, scale-up issues, as well as a low reproducibility where it can be difficult to reproduce the same liposome with the same properties as intended.…”

“…[34] The use of liposomes can overcome the aforementioned limitations by increasing the drug's residence time at the site of action and it also has intraocular pressure-lowering efficacy which may add to the therapeutic effect of treating ocular conditions that require the reduction of intraocular pressure. [34] However, liposomes do present certain limitations, some of which may include increased cost to formulate, scale-up issues, as well as a low reproducibility where it can be difficult to reproduce the same liposome with the same properties as intended. [2] Another limitation also includes the instability of the macromolecules during the production stage of the liposome, where the macromolecule properties may not stay the same throughout the formulation period.…”

New technologies of hypotensive drug delivery in glaucoma treatment

“…Многим исследователям представляется перспективным для доставки гипотензивных препаратов использовать комбинации полимеров и коллоидных систем: липосом [22][23][24][25][26], ниосом [27,28], кубосом [29], микроэмульсий [30], наноэмульсий [31][32][33] и наночастиц [34][35][36][37][38][39][40]. За счет медленного высвобождения лекарственных препаратов удается значительно пролонгировать время нахождения активного вещества в глазу.…”

Development and Validation of Simple Uv Spectrophotometric Method for Estimation of Brinzolamide

“…Glaucoma is the term used for a group of ophthalmic disorders characterized by an increase in intraocular pressure (IOP), which results in damage to the optic disc and visual field disturbances leading to an imbalance between the production and drainage of aqueous humor 1 . Brinzolamide (BRZ), one of the carbonic anhydrase inhibitors, is effective in reducing IOP for glaucoma therapy mainly through decreasing the production of the aqueous humor 2 . Brinzolamide (BRZ), chemically (R) -4-(ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H thienol (3,2-e) -1,2thiazine-6-sulphonamide 1,1-dioxide, (Figure 1) is a highly specific, non-competitive reversible carbonic anhydrase inhibitor, which is indicated for patients with ocular hypertension or open-angle glaucoma, a condition associated with an elevated intraocular pressure in the eye.…”