Methazolamide Calcium Phosphate Nanoparticles in an Ocular Delivery System

Abstract

A new system for the local delivery of methazolamide to the eye has been developed based on calcium phosphate (CaP) nanoparticles. The methazolamide loaded CaP nanoparticles were prepared through the formation of an inorganic core of CaP and further adsorption of the methazolamide. The maximum loading of methazolamide studied using UV-vis spectrophotometry was about 0.2％ (w/w). The drug-loaded particles had a negative surface charge at about -30 mV while their mean particle diameter was estimated to be 256.4 nm. In vitro release studies demonstrated diŠusion-controlled release of methazolamide from the CaP nanoparticles over a period of 4 h. In vivo studies indicated that the intraocular pressure (IOP)-lowering eŠect of the inorganic nanoparticle eye drops lasted for 18 h, which was signiˆcantly better than the eŠect of 1％ brinzolamide eye drops (6 h). Physical stability studies indicated that the preparation was stable for 6 months at 40°C. Theseˆndings suggested that methazolamide bound to CaP nanoparticles might be useful in the local treatment of glaucoma.

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

“…For example, topical administration of nanoparticles (256 nm) containing the carbonic anhydrase inhibitor methazolamide lowered IOP for 18 hours, with the maximal effect observed 2 to 8 hours after dosing. 36 In vitro drug release studies, however, showed that 99% of the drug had been released from the nanoparticle after 4 hours, suggesting a ''burst'' of drug rather than sustained release. 36 Similarly, brimonidine-loaded nanoparticles (117 to 131 nm) delivered via eye drops lowered IOP for 5 to 7 hours after dosing.…”

“…36 In vitro drug release studies, however, showed that 99% of the drug had been released from the nanoparticle after 4 hours, suggesting a ''burst'' of drug rather than sustained release. 36 Similarly, brimonidine-loaded nanoparticles (117 to 131 nm) delivered via eye drops lowered IOP for 5 to 7 hours after dosing. 37 The amount of brimonidine released in vitro after 24 hours ranged from 37% to 62%.…”

“…[30][31][32][33][34][35] Given the issues with patient compliance in glaucoma, the use of nanoparticles to deliver a controlled, sustained release of therapeutics to the retina or other ocular structures via topical drops, contact lenses, and intravitreal injection could drastically reduce the number of patients who have progression to vision loss in this disease. [36][37][38][39] To address the need for extended-release treatments that minimize patient nonadherence and discomfort, we examined the efficacy of four types of nanoparticleencapsulated compounds, or nanosponges (NS), administered intravitreally to lower IOP in mice with microbead-induced ocular hypertension. A series consisting of organic, fully degradable polyester NS differing in their nanoscopic size dimension (50, 400, and 700 nm) and crosslinking density (7% and 14%) were synthesized to create a polymeric network for ocular hypotensive drug entrapment and to influence release and solubility in the physiological environment.…”

Recent Patents on Ophthalmic Nanoformulations and Therapeutic Implications

“…Calcium phosphate (CaP) nanoparticles have shown great applications in drug delivery systems due to biocompatibility (non-toxic degradation products constitute the inorganic part of human hard tissue) [36]. As inorganic CaP nanoparticles were found to be chemically stable, they were found to ensure the maintenance of desired pharmacological action [36].…”

“…As inorganic CaP nanoparticles were found to be chemically stable, they were found to ensure the maintenance of desired pharmacological action [36]. The successful development calcium phosphate particle as an ocular drug delivery system was demonstrated in patent disclosure (WO2004050065A1) by Biosante Pharmaceuticals [37].…”