Comparison of different models for the testing of pilocarpine eyedrops using conventional eyedrops and a novel depot formulation (nanoparticles)

Abstract

An objective in the development of ophthalmic formulations is the use of in vitro or animal models that closely resemble the clinical situation. For this reason, experiments with conventional pilocarpine nitrate eyedrops and a depot formulation of pilocarpine nitrate sorbed to poly (butylcyanoacrylate) nanoparticles were carried out. In vitro, the diffusion of pilocarpine through bovine cornea was measured using Edelhauser cells. In vivo, the rabbit aqueous humor concentration of pilocarpine and miosis were determined after application of the above formulations. In addition, intraocular pressure was measured. Since pilocarpine has little influence on intraocular pressure in healthy rabbits, the pressure had to be increased artificially. Three models were employed that are described in the literature, namely, the betamethasone model, the alpha-chymotrypsin model, and the water-loading model. Pilocarpine could be loaded onto nanoparticles by 15% but was rapidly released from the nanoparticles based on the bovine corneal experiment. Nanoparticles only enhanced the aqueous humor concentration at 30 min; this increase, however, led to a considerably extended period of miosis as well as a reduction in intraocular pressure. The duration of the action and the intensity of the response were different among the three models tested. According to the present results, the betamethasone model seems to represent the best correlation to the clinical situation.

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“…Protein nanoparticles as carriers for ophthalmic drugs: Protein nanoparticles exhibit a considerably longer half-life in the eye than eye-drops. Pilocarpine bound to gelatin nanoparticles substantially prolonged the intraocular pressure reduction in rabbits with experimental glaucoma as well as the miosis time 21 in comparison to a pilocarpine eye-drop solution.…”

New Techniques for Drug Delivery to the Posterior Eye Segment

“…Ocular administration of nanoparticles has been widely investigated as a topical suspended system or a local injectable system for treating various eye disorders, such as glaucoma (41)(42)(43)(44)(45), ocular infections (46)(47)(48), ocular inflammations (49-51) and immune-mediated ocular disorders (52)(53)(54). Drug-loading capacity, drug release rate and biocompatibility of the polymer are of utmost importance for a successful treatment.…”

Drug targeting with nanoparticles

“…Other uses of nanoparticles include peroral (27), ophthalmic (28), lymphatic administration (29), and their use as adjuvants of vaccines (1,2). After peroral administration they enhanced the bioavailability of a number of drugs including vincamine, insulin (1,2) and avarol (30).…”

“…After peroral administration they enhanced the bioavailability of a number of drugs including vincamine, insulin (1,2) and avarol (30). In the eye the reduction of the intraocular pressure was prolonged very considerably after administration of pilocarpine bound to nanoparticles compared to the aqueous solution (28). The use of nanoparticles as an adjuvant for vaccines enhanced the antibody response against a number of antigens and the protection against infection (1,2).…”