A New Preparation Method for Ophthalmic Drug Nanoparticles

The eye is a small and complex organ that is separated from the rest of the body by multiple layers of biological barriers. Moreover, the internal ocular structures and tissues are protected from the external environment by the tight junctions of the corneal epithelium and the mucosal surface. The ophthalmic application of drugs is the primary route of administration for the treatment of various eye diseases, and is well-accepted by patients; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers and dilution caused by lacrimation [1-3]. Consequently, there is a need for the frequent instillation of concentrated solutions to obtain the desired therapeutic effect in both the anterior and posterior hemispheres of the eye. However, the frequent administration of drugs can cause corneal damage as well as undesirable side effects resulting from the systemic absorption of drugs through the nasolacrimal duct [4,5]. Therefore, the primary challenge for ocular drug delivery is how to circumvent these protective barriers in order to achieve therapeutically effective concentrations of drugs in the intraocular tissues. In this regard, it is very important to increase the effectiveness of drugs by enhancing their bioavailability [6]. In order to overcome these problems and increase ocular drug bioavailability, several strategies including the preparation of viscous solutions, micro/nanoparticles and hydrogels have been developed and investigated [1,4,7-10]. In the case of viscous solutions, numerous studies have demonstrated that they do not possess sufficient mechanical strength to resist the ocular clearance mechanism, and offer only a transient improvement in ocular residence time [11,12]. On the other hand, it has been reported that the capability of drugs to penetrate across the cornea can be significantly improved by decreasing the particle size using nanoparticles [3,9,13-15]. Ophthalmic formulations containing drug nanoparticles present a possible solution to the limitations surrounding ocular drug penetration [16-19], and it is known that decreasing direct cellular stimulation and reducing the amount drug used by increasing its bioavailability are useful ways to circumvent the side effects related to drug delivery [6]. It is expected that ophthalmic drug systems using nanoparticles may provide an alternative strategy for increasing ocular drug penetration [16-19]. This review addresses the usefulness of ophthalmic formulations containing drug nanoparticles. In addition, we introduce the new method for the preparation of drug solid nanoparticles. Abstract