ABSTRACT
Drugs are commonly applied to the eye for a localized action on the surface or in the anterior segment of the eye. However, drug delivery in ocular therapeutics is a challenging problem especially if the compound is lipophilic. Due to physiological and anatomical constraints, only a small fraction of the administered drug in eye drops is ocularly absorbed (1-3). The cornea is comprised of three layers, which account for its poor permeability characteristics: (i) the outer epithelium, which is lipophilic, (ii) the stroma, which constitutes 90% of the thickness of the cornea and is hydrophilic, and (iii) the inner endothelium consisting of a single layer of flattened epithelium-like cells. Because the cornea has both hydrophilic and lipophilic structures, it presents an effective barrier to the absorption of both hydrophilic and lipophilic compounds. The compounds that penetrate the cornea best exhibit a log P octanol/water of two (4). Furthermore, for the treatment of different extra-and intra-ocular etiological conditions such as glaucoma, uveitis, keratitis, dry eye syndromes, cytomegalovirus retinitis, acute retinal necrosis, proliferative vitreoretinopathy, macular degenerative disease, etc., several lipophilic and poorly water soluble drugs have become available in recent years. These drugs represent a formulation challenge for scientists who design simple eye drop aqueous solutions because of aqueous solubility limitations. In addition, daily administrations are needed and most of the traditional ophthalmic dosage forms are clearly not only uncomfortable for the patient but also not efficient in combating some of the current virulent ocular diseases especially of the posterior segment. Therefore, lipid and polymeric colloidal carriers are more and more in demand to overcome the drawbacks of aqueous medicated collyres for the treatment of different extra-and intra-ocular etiological conditions. They are being explored to improve the bioavailability and duration of therapeutic action of ocular
drugs. It is now recognized that severe ocular diseases, mainly of the back of the eye, cannot be treated by topical administration of the conventional ocular aqueous dosage forms (5). The most plausible alternative to improve delivery of active ingredients, in particular the lipophilic compounds, is the use of lipid or polymeric colloidal carriers. It is estimated that 40% or more of bioactive substances being identified through combinatorial screening programs are poorly soluble in water (6,7). Consequently, the drug molecules belonging to these categories cannot be easily incorporated into aqueous-cored/based eye drop dosage forms at adequate concentrations, and thus, the clinical efficacy of highly lipophilic drugs is being impeded. Dosage forms for ocular topical application of lipophilic drugs consist of oil drops, lotions, ointments, gels, and ocular systems, most of them being still ineffective and uncomfortable to the patients (8). Thus, lipid and polymeric colloidal particles represent an attractive alternative to efficiently deliver active ingredients especially if they are lipophilic and often exhibit hydrophobic character.
