Enhancing strategies to promote macromolecules transport across ocular barriers

The development of new biological drugs, for the treatment of diseases of the anterior and posterior eye segment, has posed different problems to drug delivery technologies as their unfavourable physico-chemical characteristics render these molecules poorly permeable through ocular tissues. A brief introduction about anatomical barriers of the eye, different administration routes, limitations associated to the ophthalmic delivery of biologics and suitable delivery platforms for overcoming them are presented in Chapter 1. The investigation of the influence of macromolecules related factors on their diffusion across ocular membranes is discussed in Chapter 3. This chapter is focused on the comparison between two model proteins (lysozyme and cytochrome c, with similar molecular weight and net charge at physiological pH) permeability and the feasibility of the application of transscleral iontophoresis for enhancing proteins transport. Cyclosporine (1.2 kDa) delivery to the eye has been investigated by the use of polymeric micelles and ophthalmic inserts. Chapter 4 is focused on the development and characterization of a novel micellar formulation made of poloxamer 407 and TPGS for cyclosporine targeting both the anterior and the posterior eye segment. Details about the characterization of micelles in terms of particle size, morphology, ocular irritancy, rheology and ex vivo penetration performance though porcine ocular tissues are provided. Finally, preliminary results about the development of a novel ophthalmic insert of hyaluronic acid and hydroxypropyl-?-cyclodextrin for cyclosporine topical ocular delivery is presented in Chapter 5.