Nanotechnology applied to medicine is the new frontier of drug therapy that aims to create personalized, safer and more effective treatments. Nano-structured systems that can facilitate the penetration, the site-specific transport and controlled release of a drug, improving efficiency and reducing the unwanted side effects, could have evolutionary implications for pharmacotherapy. This explains the great interest of the academic and industrial research in drug delivery nanotechnology. This technology, which allows to reevaluate and reformulate known drugs, is more advantageous in terms of cost, time and risk than drug discovery, and for the pharmaceutical industry is an important strategy to maintain market competitiveness. Ophthalmic diseases lack of effective therapies and the research for improving the bioavailability of a drug is of particular interest for the ophthalmic industry. The eye for its anatomical structure is a protected organ, the cornea and the blood-retinal barrier restrict the passage to many drugs administered topically or systemically. This segregation is a valid defense because it reduces the occurrence of iatrogenic effects, but also a definite disadvantage in the treatment of an eye disease. About 90% of the ophthalmic solutions intended for the anterior segment of the eye is lost by nasolacrimal drainage and systemic absorption via the conjunctiva, and the therapy of posterior segment diseases is currently based mainly on intravitreal injections with high risk of side effects. Although in the last thirty years, some progress has been made in the ophthalmic industry with the development of new devices for delivery and controlled and sustained release of drugs such as gel in situ, implants, contact and intraocular lenses, micro- and nano-emulsions, much remains to be done to improve the chemical and chemo-physical properties, the pharmacokinetic and pharmacodynamic, the therapeutic index and the compliance of many ocular drug formulations.
In this context, the Supramolecular Chemistry research group of the Institute of Biomolecular Chemistry in Catania, has made a nanocarrier, generated by the spontaneous self-assembly of an amphiphilic cationic calix[4]arene in phosphate buffered saline, suitable as vehicle for different drugs of ophthalmic interest, affected by easy degradability, low solubility and scarce bioavailability. The formulations formed by the calixarene nanocarrier and the selected drug satisfy the chemical, chemo-physical and pre-industrialization requirements which a eyepiece drug delivery system must meet: size smaller than 100 nm, low polydispersity index, positively charged surface to increase adhesion and eye surface permanence, simple and reproducible preparation protocol, good percentage of drug loading, protection of the drug from degradation, stability, sterilizability and lyofilizability. The collaboration with researchers of CNR-IBIM, University of Messina and ophthalmic industry SIFI SpA has allowed us to evaluate the biocompatibility, ocular tolerability and the pharmacological activity of the formulations in vivo models of uveitis, diabetic retinopathy, age-related macular degeneration and glaucoma. The results suggest that the calixarene macrocycles could represent innovative molecular scaffolds alongside the most famous polymers and cyclodextrins in building up new preservative free eye drops for the treatment of disease of the anterior and posterior segment of the eye.
This research was funded by the project "Hippocrates Development of Micro and Nano Technologies and Advanced Systems for Human Health" - PON02_00355_2964193 "Patent Application:" Nanostructured FORMULATIONS for the delivery of silibinin and other active ingredients for treating ocular diseases "PCT/IB2015/057732.
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