Two-photon microscopy as a visual tool for polymer compatibilization monitoring: the PE-EVOH case

: In this study, we present two-photon microscopy (2PM) as an original technique to investigate the compatibilization between PE-HEMA and EVOH at the sub-micrometer level, both on the surface and in the bulk. 2PM is a nonlinear fluorescence imaging technique commonly exploited for thick biological tissue analysis. Here, we use 2PM to visualize polymer blending through 3D images of the obtained films. Compatibilization was performed in solution, upon functionalization of PE-HEMA with 1.4% molar of ODIN, a fluorescent molecule able to form multiple hydrogen bonds with EVOH and to act as a fluorescent probe. Different blends were synthesized, and the obtained films were analyzed by 2PM. For all compositions, it was demonstrated that ODIN is evenly distributed both on the surface and in the bulk. 2PM analysis of the thermally reprocessed specimen revealed that repeated reprocessing allows the reformation of ODIN dimers as the most stable H-bonding array in the solid state, partially reversing the compatibilization

Hyaluronic acid - PVA films for the simultaneous delivery of dexamethasone and levofloxacin to ocular tissues

: Ocular drug delivery is challenging due to the poor drug penetration across ocular barriers and short retention time of the formulation at the application site. Films, applied as inserts or implants, can be used to increase residence time while controlling drug release. In this work, hydrophilic films made of hyaluronic acid and two kinds of PVA were loaded with dexamethasone (included as hydroxypropylcyclodextrin complex) and levofloxacin. This association represents one of the main treatments for the post cataract surgery management, and it is also promising for eye infections with pain and inflammation. Films were characterized in terms of swelling and drug release and were then applied to porcine eye bulbs and isolated ocular tissues. Film swelling leads to the formation of either a gel (3D swelling) or a larger film (2D swelling) depending on the type of PVA used. Films, prepared in an easy and scalable method, demonstrated high loading capacity, controlled drug release and the capability to deliver dexamethasone and levofloxacin to the cornea and across the sclera, to potentially target also the posterior eye segment. Overall, this device can be considered a multipurpose delivery platform intended for the concomitant release of lipophilic and hydrophilic drugs

Cyclosporine-loaded micelles for ocular delivery: Investigating the penetration mechanisms

Cyclosporine is an immunomodulatory drug commonly used for the treatment of mild-to-severe dry eye syndrome as well as intermediate and posterior segment diseases as uveitis. The ocular administration is however hampered by its relatively high molecular weight and poor permeability across biological barriers. The aim of this work was to identify a micellar formulation with the ability to solubilize a considerable amount of cyclosporine and promote its transport across ocular barriers. Non-ionic amphiphilic polymers used for micelles preparation were tocopherol polyethylene glycol 1000 succinate (TPGS) and Solutol® HS15. Furthermore, the addition of alpha-linolenic acid was assessed. A second aim was to evaluate micelles fate in the ocular tissues (cornea and sclera) to shed light on penetration mechanisms. This was possible by extracting and quantifying both drug and polymer in the tissues, by studying TPGS hydrolysis in a bio-relevant environment and by following micelles penetration with two-photon microscopy. Furthermore, TPGS role as permeation enhancer on the cornea, with possible irreversible modifications of tissue permeability, was analyzed. Results showed that TPGS micelles (approx. 13 nm in size), loaded with 5 mg/ml of cyclosporine, promoted drug retention in both the cornea and the sclera. Data demonstrated that micelles behavior strictly depends on the tissue: micelles disruption occurs in contact with the cornea, while intact micelles diffuse in the interfibrillar pores of the sclera and form a reservoir that can sustain over time drug delivery to the deeper tissues. Finally, cornea quickly restore the barrier properties after TPGS removal from the tissue, demonstrating its potential good tolerability for ocular application

Poly[(μ4-phenylphosphonato)zinc(II)]

The title two-dimensional coordination polymer, [Zn(C6H5PO3)]n, was synthesized serendipitously by reacting a tetraphosphonate cavitand Tiiii[C3H7, CH3, C6H5] and Zn(CH3COO)22H2O in a DMF/H2O mixture. The basic conditions of the reaction cleaved the phosphonate bridges at the upper rim of the cavitand, making them available for reaction with the zinc ions. The coordination polymer can be described as an inorganic layer in which zinc coordinates the oxygen atoms of the phosphonate groups in a distorted tetrahedral environment, while the phenyl groups, which are statistically disordered over two orientations, point up and down with respect to the layer. The layers interact through van der Waals interactions. The crystal studied was refined as a two-component twin