Cell penetrating peptides in ocular drug delivery: State of the art.

Despite the increasing number of effective therapeutics for eye diseases, their treatment is still challenging due to the presence of effective barriers protecting eye tissues. Cell Penetrating Peptides (CPPs), synthetic and natural short amino acid sequences able to cross cellular membrane thanks to a transduction domain, have been proposed as possible enhancing strategies for ophthalmic delivery. In this review, a general description of CPPs classes, design approaches and proposed cellular uptake mechanisms will be provided to the reader as an introduction to ocular CPPs application, together with an overview of the main problems related to ocular administration. The results obtained with CPPs for the treatment of anterior and posterior segment eye diseases will be then introduced, with a focus on non-invasive or minimally invasive administration, shifting from CPPs capability to obtain intracellular delivery to their ability to cross biological barriers. The problems related to in vitro, ex vivo and in vivo models used to investigate CPPs mediated ocular delivery will be also addressed together with potential ocular toxicity issues.

Perfluoropolyether phosphate: skin exfoliation after a topical pre-treatment, TEWL and skin elasticity, by in-vivo non-invasive methods.

Glycolic acid (GA) and other alpha-hydroxyacids (AHAs) are common ingredients of products designed to accelerate exfoliation of the skin. It is known that acidic pHs are essential in order to increase the efficacy of AHA-based products. The formulator is, therefore, obliged to achieve a difficult balance between performance (skin exfoliation) and risks (skin irritation). In order to overcome this problem, many common organic acids, and combinations of them, have been proposed, with marginal improvements. The need for a new chemistry, in order to achieve better results, was evident, particularly from the point of view of safety. We decided, therefore, to investigate the efficacy of perfluoropolyether (PFPE) phosphate, a new acidic material, already proposed for lowering the pH without increasing skin irritation. Two gels containing PFPE phosphate at different pH values (3 and 7), an acidic gel containing GA at pH 3, and a neutral gel, without an active compound, were applied on 20 healthy volunteers and evaluated with regard to effects on the skin: *Exfoliation after a topical pre-treatment with these gels *Transepidermal water loss (TEWL) and elasticity The main conclusion of the investigation was that PFPE phosphate has effects, particularly skin exfoliation rate, quite independent of the pH, and comparable to the gel containing GA at pH 3, apparently without the typical drawbacks of AHAs.

Alpha-tocopherol pro-vitamins: synthesis, hydrolysis and accumulation in rabbit ear skin.

We synthesized esters of alpha-tocopherol (VE) with the aim to develop new pro-vitamins, easily reconverted by enzymes in the skin and able to release another active moiety such as an amino acid, in order to obtain a synergic effect. In particular, the attention was dedicated to the amino acids glycine and alanine and to pyroglutamic acid. The sensitivity of pro-vitamins to enzymatic hydrolysis was evaluated in vitro using porcine liver esterase. Permeation experiments were performed using rabbit ear skin, for the quantification of pro-vitamins and derived VE in the epidermis and dermis. The new derivatives synthesized, and in particular the glycine and alanine derivatives, accumulated in rabbit skin in a significant extent and originated substantial amounts of alpha-tocopherol. In comparison with the acetate derivative (VEAc), the amounts accumulated are comparable or higher. Moreover, the new derivatives, being more hydrophilic, allow the use of vehicles such as the mixture water/propylene glycol/ethanol widely employed for the preparation of creams and gels. Finally, the enzymatic metabolism of these new derivatives generates not only VE, but also components that can have a further advantageous action on skin.