Ricerc@Sapienza

Intracellular pathogens are a critical challenge for antimicrobial therapies. Staphylococcus aureus (S. aureus)
causes approximately 85% of all skin and soft tissue infections in humans worldwide and more than 30% of
patients develop chronic or recurrent infections within three months, even after appropriate antibacterial
therapies. S. aureus is also one of the most common bacteria found in chronic wounds. Recent evidences suggest
that S. aureus is able to persist within phagolysosomes of skin cells (i.e. keratinocytes, phagocytic cells), being

Highly hydrophilic and biocompatible nanocarriers based on polysaccharide hydrogels (nanohydrogels,
NHs) were shown to be promising systems for drug delivery applications. Following the idea of these
emerging drug carriers, the aim of the present work was to develop self-assembled hydrogel nanoparticles
based on amphiphilic derivatives of hyaluronic acid (HA) and riboflavin (Rfv), synthesized by “click”
Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) reaction. The obtained amphiphilic product

Although in recent years several methods have been studied and developed to obtain different types of nanosized drug delivery systems, the set up of suitable procedures and materials remains highly expensive, their preparation is time consuming and often not feasible for a scale-up process. Furthermore, the sterilisation and storage of nanocarrier formulations represents a complicated but mandatory step for their effective use.

Nanohydrogels based on natural polymers, such as polysaccharides, are gaining interest as vehicles for therapeutic agents, as they can modify the pharmacokinetics and pharmacodynamics of the carried drugs. In this work, hyaluronan-riboflavin nanohydrogels were tested in vivo in healthy rats highlighting their lack of toxicity, even at high doses, and their different biodistribution with respect to that of native hyaluronan.

Hyaluronan (HA) is among the most important bioactive polymers in mammals, playing
a key role in a number of biological functions. In the last decades, it has been increasingly studied
as a biomaterial for drug delivery systems, thanks to its physico-chemical features and ability to
target and enter certain cells. The most important receptor of HA is ‘Cluster of Differentiation 44’
(CD44), a cell surface glycoprotein over-expressed by a number of cancers and heavily involved in

Staphylococcus aureus is one of the most significant human pathogens that is frequently isolated in a wide range of superficial and systemic infections. The ability of S. aureus to invade and survive within host cells such as keratinocytes and host immune cells has been increasingly recognized as a potential factor in persistent infections and treatment failures. The incorporation of antibiotics into hyaluronan-cholesterol nanohydrogels represents a novel paradigm in the delivery of therapeutic agents against intracellular bacteria.

Natural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive molecules that show a number of therapeutic effects. However, their applications are remarkably limited by their poor water solubility, physico-chemical instability and low bioavailability.