Ricerc@Sapienza

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
HA endocytosis. Moreover, CD44 is highly expressed by keratinocytes, activated macrophages and
fibroblasts, all of which can act as ‘reservoirs’ for intracellular pathogens. Interestingly, both CD44 and
HA appear to play a key role for the invasion and persistence of such microorganisms within the cells.
As such, HA is increasingly recognised as a potential target for nano-carriers development, to pursuit
and target intracellular pathogens, acting as a ‘Trojan Horse’. This review describes the biological
relationship between HA, CD44 and the entry and survival of a number of pathogens within the cells
and the subsequent development of HA-based nano-carriers for enhancing the intracellular activity
of antimicrobials.