Antimicrobial peptides (AMP) and cell-penetrating peptides (CPP) are two classes of
peptides that share some structural and physicochemical similarities. Antennapedia or
penetratin (ANT) is one of the most known CPPs, that was proven to have antimicrobial activity
against certain strains of planktonic bacteria. ANT can enter the cells but has no activity
against intracellular bacteria. This is attributable to the inability of the peptide to reach
bacteria reside within cellular components as well as low delivery efficiency, due to loss of
activity by proteolysis and poor specificity. The aim of this work is to develop a formulation that
can effectively reach and attack intracellular bacteria. To achieve this goal, ANT was
encapsulated in PLGA platform as nanoparticles with the size range of 500-1000 nm, which
allows for selective uptake by macrophages where bacteria mostly reside. ANT was loaded with
high loading efficiency (12.7%) inspite of high water solubility. ANT-nanoparticles (ANT-NP)
had no cytotoxicity on J774a.1 macrophages and were readily taken up by macrophages as
confirmed by fluorescence microscopy. Antibacterial activity of ANT-NP remains to be tested
against different intracellular bacteria.