Layer-by-layer (LbL) deposition is a versatile technique that has been employed in numerous industrial applications i.e. biomaterials, drug delivery and electronics to confer peculiar properties to the system. When LbL is employed for drug delivery, the active molecule is sandwiched between layers of polyelectrolytes and the release is controlled by the diffusion of the drug through the layers and the possible hydrolysis of the coating (delamination). Poly-beta-amino-esters (PBAEs) are a class of hydrolysable polyelectrolytes that have been widely used in DNA delivery and for LbL on medical devices. Their use allowed the controlled release of antibiotics and other bioactive compounds from the surface of medical devices without cytotoxic effects. The general accepted consensus is that drug released from LbL coating assembled using PBAEs is the results of the polymer hydrolysis; however, no attention has been paid to the role of the electrostatic attraction between PBAE and the other polyelectrolyte utilised in the LbL assembly. In this work, we prepared LbL coatings on the surface of silica nanoparticles entrapping gentamicin as model drug and demonstrated that the drug release from PBAEs containing LbL coatings is predominantly controlled by the electrostatic attraction between opposite charged electrolytes. The positive charge of PBAE decreased from pH = 5 to pH = 7.4 while alginate negative charges remained unchanged in this pH range while PBAE hydrolysis kinetics was faster, as determined with Gel Permeation Chromatography (GPC), in acidic conditions. When PBAE were employed in the LbL construct higher levels of drug were released at pH = 7.4 than at pH = 5; additionally, replacing PBAE with chitosan (the charge of chitosan is not influenced in this pH range) resulted in comparable gentamicin release kinetics at pH = 5. (C) 2018 Elsevier Inc. All rights reserved.