Fabrication and efficacy of poly (beta-amino esters)-based nanoparticles to enhance antimicrobial agents delivery to orthopaedic acquired infections sites

In this work a novel delivery system was developed to provide a targeted and continuous release of therapeutic molecules that could have a range of biomedical possible applications. Physico-chemical and material characterisation of the developed system was conducted alongside with a drug release quantification

Role of poly-beta-amino-esters hydrolysis and electrostatic attraction in Gentamicin release from Layer-by-Layer coatings

Layer-by-layer (LbL) deposition is a versatile techniques that has been employed in numerous industrial applications i.e. biomaterials, drug delivery and electronics to confer peculiar properties to the system. When employed in 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 in LbL on medical devices. Their use allowed 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 PBAE 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 coating on the surface of silica nanoparticles entrapping gentamicin as model drug and demonstrated that the drug release from PBAE containing LbL coating is predominantly controlled by the electrostatic attractions between opposite charged electrolytes. The positive charge of PBAE decreases from pH5 to pH7.4 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 pH5; 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