Controlling antibiotic release kinetics is essential for effective treatment and for many biomedical applications. Herein, silica nanoparticles were prepared and loaded with gentamicin through various routes (Layer-by-layer (LbL), entrapment, adsorption). LbL coatings involved the polyelectrolytes poly(styrene sulfonate) (PSS) and Poly(allylamine hydrochloride) (PAH), where the nanoparticles coated with quadruple layers (QL) of [PSS/gentamicin/PSS/PAH]. The nanoparticles were characterized by zeta potential, transmission electron microscope (TEM) and thermogravimetric analysis (TGA). Moreover, nanoparticles' gentamicin release was tested in different release media (acetate buffer pH 5 and PBS pH 7.4). The gentamicin LbL-coated nanoparticles were successful to sustain drug release over 2 weeks. Although the entrapment method was similarly able to sustain drug release over two weeks, it showed lower drug loading when compared to the LbL-coated nanoparticles. In contrast, simple adsorption on bare silica surface resulted in significantly lower drug loading and 90 % release on day 1. The release of gentamicin showed pH-responsive behavior, with higher release at pH 5. This work demonstrates that gentamicin release from silica nanocarriers can be controlled by the different approaches for loading gentamicin. This will give different release profiles tailored for many biomedical applications such as antibiotic-loaded bone cement or implant coatings.