Double entrapment of growth factors by nanoparticles loaded into polyelectrolyte multilayer films

Abstract

Delivery of growth factors and control of vascularization are prominent problems in regenerative medicine.Vascular endothelial growth factor (VEGF) has been used both in vitro and in vivo to promote angiogenesis but due to its short half-life its controlled delivery is a sought after method. In this study we present a new concept of degradable drug loaded nanoparticles entrapped into exponentially growing multilayer films.Through hydrolysis of the nanoparticles, the drug can be delivered over long periods in a controlled manner. Poly(3-caprolactone) nanoparticles were loaded with VEGF and in turn the release of VEGF from a surface is controlled by a thick layer-by-layer polyelectrolyte film. Direct loading of VEGF inside the film was not efficient for long-term applications. When VEGF loaded nanoparticles were introduced into the film, the particles were equally distributed inside and were stable after several washes. Moreover, the presence of the film sustained the release of VEGF for 7 days. Addition of the nanoparticles to the film promoted endothelial cell proliferation, mainly due to the presence of VEGF. Mechanical properties of the film (Young's moduli) were also improved by the presence of nanoparticles. However, in the presence of the film loaded with nanoparticles and without any direct contact with this film, endothelial cell growth was also enhanced on polystyrene and on Transwell insert surfaces which demonstrates the effectiveness of the nanoparticles not only to improve the mechanical properties of the film but also to deliver active VEGF. An increase in nitric oxide levels as an indicator of endothelial cell activity was monitored and was correlated with the release of VEGF from the nanoparticle/film platform. Finally, such a system can be used as an auxiliary delivery body within implants to finely control the release of bioactive agent containing nanoparticles.

Immunomodulation with Self-Crosslinked Polyelectrolyte Multilayer-Based Coatings

“…Furthermore, it has been successfully used for the release of growth factors and drugs. [8][9][10][11] Degradation of these films via dissolution is an obstacle for achieving long-term release of cytokines, which can be improved by structures crosslinking. 12,13 Moreover, it is known that crosslinking these PLL/HA films strongly increase viability of cells growing on the films, mainly due to an increase of Young modulus.…”

Harnessing the Multifunctionality in Nature: A Bioactive Agent Release System with Self‐Antimicrobial and Immunomodulatory Properties

“…[ 13 ] Polyelectrolyte multilayers are versatile nano to microscale coatings that have been used widely as delivery systems. [14][15][16][17] Consecutive dipping of implant surfaces to polycation and polyanion solutions with intermittent rinsing steps leads to formation of thin fi lms due to the interactions of polyanions and polycations. These fi lms can be further loaded with bioactive agents for their controlled release.…”

Macrophage responses to implants: prospects for personalized medicine

“…2) Polyelectrolyte multilayers are composed of sequentially deposited polyanions and polycations to form thin, ordered, hydrated structures with specific surface properties. These thin coatings can also be loaded with bioactive molecules to act as delivery systems [84,85]. They can be produced with nanoscale precision, up to several tens of micron-thick constructs, and they can conform to any kind of surface topography, making them a good candidate for implant coating.…”