Layer-by-layer assembly for manufacturing local chemotherapy platforms with controlled and sustained drug release to prevent local tumor relapse

Introduction: Layer-by-layer (LbL) assembly is characterized by controlled and prolonged drug release over 3 months compared to electrospinning or solvent casting methods, making it a promising approach for local chemotherapy platforms. The aim of this research was to develop local chemotherapy platforms using different layer-by-layer assembly methods to identify the most efficient drug encapsulation and to achieve the uniform and sustained drug release kinetics.

Methods: The platform developed in this study consists of a polycaprolactone substrate and a multilayer coating produced by LbL assembly. The coating contains the chemotherapeutic drug doxorubicin (DOX), which was stabilized for release by preforming an ionic complex between poly-γ-glutamic acid and DOX, which was then used as a polyanion during LbL assembly. Different LbL assembly methods (by spin or dip), various polycations and the addition of DOX-unloaded polyelectrolyte bilayers were examined. The drug release mechanism was studied in vitro in PBS, mimicking the natural environment of physiological fluids with pH 7.4 at 37 °С. The platforms were also tested for the in vitro antitumor activity of DOX using ovarian cancer cells (SKOV-3).

Results: DOX release from the obtained platforms was sustained for over 6 months with minimal burst kinetics and uniformity, but the drug encapsulation in LbL assembly by spin was tenfold higher. Dip-coated platforms had a coefficient of determination (R²) of 0.84, while spin-coated platforms had an R² of 0.94, when compared to a zero-order drug release model. The in vitro studies showed that the platform has no effect on the antitumor activity of DOX.

Conclusions: This work is encouraging for the development of drug delivery systems as it demonstrates the potential of spin-assisted assembly, offsetting the explosive nature of drug release, and showing its highest stability compared to similar studies.