Multilayered polymeric particle production using superhydrophobic surfaces methodology for drug delivery and tissue engineering applications

Abstract

Encapsulating technologies that render spherical particles containing cells or relevant moleculeshave been developed to be used in fields such as tissue engineering, pharmaceutics, cosmetics, agriculture, as also in other bio-related applications, namely biosensors and bioreactors. The multiple bioactive agents release, with an important role in tissue regeneration, constitutes an important strategy in tissue engineering. The control of bioactive agents release may be achieved increasing the complexity of the encapsulating particles by adjusting the chemistry and the architecture. In this context, multi-compartmentalized systems able to simultaneously deliver various bioactive agents at different kinetics have emerged and are envisioned to be the next area of development. Multilayered particles exhibiting predefined diameters and layers thickness may offer additional advantages including higher bioactive agents loads, improved molecules stability, and tailored release schedules such as delayed or pulsatile avoiding initial bursts. The most external layers could even act as rate-limiting barriers to further reduce burst release. Since multilayered particles are compartmented, each particle can load multiple bioactive agents isolated from each other. Similarly, more than one type of cells may be immobilized into different compartments. The layers thickness and composition determine the performance of the system. Compared to monocompartment delivery systems, the development of multi-compartmented structures is still immature and intensive efforts are being done to efficiently produce this type of systems. The production of multi-compartmented particles is quite challenging and the existing methodologies involve wet and aggressive conditions that compromise the encapsulation efficiency of bioactive agents and the viability of cells. Herein we report a simple bottom-up approach suitable for preparing multilayered polymeric particles in a very fast way, which involves the use of biomimetic superhydrophobic surfaces. In the present work, concentric multilayered polymeric particles were prepared by adding layers one-by-one, and then their applications as carriers for sequential multiple drug release and as scaffolds for cells immobilization intended in cell therapies or tissue engineering were explored. The results showed that the engineered particles can be loaded with different molecules confined in different compartments for later sequential and time-programmed release. They can also immobilize cells maintaining them viable for long time, being potentially useful for cell-based therapies.