Design, Fabricate and Biocompatibility of Bio-Inspired Capsules as Target Drug Delivery Carriers

A novel encapsulation technology based on layer-by-layer assembly of oppositely charged polyelectrolyte on various colloid templates has been established. With this technology, a variety of polyions including synthetic and natural materials have been used to constitute polyelectrolyte multilayer microcapsules. Thus hollow capsules with tailored functions, such as a catalysts, reaction cages and drug carriers can be prepared. As a model for biological membranes, complex films of protein and lipid have attracted significant interest due to their unique biological properties and specific interactions. The fabrication of the mixed protein and lipid film with the layer-by-layer technique is rarely reported. Such a pair can be considered as a biomimetic system and used to provide the possibility to incorporate membrane specific components like channels and receptors.

The formation of protein and lipid multilayer on melamine formaldehyde (MF) and polystyrene (PS) colloid particles by layer-by-layer (LBL) self-assembly technique were confirmed by electrophoretic mobility and single particle light scattering (SPLS) measurements. Hollow capsules were obtained after subsequently dissolving the template cores. The yields of intact capsules and the stability of protein/lipid capsules were monitored by confocal laser scanning microscopy (CLSM). The thickness and roughness of lipid/protein capsules were determined by single particle light scattering (SPLS) and atomic force microscopy (AFM). Lipid formed bilayer structure with protein which imitated a biological membrane. Circular dichroism (CD) measurements prove that the structure of protein was preserved in this assembly film. The successful absorption of protein and lipid multilayers on ibuprofen crystals as well as the drug release process was dynamically recorded by optical microscopy and UV-spectroscopy. The results reveal that the release rate of ibuprofen from lipid/protein microcapsules is obviously delayed with times increasing with the wall thickness, indicating that the permeability of the microcapsules can be controlled in a straightforward way by varying the number of lipid/protein deposition cycles.

The biocompatibility of one of the most stable types of microcapsules, those composed of poly-(sodium 4-styrene sulfonate) [PSS] and poly-(allylamine hydrocholoride) [PAH], with cells cultured on two dimensional (2D) substrates and in three dimensional (3D) matrices was investigated in this work. Cells were also cultured with four other types of microcapsules, each composed of at least one naturally occurring polyelectrolyte. At microcapsule to cell ratios up to 100:1, it was found that PSS/PAH microcapsules do not affect number of viable cells more substantially than do the other microcapsules investigated. However, differences in number of viable cells were found as a function of microcapsule composition, and our results suggest particular biochemical interactions between cells and internalized microcapsules, rather than mechanical effects, are responsible for these differences. We then investigated the effects of PSS/PAH microcapsules on cells embedded in 3D collagen matrices, which more closely approximate the tumor environments in which microcapsules may be useful drug delivery agents. Matrix structure, cell invasion, and volumetric spheroid growth were investigated, and we show that these microcapsules have a negligible effect on cell invasion and tumor spheroid growth even at high concentration. Taken together, this work suggests that PSS/PAH microcapsules have sufficiently high biocompatibility with at least some cell lines for use as proof of principle drug delivery agents in in vitro studies.