Microcarriers offer attractive properties in tissue engineering, namely for bone, cartilage, skin, vascular, central nervous system. Although polyester-based microcarriers have been already proposed for this purpose, their surface properties are not specifically adapted to promote cell adhesion and growth.The main purpose of this study was to prepare microcarriers based on poly(D,L-lactide) acid (PDLLA), poly(L-lactide) acid (PLLA), and to study fibroblast behavior (adhesion, spreading, growth and proliferation) in function of microbead topography and surface chemistry. To improve L-929 fibroblast adhesion, surface of the microcarriers has been modified with polycations: chitosan, poly(2-dimethylamino ethylmethacrylate) (PDMAEMA) or chitosan-g-oligolactide copolymer (chit-g-OLA). These two first polyelectrolytes have been physically adsorbed on the preformed microbeads, while chit-g-OLA copolymer has been anchored to the surface during the manufacturing process of microbead formation. This simple approach 1) bypass the use of an emulsifier (polyvinyl alcohol, PVA); 2) avoid surface "contamination" with PVA molecules limiting a control of the surface characteristics.In vitro study of the growth of mouse fibroblasts on the microbeads showed that both surface topography and chemistry affected cell attachment, spreading and proliferation. Cultivation of L-929 fibroblasts for 7 days resulted in the formation of a 3D cell-scaffold network.

In the study, MCF-7 human breast adenocarcinoma cells were used to study cytotoxicity of novel anticancer nanosized formulations, such as docetaxel-loaded nanoemulsion and liposomal formulation of a lipophilic methotrexate (MTX) prodrug. In vitro study of cytotoxicity was carried out in 2 models, namely using 3D in vitro model based on multicellular tumor spheroids (MTS) and 2D monolayer culture. MTS were generated by tumor cell cultivation within alginate-oligochitosan microcapsules. In the case of the monolayer culture, cell viability was found to be 25, 18 and 12% for the samples containing nanoemulsion at concentrations 20, 300 and 1000 nM of docetaxel, respectively, after 48 hs incubation. For MTS these values were higher, namely 33, 23 and 18%, respectively. Cytotoxicity of liposomal MTX prodrug-based formulation with final concentration of 1, 2, 10, 50, 100 and 1000 nM in both models was also studied. MTX liposomal formulation demonstrated lower cytotoxicity on MTS compared to intact MTX. Moreover, MTS were also more resistant to both liposomal formulation and intact MTX than the monolayer culture. Thus, at 1000 nM MTX in the liposomal form, cell viability in MTS was 1.4-fold higher than that in the monolayer culture. MTS could be proposed as a promising tool to test novel anticancer nanosized formulations in vitro.

No abstract