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This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G2/M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D7.4, all the synthesized compounds follow Lipinski's rule of five for good permeability (absorption) potential.

Poly(DL-lactide-co-glycolide) (PDLLGA) and poly(L-lactide-co-glycolide) (PLLGA) copolymers were prepared by bulk ring opening polymerization of lactide and glycolide and characterized by GPC, FTIR, 1H NMR and DSC. Copolymers with different molar masses at a constant lactide/glycolide ratio were used for preparation of bovine serum albumin (BSA)-loaded microparticles by the double emulsion w/o/w method. The influence of the copolymer molar mass and composition on the microparticle morphology, size, yield, degradation rate, BSA-loading efficiency and BSA release profile were studied. For microparticles prepared from PDLLGA copolymers, a biphasic profile for BSA release was found and for those made from PLLGA copolymers the release profile was typically triphasic; both of them were characterized by high initial burst release. Possible reasons for such behavior are discussed.

Biodistribution studies of radiolabelled 131I-BSA loaded gelatin microspheres were carried out on BALB/c mice after peroral administration. To two groups, radiolabelled 131I-BSA gelatin microspheres of different particle size, 1.2 +/- 1.1 microm and 7.0 +/- 1.2 microm, were administered orally. To the control group, a solution of 131I-BSA was administered orally as well. Biodistribution was followed periodically within 15 days as the percent of total radioactivity present in the stomach and small intestine with Peyer's patches and mesentery, in colon with Peyer's patches, appendix and mesentery, in liver, spleen, blood, kidney, lungs and heart. Preliminary in vitro biodegradation and drug release studies confirmed the potential of gelatin microspheres to protect the antigen of interest from enzymatic degradation in the gut, and to release it in a controlled manner. The biodistribution data confirmed that particle uptake into Peyer's patches and passage to the liver and spleen via the mesentery lymph supply and nodes increased with decreasing particle size.