Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice

Figure 1 TEM photography of CTS-Pasp-5Fu nanoparticles showing. It shows the morphological characteristics of CTS-Pasp-5Fu nanoparticles synthesized by ion gelatification. A: The nanoparticles are in regular spherical shape and well distributed; B: The diameter of the particles is between 150-250 nm.

Figure 2 Typical in vitro release profile of pure 5-Fu (▪) and CTS-Pasp-5Fu (▲) in PBS. All pure 5-Fu escaped rapidly from the dialysis bag within the first 1 h. CTS-Pasp-5Fu nanoparticles released 5-Fu gradually up to 100% in 100 h.

Figure 3 The concentration-time curves of 5-Fu group and CTS-Pasp-5Fu nanoparticles group (48 h). The maximal concentration (Cmax) of 5-Fu group occurred within 15 min and decreased rapidly, and that of CTS-Pasp-5Fu nanoparticles group occurred 6 h after the administration and the effective concentration lasted about 14 h.

Figure 4 Tumors in four groups.

Figure 5 Bone marrow cell colonies (≥ 30 nucleated cells constituted one colony) in four groups (× 100). The growth of bone marrow cell colonies in the normal saline group (A), CTS-Pasp group (D) and CTS-Pasp-5Fu group (C) was vigorous, while the cell colonies in the 5-Fu (B) group was sparse. It demonstrated the inhibition effects of 5-Fu used alone. The marrow cell count indicated that CTS-Pasp-5Fu could not suppress the growth of bone marrow cells.

Figure 6 Immunohistochemical atlas of Bcl-2 and Bax expression in four groups (× 200). Bax expression is shown in normal saline group (A), CTS-Pasp group (B), 5-Fu group (C) and CTS-Pasp-5Fu group (D). Bcl-2 expression is shown in normal saline group(E), CTS-Pasp group (F), 5-Fu group (G) and CTS-Pasp-5Fu group (H). The masculine express of Bax in was CTS-Pasp-5Fu group was more obvious than that in the 5-Fu group. CTS-Pasp-5Fu and 5-Fu could up-regulate Bax expression compared with NS. The masculine expression of Bcl-2 in the CTS-Pasp-5Fu group was obviously lower than that in the other three groups. Both CTS-Pasp-5Fu and 5-Fu could both down-regulate the Bcl-2 expression.