The Synthesis, Optimization And Characterization Of Camptothecin Functional Microspheres

Camptothecin(CPT) and many of its derivatives are unique potent inhibitor of Topoisomerase I(topo I). The large amount of research and production of CPT is limited by natural resources and low level in Camptotheca acuminata and the process of extraction and separation is time-consuming.A series of Camptothecin molecularly imprinted microspheres were prepared by precipitation polymerization, the impact of every factors on the adsorption properties was studied. The optimum conditions are as follows: Camptothecin as template, α-MAA as functional monomer, EGDMA as cross-linker, AIBN as initiator, the synthetic temperature is under 60℃, methanol /chloroform mixed solvent 30 ml, and the molar ratio of Camptothecin:α-MAA:EGDMA is 1:4:15. Under this synthesis conditions, the adsorption ability of molecularly imprinted microspheres(MIPs) are much higher than the non-imprinted microspheres, MIPs also exhibit higher selective adsorption performance. But during high synthetic temperature, CPT may decompose and cause the inefficient sohxlet extraction.The computer simulation is applied in searching a stable analogue in a high degree of similarity with CPT. Five analogues: H,I,J,K,L,T are found to be applied in molecular imprinting as potential alternative templates. Three different binding sites in CPT analogues between α-MAA are: ① Hydrogen bond in hydroxyl functional ring ② Acyl group in Camptothecin maternal ③ Hydrogen bond in amino group. The interaction and binding models between CPT analogues and functional monomer is analyzed, the order of the complex are as follows : H>I>L>K>J, the order of different binding sites are:(1)>(2)>(3).The results shows α-MAA is a good functional monomer, and analogue H is the most substitute template for Camptothecin.Polylactic acid is a biocompatible material in medical care, it can be a new pharmaceutical formulation applied in CPT drugs to protect its activity and can be synthesized in different particle size in the effective sustained drug release area. PLA-CPT microspheres were prepared by emulsion solvent evaporation method, the impact of various factors in the formation were studied: entrapment efficiency, particle size and distribution of PLA microspheres. The optimum conditions are as follows : the molecular weight of PLA is20,000, the concentration of PLA is 4%, the emulsifier of the external phase is 1% gelatin solution, the emulsifier of the oil phase is 2% span-80, when the drug loading is 12.22%, the volume ratio of the inner and outer water phase is 1:300, the microspheres forms by the stirring speed of 800r·min-1and 4h 500r·min-1. Under this conditions, PLA drug-loaded microspheres shows a good sustained release. PLA drug-loaded microspheres also shows acertain inhibition to Malignant Melanoma cancer cells in the preliminary observation.