Objective    To optimize the preparation of nanoparticles encapsulating antisense oligodeoxynucleotides in a-butyleyanoacrylate carrier (ASODN in NP) and investigate their stability.     Methods    ASODN in NP were prepared by interfacial polymerization of butyleyanoacrylate (BCA). The formulation and technology of the prepared NP was optimized by using orthogonal design based on the single-factor experiment. The morphology of NP was examined by transmission electron microscope; The size and size distribution of NP were determined by Malvern laser granularity equipment；The encapsulation efficiency and drug loading were determined by HPLC; The ability of protecting oligodeoxynucleotides from serum was investigated on a 20% polyacrylamide-7 Murea sequencing gel (PAGE).      Results    The nanoparticles in the optimal conditions were of regular spherical surface and discrete. The average size was 97.1 nm

the average encapsulation efficiency and drug loading of  ASODN in NP were 96.7% and 10.1% respectively; The oligonucleotides were more efficiently protected from degradation by nucleases than by oligonucleotides adsorbed into nanospheres.    Conclusion    ASODN in NP has good stability

encapsulation efficiency

drug loading and great potential for ASODN delivery.