The complexes escape from endosomal compartment enter into cytoplasm and transit through this complex system of microfilaments and microtubules along with highly dense medium of protein and organic molecules that are not only accounted for mechanical resistance but cytoplasmic transport of the organelles as well 55. The cytoskeleton medium composed of various protein and organic molecules has the same viscosity as water, it usually varies with cell type and spatial location 56.
The nucleases present in the cytosol are responsible to reduce the half-life of nucleic acid 57-58. It has been observed that most of the nucleic acids enter into the nuclear envelope during cell division and it must remain stable until the next division of this envelope. Rate of mobility is another important factor in nucleic acid movement through cytoplasm that generally is size and structure dependent.
The rate of mobility of large molecules like DNA fragments sized of 2 kDa have very limited mobility in the cytoplasm and diffuses more than 100 times slowly in cytoplasm compared to water 59. There can be some other aspects that influence the mobility of nucleic acid and prolong trafficking time; including organelles presence in cytoplasm, high protein concentration and the mesh-like structure of cytoskeleton 55. Many studies have shown that the constituents of cytoplasm act as a diffusional barrier for the transportation of pDNA near the nuclear envelope and the majority of injected pDNA remains at its injected site 60. Therefore, the injected site where pDNA released have a great importance for effevtive delivery.