Flexible Liposomes Of Nerve Growth Factor And Its Brain Targeting Of The Preliminary Study

Nerve growth factor (NGF) belongs to the kind of classic molecular peptide which is produced by nerve and target cell managed by nerve . The essay tried to institute the delivery system of peptide according to NGF. The NGF can promote the cell to grow , divide and survive, and also can cure nerve system disease. NGF is ready to lose biological activity quickly in water solution and is sensitive to many conditions such as pH,high temperature, and so on. The use of NGF is limited ,as it can't cross the BBB freely .In my experiment I try to change dosage in order to solve the question of stability and attempt to elevate the penetration of the BBB.First,establish the analytic method of peptide by quenching of scattering light of silver chloride gel .Then, select the IL-2 as model drug and prepare liposome suspension . Establish the analynatic method of encapsulation efficiency(EE) through DEAE-sephadex A50 minicolumn centrifuge;Select the EE as the parameter and make the single factor experiment . Based on the single factor experiment , the optimal formulation is obtained by orthogonal design test. With the optimal formulation ,the EE of the liposome is 33.11%. Use the 0.22 μm micropore sterilization on account of the specific nature of the NGF. In order to enhance the NGF's stability , prepare the lyophilized liposome . Select the optimal lyophilized formulation according to EE, appearance,rehydration .Discuss the physical and chemical stability of the NGF liposome suspension and lyophilized liposome. Under high temperature or intense light, the liposome suspension and lyophilized liposome both have feeble stability , but the lyophilized liposome is stronger than the liposome suspension.The accelerated stabilitv experiment indicates the shelf life of lyonhilized linosome is about twoyears. On the basis of physical and chemical character , discuss the biological stability by means of outgrowth of chicken embryo dorsal ganglia. The result of experiment indicate the lyophilized liposome can maintain the biological activity for three months under 4 ℃.The physical and chemical properties of lyophilized liposome weredescribed.Transmission election microscopy and the Laser scattering mersurementshowed that NGF particle was nanoparticle with mean diameter of 39.6 nm. The, experiment showed that NGF lyophilized liposome was positive whichenhance the NGF penetration of the BBB.The safety experiments of rehydrated liposome such as vessel irritation and hemolysis ,were tested for intravenous administration. It was showed that lyophilized liposome was safe formulation and nonirritant.The preliminary studies of pharmacokinetics were evaluated in mouses. The plasma NGF concenteation was determined by labeling with99Tc with the SDS-PAGE and SPECT .The pharmacokinetic characteristics of rehydrated lyophilized liposome conformed two compartments model.The preliminary studies of brain tissue distribution were determined by SPECT .