Treatment of focal cerebral ischemia with liposomal nerve growth factor.
Liposomal nerve growth factor (NGF) was used for the treatment of focal cerebral ischemia in a rat model. Positive charge inducing agents of sphingosine (SP) and stearylamine (S) were formulated in the liposomal NGF. Dose-response of intraventricular injection of liposomal NGF showed significant reduction in infarct volume at the dose of 5 and 10 microg/rat of NGF. The liposomal NGF formulated with SP or S demonstrated similar results in the reduction of total infarct volume in rats. When we increased the molar ratio of SP and S from 0.15 to 0.3, the infarct volume from rats showed a similar value as that of the control treated with NGF solution. Liposomal NGF was given prior to the development of ischemia. We found that NGF was effective in prevention of neuronal death. The NGF concentrations in brain for liposomal NGF were maintained in a level significantly higher than those for NGF solution. This was attributed to the positively charged liposomal NGF bound effectively in brain ventricle and caused longer retention time than free NGF for localization in brain. Therefore, the effect of liposomal NGF on reduction of infarct volume was significant. We assumed that the transportation of NGF might go through the cerebrospinal fluid pathway throughout the ventricular system and subarachnoid system to cerebral cortex to produce a therapeutic effect on ischemia.
Luk
Yun-On
YO
Neurological Institute, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan, ROC.
Chen
Winby York-Kwan
WY
Wong
Wen-Jang
WJ
Hu
Han-Hwa
HH
Hsu
Li-Chi
LC
Chern
Chang-Ming
CM
Huang
Kuo-Jung
KJ
Law
Sai-Lung
SL
D000588:Amines / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001930:Brain Injuries / Q000150:complications*; D002545:Brain Ischemia / Q000150:complications*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002784:Cholesterol / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular / Q000379:methods; D008081:Liposomes / Q000737:chemistry; D008297:Male; D020932:Nerve Growth Factor / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats; D020318:Rats, Long-Evans; D013110:Sphingosine / Q000737:chemistry; D013997:Time Factors; D016896:Treatment Outcome
D000588:Amines; D008081:Liposomes; D010713:Phosphatidylcholines; D020932:Nerve Growth Factor; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine; C009317:stearylamine; D013110:Sphingosine