| Project/Area Number |
15500317
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biomedical engineering/Biological material science
|
|---|
| Research Institution | OKAYAMA UNIVERSITY |
|---|
Principal Investigator |
TADA Hiroko Okayama Univ., Faclt.Engineering, Instructor, 工学部・生物機能工学科, 助手 (60271061)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMADA Hidenori Okayama Univ., Faclt.Engineering, Professor, 工学部・生物機能工学科, 教授 (80037613)
SENO Masaharu Okayama Univ., Grad.Sch.Natr.Sci, Associate Professor, 大学院・自然科学研究科, 助教授 (90243493)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | Drug delivery system / Molecular targetting / Artificial virus / anti-cancer drug / Protein Engineering / タンパク質工学 |
|---|
| Research Abstract |
(1)To show that the hollow nanoparticle composed of the envelope protein of hepatitis B virus (Bio-nano particle) is an efficient delivery vector of pharmaceutical drugs to human liver, a model fluorescent compound (calcein) was enclosed in Bio-nanoparticles and added to the cultures of various cell lines. After 1-day culture, calcein was detected specifically in human hepatoma cells (HepG2) but not in cells derived from other tissues.
(2)The system for measuring the amount of drugs encapsulated in Bio-nanoparticles was established by using calcein as a model, and used to find the optimum conditions of electroporation for encapsulation of calcein.
(3)A mutant bio-nanoparticle with substitutions of 8 cysteine residues (M8 particle) was constructed to increase the efficiency of drug-encapsulation, since these cysteine residues frequently formed false and undesirable intramolecular disulfide bridges that prevent the drug influx into the particles. The amount of calcein encapsulated into the resultant M8 particle was 2.5-fold more than that into wild-type Bio-nanoparticle.
(4)By using the conditions determined in (2), an anti-cancer drug of pacritaxel was encapsulated into the improved version of Bio-nanoparticle (M8 particle) described in (3) and added to the cultures of various cell lines. The anti-cancer drug encapsulated in Bio-nanoiparticles inhibited the growth of HepG2 cells 5-times more efficiently than the drug itself.
Thus, these results showed the usefulness of Bio-nanoparticle as a delivery vector specific to human liver for pharmaceutical drugs.
|
