Atelocollagen for protein and gene delivery.
Recent progress in recombinant gene technology and cell culture technology has made it possible to use protein and polynucleotides as effective drugs. However, because of their short half-lives in the body and the necessity of delivering to target site, those substances do not always exhibit good potency as expected. Therefore, delivery systems of such drugs are important research subjects in the field of pharmacology, and to prolong the effect of these drugs, many studies are being conducted to control the release of proteins and polynucleotides from various carrier materials. Collagen is one of the most useful carrier materials for this purpose. In this article, we report on the controlled release of protein drugs using collagen, focusing on a new drug delivery system (DDS), the Minipellet, as our basic technology. Then we introduce our recent work about gene therapy using collagen-based DDS. Basic formulation study showed that collagen DDS protects DNA degradation from both chemical cleavage and enzymatic digestion. A single injection of collagen DDS containing plasmid DNA produced physiologically significant levels of gene-encoding proteins in the local site and systemic circulation of animals and resulted in prolonged biological effects. These results suggest that collagen DDS containing plasmid DNA may enhance the clinical potency of plasmid-based gene transfer, facilitating a more effective and long-term use of naked plasmid vectors for gene therapy. Also, variety kinds of application of collagen DDS for gene therapy using adenovirus vector, antisense DNA and DNA vaccine, will be discussed.
Sano
Akihiko
A
Formulation Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., 3-45 Kurakakiuchi 1-choume, Ibaraki, Osaka 567-0878, Japan. sano@sumitomopharm.co.jp
Maeda
Miho
M
Nagahara
Shunji
S
Ochiya
Takahiro
T
Honma
Kimi
K
Itoh
Hiroshi
H
Miyata
Teruo
T
Fujioka
Keiji
K
D020341:Absorbable Implants; D000818:Animals; D003094:Collagen / Q000737:chemistry*; D016373:DNA, Antisense / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage; D010957:Plasmids / Q000008:administration & dosage; D011119:Polynucleotides / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics*; D014176:Protein Biosynthesis; D011506:Proteins / Q000008:administration & dosage* / Q000235:genetics*; D019444:Vaccines, DNA / Q000008:administration & dosage
D016373:DNA, Antisense; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011119:Polynucleotides; D011506:Proteins; D019444:Vaccines, DNA; C059821:atelocollagen; D003094:Collagen