Stability and bioactivity of nanocomplex of TNF-related apoptosis-inducing ligand.
The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has gained much attention due to its potent therapeutic effect for cancer and rheumatoid arthritis. In this study, we attempted to develop the injectable formulations which can stabilize TRAIL and thus show prolonged blood circulation in vivo. The positively charged TRAIL was mixed with hyaluronic acid (HA), resulting in the formation of nanocomplexes. The zeta-potentials of nanocomplexes and their mean diameters were significantly dependent on the feed ratio of HA to TRAIL. The increase in the feed ratio of HA reduced the particle size and decreased the value of the zeta-potential. The bioactivity of TRAIL in the complexes was comparable to that of native TRAIL, indicating that the complex formation did not affect the activity of TRAIL. Furthermore, the stability of TRAIL in the complexes was retained for 6 days, during which the bioactivity of native TRAIL disappeared. When native TRAIL was subcutaneously injected into the rats, its plasma concentration was not detectable after 12h. In contrast, for HA/TRAIL nanocomplexes in 1% HA solution, substantial amount of TRAIL was circulated in blood for up to 5 days. These results imply that HA-based formulations of TRAIL hold the potential as the therapeutics.
Na
Seong Ju
SJ
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
Chae
Su Young
SY
Lee
Seulki
S
Park
Kyeongsoon
K
Kim
Kwangmeyung
K
Park
Jae Hyung
JH
Kwon
Ick Chan
IC
Jeong
Seo Young
SY
Lee
Kang Choon
KC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006367:HeLa Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007279:Injections, Subcutaneous; D008297:Male; D053758:Nanoparticles; D055550:Protein Stability; D051381:Rats; D017207:Rats, Sprague-Dawley; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D004337:Drug Carriers; D053221:TNF-Related Apoptosis-Inducing Ligand; D006820:Hyaluronic Acid