Hima Bindu Ruttala1, Young Tag Ko. 1. College of Pharmacy, Gachon University, 191 Hambakmoero Yeonsu-gu, Incheon, 406-799, Republic of Korea.
Abstract
PURPOSE: Albumin nanoparticles have been explored as a promising delivery system for various therapeutic agents. One limitation of such formulations is their poor colloidal stability in vivo. Present study aimed at enhancing the chemotherapeutic potential of paclitaxel by improving the colloidal stability and pharmacokinetic properties of albumin-paclitaxel nanoparticles (APNs) such as Abraxane®. METHODS: This was accomplished by encapsulating the preformed APNs into PEGylated liposomal bilayer by thin-film hydration/extrusion technique. RESULTS: The resulting liposome-encapsulated albumin-paclitaxel hybrid nanoparticles (L-APNs) were nanosized (~200 nm) with uniform spherical dimensions. The successful incorporation of albumin-paclitaxel nanoparticle (NP) in liposome was confirmed by size exclusion chromatography analysis. Such hybrid NP showed an excellent colloidal stability even at 100-fold dilutions, overcoming the critical drawback associated with simple albumin-paclitaxel NP system. L-APNs further showed higher cytotoxic activity towards B16F10 and MCF-7 cells than APN; this effect was characterized by arrest at the G2/M phase and a higher prevalence of apoptotic subG1 cells. Finally, pharmacokinetic and biodistribution studies in tumor mice demonstrated that L-APNs showed a significantly enhanced plasma half-life, and preferential accumulation in the tumor. CONCLUSIONS: Taken together, the data indicate that L-APNs can be promising therapeutic vehicles for enhanced delivery of PTX to tumor sites.
PURPOSE: Albumin nanoparticles have been explored as a promising delivery system for various therapeutic agents. One limitation of such formulations is their poor colloidal stability in vivo. Present study aimed at enhancing the chemotherapeutic potential of paclitaxel by improving the colloidal stability and pharmacokinetic properties of albumin-paclitaxel nanoparticles (APNs) such as Abraxane®. METHODS: This was accomplished by encapsulating the preformed APNs into PEGylated liposomal bilayer by thin-film hydration/extrusion technique. RESULTS: The resulting liposome-encapsulated albumin-paclitaxel hybrid nanoparticles (L-APNs) were nanosized (~200 nm) with uniform spherical dimensions. The successful incorporation of albumin-paclitaxel nanoparticle (NP) in liposome was confirmed by size exclusion chromatography analysis. Such hybrid NP showed an excellent colloidal stability even at 100-fold dilutions, overcoming the critical drawback associated with simple albumin-paclitaxel NP system. L-APNs further showed higher cytotoxic activity towards B16F10 and MCF-7 cells than APN; this effect was characterized by arrest at the G2/M phase and a higher prevalence of apoptotic subG1 cells. Finally, pharmacokinetic and biodistribution studies in tumormice demonstrated that L-APNs showed a significantly enhanced plasma half-life, and preferential accumulation in the tumor. CONCLUSIONS: Taken together, the data indicate that L-APNs can be promising therapeutic vehicles for enhanced delivery of PTX to tumor sites.
Authors: Young Tag Ko; Amit Kale; William C Hartner; Brigitte Papahadjopoulos-Sternberg; Vladimir P Torchilin Journal: J Control Release Date: 2008-10-07 Impact factor: 9.776
Authors: R B Weiss; R C Donehower; P H Wiernik; T Ohnuma; R J Gralla; D L Trump; J R Baker; D A Van Echo; D D Von Hoff; B Leyland-Jones Journal: J Clin Oncol Date: 1990-07 Impact factor: 44.544