Liposome Encapsulated Albumin-Paclitaxel Nanoparticle for Enhanced Antitumor Efficacy

• Published in: Pharmaceutical research 2015-03, Vol.32 (3), p.1002-1016
• Main Authors: Ruttala, Hima Bindu, Ko, Young Tag
• Format: Article
• Language: English
• Subjects: Albumin-Bound Paclitaxel; Albumins - chemistry; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Survival - drug effects; Chemistry, Pharmaceutical; Chemotherapy; Drug delivery systems; Drug Stability; Female; G2 Phase Cell Cycle Checkpoints - drug effects; Half-Life; Humans; Injections, Intravenous; Lipids - chemistry; Liposomes; Male; MCF-7 Cells; Medical Law; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Mice, Inbred BALB C; Nanomedicine; Nanoparticles; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Paclitaxel - pharmacokinetics; Paclitaxel - pharmacology; Particle Size; Pharmaceutical sciences; Pharmacology/Toxicology; Pharmacy; Polyethylene Glycols - chemistry; Proteins; Research Paper; Solubility; Technology, Pharmaceutical - methods; Tissue Distribution; Tumors
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-014-1512-2

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 G 2 /M phase and a higher prevalence of apoptotic subG 1 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.