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Liposome Encapsulated Albumin-Paclitaxel Nanoparticle for Enhanced Antitumor Efficacy

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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.

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Abbreviations

APNs:

Albumin-paclitaxel nanoparticles

CLSM:

Confocal laser scanning microscopy

DLS:

Dynamic light scattering

DSC:

Differential scanning calorimetry

FACS:

Fluorescence Activated Cell Sorting (Flow Cytometry)

HPLC:

High performance liquid chromatography

L-APNs:

Liposome-encapsulated albumin-paclitaxel hybrid nanoparticles

LC-MS/MS:

Liquid chromatography-tandem mass spectrometry

NP:

Nanoparticle

PTX:

Paclitaxel

XRD:

X-ray diffraction

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ACKNOWLEDGMENTS AND DISCLOSURES

This research was supported by the Basic Science Research Program of Korean National Research Foundation (NRF-20110007794).

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Authors and Affiliations

  1. College of Pharmacy, Gachon University, 191 Hambakmoero Yeonsu-gu, Incheon, 406-799, Republic of Korea

    Hima Bindu Ruttala & Young Tag Ko

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  1. Hima Bindu Ruttala
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  2. Young Tag Ko
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Correspondence to Young Tag Ko.

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Detailed methodology was presented in supplementary file (SM).

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Ruttala, H.B., Ko, Y.T. Liposome Encapsulated Albumin-Paclitaxel Nanoparticle for Enhanced Antitumor Efficacy. Pharm Res 32, 1002–1016 (2015). https://doi.org/10.1007/s11095-014-1512-2

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  • DOI: https://doi.org/10.1007/s11095-014-1512-2

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