alexa Biodegradable nanoparticles containing doxorubicin-PLGA conjugate for sustained release.
Materials Science

Materials Science

Journal of Nanomedicine & Nanotechnology

Author(s): Yoo HS, Oh JE, Lee KH, Park TG

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Abstract PURPOSE: Doxorubicin was chemically conjugated to a terminal end group of poly(D,L-lactic-co-glycolic acid) [PLGA] and the doxorubicin-PLGA conjugate was formulated into nanoparticles to sustain the release of doxorubicin. METHODS: A hydroxyl terminal group of PLGA was activated by p-nitrophenyl chloroformate and reacted with a primary amine group of doxorubicin for conjugation. The conjugates were fabricated into ca. 300 nm size nanoparticles by a spontaneous emulsion-solvent diffusion method. The amount of released doxorubicin and its PLGA oligomer conjugates was quantitated as a function of time. The cytotoxicity of the released species was determined using a HepG2 cell line. RESULTS: Loading efficiency and loading percentage of doxorubicin-PLGA conjugate within the nanoparticles were 96.6\% and 3.45 (w/w) \%, respectively while those for unconjugated doxorubicin were 6.7\% and 0.26 (w/w) \%, respectively. Both formulation parameters increased dramatically due to the hydrophobically modified doxorubicin by the conjugation of PLGA. The nanoparticles consisting of the conjugate exhibited sustained release over 25 days, whereas those containing unconjugated free doxorubicin showed rapid doxorubicin release in 5 days. A mixture of doxorubicin and its PLGA oligomer conjugates released from the nanoparticles had comparable IC50 value in a HepG2 cell line compared to that of free doxorubicin. Sustained drug release was attributed to the chemical degradation of conjugated PLGA backbone, which permitted water solubilization and subsequent release of doxorubicin conjugated PLGA oligomers into the medium. CONCLUSIONS: The conjugation approach of doxorubicin to PLGA was potentially useful for nanoparticle formulations that require high drug loading and sustained release. The doxorubicin-PLGA oligomer conjugate released in the medium demonstrated a slightly lower cytotoxic activity than free doxorubicin in a HepG2 cell line.
This article was published in Pharm Res and referenced in Journal of Nanomedicine & Nanotechnology

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