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Biomaterials. 2014 Aug;35(26):7647-53. doi: 10.1016/j.biomaterials.2014.05.045. Epub 2014 Jun 8.

Turning a water and oil insoluble cisplatin derivative into a nanoparticle formulation for cancer therapy.

Author information

1
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
2
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: leafh@unc.edu.

Abstract

The formulation of water insoluble organic compounds into nanoparticles has become a widely established method for enhancing the delivery and efficacy of cancer therapeutics. Therefore, a comparable approach when applied to water insoluble inorganic compounds should also promote similar advantages. Herein, we have successfully formulated insoluble iodinated cisplatin (CDDP-I) into an LPI NPs (lipid-coated iodinated CDDP nanoparticles). Two separate microemulsions were combined, each containing a precursor for the synthesis of CDDP-I. The resulting CDDP-I precipitate was then coated with an anionic lipid and dispersed in water with the help of an additional lipid. This method allows us to effectively encapsulate CDDP-I and was able to achieve a considerable drug loading of 82 wt%. Administered LPI NPs demonstrated high level accumulation in tumor tissues and exhibited an anti-cancer activity comparable to free CDDP in two melanoma xenograft models without inducing nephrotoxicity. The benefits offered through this delivery formulation are not unique to CDDP-I, as this versatile platform may be extended to the formulation of other inorganic compounds that are both water and oil insoluble into nanoparticles for superior anti-cancer efficacy.

KEYWORDS:

Cisplatin; Inorganic drug; Liposome; Nanoparticle

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