title: Turning a water and oil insoluble cisplatin derivative into a nanoparticle formulation for cancer therapy.
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.
authors.affiliation: 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.
authors.forename: Shutao
authors.initials: S
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Miao
authors.affiliation: 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.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Ching-Hsuan M
authors.initials: CH
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Leaf
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D054879:Halogenation; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D008081:Liposomes; D014867:Water; D002945:Cisplatin
keywords: Cisplatin; Inorganic drug; Liposome; Nanoparticle