NDLI: Encapsulation of lipophilic kiteplatin Pt(IV) prodrugs in PLGA-PEG micelles

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hoeschele, James D. Gandin, Valentina Natile, Giovanni Margiotta, Nicola Marzano, Cristina Cutrignelli, Annalisa Denora, Nunzio Laquintana, Valentino Savino, Salvatore
Description	Author Affiliation: Margiotta N ( Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy. nicola.margiotta@uniba.it giovanni.natile@uniba.it.); Savino S ( Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy. nicola.margiotta@uniba.it giovanni.natile@uniba.it.); Denora N ( Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy.); Marzano C ( Dipartimento di Scienze del Farmaco, Università di Padova, via Marzolo 5, 35131 Padova, Italy.); Laquintana V ( Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy.); Cutrignelli A ( Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy.); Hoeschele JD ( Department of Chemistry, Eastern Michigan University, Ypsilanti, MI, 48197 USA.); Gandin V ( Dipartimento di Scienze del Farmaco, Università di Padova, via Marzolo 5, 35131 Padova, Italy.); Natile G ( Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy. nicola.margiotta@uniba.it giovanni.natile@uniba.it.)
Abstract	Biodegradable, PEG-coated, nanoparticles (NPs) have gained therapeutic application as injectable colloidal systems for the controlled and site-specific release of drugs. In this paper, encapsulation in PLGA-PEG polymer NPs has been exploited to lower the toxicity and to increase the antitumor activity of kiteplatin $([PtCl_{2}(cis-1,4-DACH)]).$ Kiteplatin contains an isomeric form of the diamine ligand present in oxaliplatin and proved to be particularly active against ovarian and colon cancers. To favor encapsulation of the platinum drug in the hydrophobic core of the polymeric micelles, Pt(IV) prodrugs having hydrophobic carboxylic ligands at the axial positions were used in place of hydrophilic Pt(II) complexes (compounds 1–4). The size, size distribution, and zeta potential (ZP) were measured by dynamic light scattering (DLS) and laser Doppler velocimetry (LDV), and drug encapsulation efficiency (EE) correlated to the alkyl chain length of the different Pt(IV) prodrugs. The number of the Pt atoms per NP (in the range of 1.3–2.4 × $10^{6})$ is comparable to that of polysilsesquioxane-based NPs and higher than that found for other nanoparticle platforms. The platinum-loaded PLGA-PEG NPs, tested in vivo in a syngeneic murine solid tumor (LLC), had a higher antitumor effect and, most importantly, were markedly less toxic than kiteplatin.
ISSN	14779226
Issue Number	33
Journal	Dalton Trans.
Volume Number	45
e-ISSN	13645447
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2016-08-16
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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