Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo properties
Nanoparticle (NP) therapeutics have the potential to significantly alter the in vivo biological properties of the pharmaceutically active agents that they carry. Here we describe the development of a polymeric NP, termed M-NP, comprising poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol)...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2015
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| Online Access: | http://hdl.handle.net/1721.1/95482 https://orcid.org/0000-0002-2693-4982 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 |
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| author | Kulak, Nora Pridgen, Eric M. Farokhzad, Omid C. Lippard, Stephen J. Johnstone, Timothy Langer, Robert S |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Kulak, Nora Pridgen, Eric M. Farokhzad, Omid C. Lippard, Stephen J. Johnstone, Timothy Langer, Robert S |
| author_sort | Kulak, Nora |
| collection | MIT |
| description | Nanoparticle (NP) therapeutics have the potential to significantly alter the in vivo biological properties of the pharmaceutically active agents that they carry. Here we describe the development of a polymeric NP, termed M-NP, comprising poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-PEG), stabilized with poly(vinyl alcohol) (PVA), and loaded with a water-soluble platinum(IV) [Pt(IV)] prodrug, mitaplatin. Mitaplatin, c,c,t-[PtCl[subscript 2](NH[subscript 3])[subscript 2](OOCCHCl[subscript 2])[subscript 2]], is a compound designed to release cisplatin, an anticancer drug in widespread clinical use, and the orphan drug dichloroacetate following chemical reduction. An optimized preparation of M-NP by double emulsion and its physical characterization are reported, and the influence of encapsulation on the properties of the platinum agent is evaluated in vivo. Encapsulation increases the circulation time of Pt in the bloodstream of rats. The biodistribution of Pt in mice is also affected by nanoparticle encapsulation, resulting in reduced accumulation in the kidneys. Finally, the efficacy of both free mitaplatin and M-NP, measured by tumor growth inhibition in a mouse xenograft model of triple-negative breast cancer, reveals that controlled release of mitaplatin over time from the nanoparticle treatment produces long-term efficacy comparable to that of free mitaplatin, which might limit toxic side effects. |
| first_indexed | 2024-09-23T15:42:46Z |
| format | Article |
| id | mit-1721.1/95482 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:42:46Z |
| publishDate | 2015 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/954822022-09-29T15:39:02Z Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo properties Kulak, Nora Pridgen, Eric M. Farokhzad, Omid C. Lippard, Stephen J. Johnstone, Timothy Langer, Robert S Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT Farokhzad, Omid C. Johnstone, Timothy Lippard, Stephen J. Langer, Robert Kulak, Nora Pridgen, Eric M. Nanoparticle (NP) therapeutics have the potential to significantly alter the in vivo biological properties of the pharmaceutically active agents that they carry. Here we describe the development of a polymeric NP, termed M-NP, comprising poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-PEG), stabilized with poly(vinyl alcohol) (PVA), and loaded with a water-soluble platinum(IV) [Pt(IV)] prodrug, mitaplatin. Mitaplatin, c,c,t-[PtCl[subscript 2](NH[subscript 3])[subscript 2](OOCCHCl[subscript 2])[subscript 2]], is a compound designed to release cisplatin, an anticancer drug in widespread clinical use, and the orphan drug dichloroacetate following chemical reduction. An optimized preparation of M-NP by double emulsion and its physical characterization are reported, and the influence of encapsulation on the properties of the platinum agent is evaluated in vivo. Encapsulation increases the circulation time of Pt in the bloodstream of rats. The biodistribution of Pt in mice is also affected by nanoparticle encapsulation, resulting in reduced accumulation in the kidneys. Finally, the efficacy of both free mitaplatin and M-NP, measured by tumor growth inhibition in a mouse xenograft model of triple-negative breast cancer, reveals that controlled release of mitaplatin over time from the nanoparticle treatment produces long-term efficacy comparable to that of free mitaplatin, which might limit toxic side effects. National Institutes of Health (U.S.) (Grant 5-U54-CA119349) National Institutes of Health (U.S.) (Grant 5-U54-CA151884) National Institutes of Health (U.S.) (Grant 5-R01-CA034992) National Institutes of Health (U.S.) (MIT-Harvard Center of Cancer Nanotechnology Excellence. Grant 5-U54-CA151884-02) National Institutes of Health (U.S.) (MIT-Harvard Center of Cancer Nanotechnology Excellence. Grant 5-U54-CA151884) German Academic Exchange Service (Research Fellowship) National Institutes of Health (U.S.) (1-S10-RR13886-01) 2015-02-24T16:24:08Z 2015-02-24T16:24:08Z 2013-05 2013-04 Article http://purl.org/eprint/type/JournalArticle 1936-0851 1936-086X http://hdl.handle.net/1721.1/95482 Johnstone, Timothy C., Nora Kulak, Eric M. Pridgen, Omid C. Farokhzad, Robert Langer, and Stephen J. Lippard. “ Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo Properties .” ACS Nano 7, no. 7 (July 23, 2013): 5675–5683. https://orcid.org/0000-0002-2693-4982 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1021/nn401905g ACS Nano Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Kulak, Nora Pridgen, Eric M. Farokhzad, Omid C. Lippard, Stephen J. Johnstone, Timothy Langer, Robert S Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo properties |
| title | Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo properties |
| title_full | Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo properties |
| title_fullStr | Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo properties |
| title_full_unstemmed | Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo properties |
| title_short | Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo properties |
| title_sort | nanoparticle encapsulation of mitaplatin and the effect thereof on in vivo properties |
| url | http://hdl.handle.net/1721.1/95482 https://orcid.org/0000-0002-2693-4982 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 |
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