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An in vivo evaluation of amphiphilic, biodegradable peptide copolymers as siRNA delivery agents.
Barrett, Stephanie E; Abrams, Marc T; Burke, Rob; Carr, Brian A; Crocker, Louis S; Garbaccio, Robert M; Howell, Bonnie J; Kemp, Eric A; Kowtoniuk, Robert A; Latham, Andrew H; Leander, Karen R; Leone, Anthony M; Patel, Mihir; Pechenov, Sergey; Pudvah, Nicole T; Riley, Sean; Sepp-Lorenzino, Laura; Walsh, Eileen S; Williams, J Michael; Colletti, Steven L.
Afiliación
  • Barrett SE; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA. Electronic address: stephanie_barrett@merck.com.
  • Abrams MT; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Burke R; Department of Pharmacokinetics & Drug Metabolism RNA, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Carr BA; Department of Pharmacokinetics & Drug Metabolism RNA, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Crocker LS; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Garbaccio RM; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Howell BJ; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Kemp EA; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Kowtoniuk RA; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Latham AH; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Leander KR; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Leone AM; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Patel M; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Pechenov S; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Pudvah NT; Department of Pharmacokinetics & Drug Metabolism RNA, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Riley S; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Sepp-Lorenzino L; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Walsh ES; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Williams JM; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
  • Colletti SL; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.
Int J Pharm ; 466(1-2): 58-67, 2014 May 15.
Article en En | MEDLINE | ID: mdl-24607208
A series of amphiphilic, biodegradable polypeptide copolymers were prepared for the delivery of siRNA (short interfering ribonucleic acid). The molecular weight (or polymer chain length) of the linear polymer was controlled by reaction stoichiometry for the 11.5, 17.2, and 24.6 kDa polypeptides, and the highest molecular weight polypeptide was prepared using a sequential addition method to obtain a polypeptide having a molecular weight of 38.6 kDa. These polymers were used to prepare polymer conjugate systems designed to target and deliver an apolipoprotein B (ApoB) siRNA to hepatocyte cells and to help delineate the effect of polymer molecular weight or polymer chain length on siRNA delivery in vivo. A clear trend in increasing potency was found with increasing molecular weight of the polymers examined (at a constant polymer:siRNA (w/w) ratio), with minimal toxicity found. Furthermore, the biodegradability of these polymer conjugates was examined and demonstrates the potential of these systems as siRNA delivery vectors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ornitina / Apolipoproteínas B / Péptidos / Fenilalanina / Polímeros / ARN Interferente Pequeño Límite: Animals Idioma: En Revista: Int J Pharm Año: 2014 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ornitina / Apolipoproteínas B / Péptidos / Fenilalanina / Polímeros / ARN Interferente Pequeño Límite: Animals Idioma: En Revista: Int J Pharm Año: 2014 Tipo del documento: Article Pais de publicación: Países Bajos