Development of a Parenteral Formulation of NTS-Polyplex Nanoparticles for Clinical Purpose

Autor: María E. Aranda-Barradas, Maripaz Márquez, Liliana Quintanar, Jaime Santoyo-Salazar, Armando J. Espadas-Álvarez, Daniel Martínez-Fong, Elizabeth García-García
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Pharmaceutics, Vol 10, Iss 1, p 5 (2018)
Druh dokumentu: article
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics10010005
Popis: Neurotensin (NTS)-polyplex is a nanoparticle system for targeted gene delivery that holds great promise for treatment of Parkinson’s disease and various types of cancer. However, the high instability in aqueous suspension of NTS-polyplex nanoparticles is a major limitation for their widespread clinical use. To overcome this obstacle, we developed a clinical formulation and a lyophilization process for NTS-polyplex nanoparticles. The reconstituted samples were compared with fresh preparations by using transmission electron microscopy, dynamic light scattering, electrophoretic mobility, circular dichroism and transfection assays in vitro and in vivo. Our formulation was able to confer lyoprotection and stability to these nanoparticles. In addition, transmission electron microscopy (TEM) and size exclusion-high performance liquid chromatography (SEC-HPLC) using a radioactive tag revealed that the interaction of reconstituted nanoparticles with fetal bovine or human serum did not alter their biophysical features. Furthermore, the formulation and the lyophilization procedure guaranteed functional NTS-polyplex nanoparticles for at least six months of storage at 25 °C and 60% relative humidity. Our results offer a pharmaceutical guide for formulation and long-term storage of NTS-polyplex nanoparticles that could be applied to other polyplexes.
Databáze: Directory of Open Access Journals
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