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

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...

Full description

Saved in:
Bibliographic Details
Published inPharmaceutics Vol. 10; no. 1; p. 5
Main Authors Aranda-Barradas, María E, Márquez, Maripaz, Quintanar, Liliana, Santoyo-Salazar, Jaime, Espadas-Álvarez, Armando J, Martínez-Fong, Daniel, García-García, Elizabeth
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 03.01.2018
MDPI
Subjects
formulation
Gene therapy
lyophilization
Nanoparticles
Parkinson's disease
stability
transfection
Transmission electron microscopy
formulation
gene therapy
lyophilization
nanoparticles
stability
transfection
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors contributed equally to this work.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics10010005