TY - JOUR
T1 - Development of a parenteral formulation of NTS-polyplex nanoparticles for clinical purpose
AU - Aranda-Barradas, María E.
AU - Márquez, Maripaz
AU - Quintanar, Liliana
AU - Santoyo-Salazar, Jaime
AU - Espadas-Álvarez, Armando J.
AU - Martínez-Fong, Daniel
AU - García-García, Elizabeth
N1 - Publisher Copyright:
© 2018 by the authors.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Formulation
KW - Gene therapy
KW - Lyophilization
KW - Nanoparticles
KW - Stability
KW - Transfection
UR - http://www.scopus.com/inward/record.url?scp=85042136316&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics10010005
DO - 10.3390/pharmaceutics10010005
M3 - Artículo
SN - 1999-4923
VL - 10
JO - Pharmaceutics
JF - Pharmaceutics
IS - 1
M1 - 5
ER -
