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Pharmaceutics. 2018 Jan 3;10(1). pii: E5. doi: 10.3390/pharmaceutics10010005.

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

Author information

1
Nanosciences and Nanotechnology Department, Center for Research and Advanced Studies of the National Polytechnical Institute, Mexico City 07360, Mexico. mariaaranda500@gmail.com.
2
Chemistry Department, Center for Research and Advanced Studies of the National Polytechnical Institute, Mexico City 07360, Mexico. maripaz.marquez@gmail.com.
3
Pharmacology Department, Center for Research and Advanced Studies of the National Polytechnical Institute, Mexico City 07360, Mexico. maripaz.marquez@gmail.com.
4
Chemistry Department, Center for Research and Advanced Studies of the National Polytechnical Institute, Mexico City 07360, Mexico. lilianaq@cinvestav.mx.
5
Physics Department, Center for Research and Advanced Studies of the National Polytechnical Institute, Mexico City 07360, Mexico. sjimmyster@gmail.com.
6
Physiology, Biophysics and Neurosciences Department, Center for Research and Advanced Studies of the National Polytechnical Institute, Mexico City 07360, Mexico. armandoespadas1@gmail.com.
7
Nanosciences and Nanotechnology Department, Center for Research and Advanced Studies of the National Polytechnical Institute, Mexico City 07360, Mexico. martinez.fong@gmail.com.
8
Physiology, Biophysics and Neurosciences Department, Center for Research and Advanced Studies of the National Polytechnical Institute, Mexico City 07360, Mexico. martinez.fong@gmail.com.
9
Pharmaceutical Nanotechnology Department, Psicofarma, S.A. de C.V., Mexico City 14050, Mexico. elizabeth.garcia@psicofarma.com.mx.

Abstract

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.

KEYWORDS:

formulation; gene therapy; lyophilization; nanoparticles; stability; transfection

Conflict of interest statement

The authors declare that there are no known conflicts of interest associated with this publication and the founding sponsor had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript and in the decision to publish the results.

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