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AAPS PharmSciTech

, 20:111 | Cite as

Design, Synthesis, and In Vitro Evaluation of Low Molecular Weight Protamine (LMWP)-Based Amphiphilic Conjugates as Gene Delivery Carriers

  • Sepideh Arabzadeh
  • Zeinab Amiri Tehranizadeh
  • Hamideh Moalemzadeh Haghighi
  • Fahimeh Charbgoo
  • Mohammad RamezaniEmail author
  • Fatemeh SoltaniEmail author
Research Article
First Online:

Abstract

Development of efficient non-viral carriers is one of the major challenges of gene delivery. In the current study, we designed, synthesized, and evaluated the in vitro gene delivery efficiency of novel amphiphilic constructs composed of cholesterol and low molecular weight protamine (LMWP: VSRRRRRRGGRRRR) peptide. Vectors having both hydrophobic and hydrophilic moieties were evaluated in terms of particle size and charge, DNA condensation ability, cytotoxicity, and gene transfection efficiency. The prepared vectors spontaneity self-assembled into the liposome-like particles with a high local positive density. The nano-vehicle A (H5-LMWP-Cholestrol) and nano-vehicle B (LMWP-Cholesterol) could form micelles at concentrations above 50 μg/mL and 65 μg/mL, respectively. The gel retardation assay showed that nano-vehicles A and B could condense pDNA more efficiently than the corresponding unconjugated peptides. The mean of size and zeta potential of complexed nano-vehicle A at N/P ratios of 5, 15, and 30 were 151 nm and 23 mv, and those of nano-vehicle B were 224 nm and 19 mv, respectively. In terms of transfection efficiency, the designed nano-vehicles showed almost two-fold higher gene expression level compared to PEI 25 kDa at optimal N/P ratios, and also exhibited negligible cytotoxicity on a model cancer cell, Neuro 2a. The findings of the present study revealed that these cationic micelles can be promising candidates as non-viral gene delivery vehicles.

KEY WORDS

gene delivery vectors micelles low molecular weight protamine cholesterol 
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Notes

Acknowledgments

This work was supported by Mashhad University of Medical Sciences.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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ESM 1 (JPG 378 kb)
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ESM 2 (JPG 406 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Biotechnology Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
  2. 2.Department of Medicinal Chemistry, School of PharmacyMashhad University of Medical SciencesMashhadIran
  3. 3.Pharmaceutical Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran

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