Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery.

Elga Bandeira,Maria J Prieto,Maria J Fernandez-Ruocco,Silvia Del Valle Alonso,Débora Ferreira,Hugo C De Castro-Faria-Neto,Ramiro M Perrotta,Miquéias Lopes-Pacheco,Marcelo M Morales,Nadia Chiaramoni,Tatiana Maron-Gutierrez,Patricia R M Rocco

doi:10.3389/fphys.2016.00151

Abstract

Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l-tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases.

Highlights

Respiratory illnesses are a major health issue worldwide
To study the influence of amino acids on polymer formation, we recorded the spectra of samples with and without L-tryptophan, FIGURE 2 | Absorbance at 480 nm corresponding to six polymerized units conjugated effectively and absorbance at 520 nm corresponding to nine polymerized units conjugated effectively
We developed lipopolymeric particles associated with three different amino acids, and showed that amino acid integration has different effects on polymerization, according to the structure and net charge of the amino acid, but does not halt the formation of lipopolymers

Summary

Introduction

Lung infections are the most important single contributor to the overall burden of disease in the world, and more than one billion people have chronic respiratory conditions (Zar and Ferkol, 2014). Liposomes are small biocompatible vesicles with the ability to protect cargo from degradation, favoring controlled delivery. Their similarity to lung surfactant—both are enriched in phospholipids—makes them good candidates for lung delivery strategies (Cipolla et al, 2014). They have the advantages of low cost and large-scale manufacturing and they are relatively easy to associate with nucleic acids

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