Development of Novel EE/Alginate Polyelectrolyte Complex Nanoparticles for Lysozyme Delivery: Physicochemical Properties and In Vitro Safety.

Sabrina Sepúlveda-Rivas,Javier Morales,Carlos Santiviago,Hans Fritz,Camila Valenzuela

doi:10.3390/pharmaceutics11030103

Sabrina Sepúlveda-Rivas, Javier Morales + Show 3 more

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https://doi.org/10.3390/pharmaceutics11030103

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Abstract

The number of biologic drugs has increased in the pharmaceutical industry due to their high therapeutic efficacy and selectivity. As such, safe and biocompatible delivery systems to improve their stability and efficacy are needed. Here, we developed novel cationic polymethacrylate-alginate (EE-alginate) pNPs for the biologic drug model lysozyme (Lys). The impact of variables such as total charge and charge ratios over nanoparticle physicochemical properties as well as their influence over in vitro safety (viability/proliferation and cell morphology) on HeLa cells was investigated. Our results showed that electrostatic interactions between the EE-alginate and lysozyme led to the formation of EE/alginate Lys pNPs with reproducible size, high stability due to their controllable zeta potential, a high association efficiency, and an in vitro sustained Lys release. Selected formulations remained stable for up to one month and Fourier transform-Infrared (FT-IR) showed that the functional groups of different polymers remain identifiable in combined systems, suggesting that Lys secondary structure is retained after pNP synthesis. EE-alginate Lys pNPs at low concentrations are biocompatible, while at high concentrations, they show cytotoxic for HeLa cells, and this effect was found to be dose-dependent. This study highlights the potential of the EE-alginate, a novel polyelectrolyte complex nanoparticle, as an effective and viable nanocarrier for future drug delivery applications.

Highlights

In recent years, the number of proteins and peptide-like drugs in the pharmaceutical industry has increased due to significant therapeutic efficacy and remarkable selectivity, high specificity, activity, minimal drug–drug interactions, and toxicity [1,2]
Our results show that cell viability is higher than 90% after exposure to Eudragit E (EE)/alginate nanoparticles for 24 h
We demonstrated that the decrease in cell viability of HeLa cells treated with EE/alginate nanoparticles was dose-dependent, as the treatment with higher concentrations (1.0 and 1.5 μM) of EE/alginate pNPs inhibited the proliferation HeLa cells ranging from 67.7% to 8.3% (Figure 6)

Summary

Introduction

The number of proteins and peptide-like drugs in the pharmaceutical industry has increased due to significant therapeutic efficacy and remarkable selectivity, high specificity, activity, minimal drug–drug interactions, and toxicity [1,2]. These new classes of protein-based drugs are generally referred to as ‘biologics’ and include molecules such as insulin, growth factors, and engineered antibodies [3]. This has led researchers to accelerate the development of novel delivery systems [1,2] that can maintain the structure, biological activity, and viability of biologics, and that are non-immunogenic, can release the therapeutic agent predictably over time and erode to metabolites that are either absorbed or excreted [9]

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