Synthesis and Nanoprecipitation of HEMA-CLn Based Polymers for the Production of Biodegradable Nanoparticles.

Simone Gatti,Davide Moscatelli,Raffaele Ferrari,Azzurra Agostini

doi:10.3390/polym9090389

Simone Gatti, Davide Moscatelli + Show 2 more

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https://doi.org/10.3390/polym9090389

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Journal: Polymers	Publication Date: Aug 23, 2017
Citations: 9	License type: CC BY 4.0

Affiliation: Politecnico di Milano, ETH Zurich

Abstract

The control over the size distribution and stability of polymeric nanoparticles (NPs) is crucial in many of their applications, especially in the biomedical field. These characteristics are typically influenced by the production method and the nature of the starting material. To investigate these aspects, the controlled radical polymerization of functionalized methacrylates constituted by 2-hydroxyethyl methacrylate (HEMA) functionalized with a controlled number of ε-caprolactone (CL) units (HEMA-CLn), was carried out via reversible addition–fragmentation chain transfer polymerization (RAFT) in solution. The living reaction allows for good control over the molar mass of the final polymer with a low molar mass dispersity. The obtained polymer solutions were nanoprecipitated in order to produce NPs suitable for drug delivery applications with narrow particle size distribution and a wide size range (from 60 to 250 nm). The NP synthesis has been performed using a mixing device, in order to control the parameters involved in the nanoprecipitation process. As already seen for similar systems, the size of the produced NPs is a function of the polymer concentration during the nanoprecipitation process. Nevertheless, when the polymer concentration is kept constant, the NP size is influenced by the chemical structure of the polymer used, in terms of the presence of PEG (poly(ethylene glycol)), the degree of RAFT polymerization, and the length of the caprolactone side chain. These characteristics were also found to influence the stability and degradation properties of the produced NPs.

Highlights

Over the last decades, interest in developing biodegradable polymeric nanoparticles (NPs) as effective drug delivery systems has increased [1,2,3]
The reversible addition–fragmentation chain transfer polymerization (RAFT) polymerization of three ε-caprolactone based macromonomers was investigated, in order to understand the different behavior of polymers in the nanoprecipitation process
For every polymerization a stated value of the [M]0 /[CTA]0 ratio was chosen ([M]0 is the initial concentration of the monomer, [CTA]0 is the initial concentration of the RAFT agent), which corresponded to a target degree of polymerization (DP)

Summary

Introduction

Interest in developing biodegradable polymeric nanoparticles (NPs) as effective drug delivery systems has increased [1,2,3]. The purpose is the creation of a drug vehicle that allows the slow release of the drug (i.e., temporal control) [4], or carries the drug to the site of activity (i.e., distribution control) [5], in order to improve the effectiveness of the drug and to decrease side effects In designing those systems, it is very important to have a good control over the chemical structure of the polymer, and in particular over its molar mass. It is very important to have a good control over the chemical structure of the polymer, and in particular over its molar mass This control allows for a fine tuning of the nanocarrier characteristics, such as dimension, lipophilicity and degradation time [6,7]. These characteristics of the nanocarrier influence the encapsulation efficiency and release profile of encapsulated drugs, the biodistribution of the NPs, their toxicity, and their ability to be efficiently excreted from a living organism.

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