Amphiphilic QP(DMAEMA-co-LMA)-b-POEGMA Random-Block Terpolymers as Nanocarriers for Insulin.

Martha Kafetzi,Xiaoyan Bao,Ping Yao,Stergios Pispas

doi:10.3390/biomedicines8100392

Martha Kafetzi, Xiaoyan Bao + Show 2 more

Open Access

https://doi.org/10.3390/biomedicines8100392

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Abstract

We report on the utilization of the amphiphilic poly[quaternized (2-(N,N-dimethylamino) ethyl methacrylate)]-co-(lauryl methacrylate))-b-poly[(oligo ethylene glycol) methyl ether methacrylate] QP(DMAEMA-co-LMA)-b-POEGMA cationic diblock terpolymer aggregates as nanocarriers for insulin delivery applications. QP(DMAEMA-co-LMA)-b-POEGMA random diblock terpolymer is derived from the chemical modification of the precursor amino diblock copolymer via quaternization, producing permanent positive charges on the macromolecular chain. The QP(DMAEMA-co-LMA)-b-POEGMA diblock terpolymer as well as its amino precursor investigated self-assemble in aqueous media, forming aggregates. In vitro cytotoxicity and in vivo biocompatibility studies on QP(DMAEMA-co-LMA)-b-POEGMA and its amino precursor aggregates, showed good cytocompatibility and biocompatibility. QP(DMAEMA-co-LMA)-b-POEGMA aggregates were chosen to be complexed with insulin due to their self-assembly features and the permanent positive charge in each amino group. QP(DMAEMA-co-LMA)-b-POEGMA aggregates were complexed with insulin through electrostatic interactions. Light scattering techniques were used in order to study the ability of the polymer aggregates to complex with insulin, to determine critical physicochemical parameters such as size, mass, and surface charge of the stable complexes and study the effect of salt addition on their properties. The results showed that in both cases, the complexation process was successful and as the insulin concentration increases, nanosized complexes of different physicochemical characteristics (mass, size, surface charge) and spherical morphology are formed. UV-Vis and fluorescence spectroscopy studies showed that no conformational changes of insulin occurred after the complexation.

Highlights

Over the last few years, protein and gene delivery have attracted significant scientific interest due to their promising application to modern therapeutic and diagnostic technologies to fight life-threatening diseases [1,2]
In vitro cytotoxicity experiments and histological tests have shown that the terpolymer utilized for the formation of complexes is biocompatible and acceptable to be used as an insulin nanocarrier
Mass, and surface charge of the complexes depend on block terpolymer/insulin charge ratio as light scattering techniques indicate

Summary

Introduction

Over the last few years, protein and gene delivery have attracted significant scientific interest due to their promising application to modern therapeutic and diagnostic technologies to fight life-threatening diseases [1,2]. Cancer and diabetes mellitus are severe diseases that threaten a large percentage of the population worldwide [3,4] Traditional medicinal practices, such as chemotherapy and insulin injections, respectively, are implemented to patients who suffer from these diseases. Nanocarriers are synthetic nanostructures that are able to encapsulate pharmaceutical molecules or complex with biomolecules such as DNA/RNA, proteins, liposomes etc., and deliver and release them to target cells without affecting the healthy tissues [6]. Their list of advantages is quite long and as a field that is currently developing, novel properties are still emerging. Nanocarriers combine significant physical and chemical properties that enhance the pharmacokinetics and biodistribution of pharmaceutical/biological molecules since they are capable of distributing the therapeutic substances with greater selectivity and specificity [7]

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