Stimuli-Responsive Lyotropic Liquid Crystalline Nanosystems with Incorporated Poly(2-Dimethylamino Ethyl Methacrylate)-b-Poly(Lauryl Methacrylate) Amphiphilic Block Copolymer.

Aleksander Forys,Maria Chountoulesi,Costas Demetzos,Evangelia D. Chrysina,Lukasz Otulakowski,Stergios Pispas,Natassa Pippa,Barbara Trzebicka,Varvara Chrysostomou

doi:10.3390/polym11091400

Abstract

There is an emerging need to evolve the conventional lyotropic liquid crystalline nanoparticles to advanced stimuli-responsive, therapeutic nanosystems with upgraded functionality. Towards this effort, typically used stabilizers, such as Pluronics®, can be combined or replaced by smart, stimuli-responsive block copolymers. The aim of this study is to incorporate the stimuli-responsive amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) as a stabilizer in lipidic liquid crystalline nanoparticles, in order to provide steric stabilization and simultaneous stimuli-responsiveness. The physicochemical and morphological characteristics of the prepared nanosystems were investigated by light scattering techniques, cryogenic-transmission electron microscopy (cryo-TEM), X-ray diffraction (XRD) and fluorescence spectroscopy. The PDMAEMA-b-PLMA, either individually or combined with Poloxamer 407, exhibited different modes of stabilization depending on the lipid used. Due to the protonation ability of PDMAEMA blocks in acidic pH, the nanoparticles exhibited high positive charge, as well as pH-responsive charge conversion, which can be exploited towards pharmaceutical applications. The ionic strength, temperature and serum proteins influenced the physicochemical behavior of the nanoparticles, while the polymer concentration differentiated their morphology; their micropolarity and microfluidity were also evaluated. The proposed liquid crystalline nanosystems can be considered as novel and attractive pH-responsive drug and gene delivery nanocarriers due to their polycationic content.

Highlights

Non-lamellar, lyotropic liquid crystalline nanoparticles, such as cubosomes and hexosomes, are proved to be ideal therapeutic nanosystems, allowing sustained content release and bearing tunable structural characteristics [1,2,3]
Ltd., and glyceryl monooleate (Monomuls® 90-O18) [GMO, 1-(cis-9-octadecenoyl)-rac-glycerol], which was purchased from BASF (Düsseldorf, Germany); both were used without further purification
We tried the lowest required stabilizer ratio, replacing the P407 by PDMAEMA-b-PLMA, in order to investigate the ability of the PDMAEMA-b-PLMA copolymer to act as stabilizing agent

Summary

Introduction

Non-lamellar, lyotropic liquid crystalline nanoparticles, such as cubosomes and hexosomes, are proved to be ideal therapeutic nanosystems, allowing sustained content release and bearing tunable structural characteristics [1,2,3]. They are usually prepared from the lipids glyceryl monooleate (GMO). The ability of endosomal and lysosomal escape is considered to be a crucial advantage for nanosystems towards the achievement of more effective drug and gene delivery exactly to the targeted site into the cell and so higher bioavailability [7,8,9,10,11,12,13]

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Conclusion