RESUMO
The purpose of this study is to prepare stimuli-responsive chimeric liposomes (i.e. hybrid polymer-lipid liposomes) containing functional copolymers and conduct aqueous solution studies in order to determine their properties and potential as drug-delivery nanocarriers. Two random copolymers, composed of the hydrophilic, pH and thermo-responsive 2-(dimethyl amino) ethyl methacrylate (DMAEMA) monomer and the hydrophobic stearyl methacrylate (SMA) monomer, were synthesized via free-radical polymerization and molecularly characterized using SEC, FTIR, and 1H-NMR. The synthesis was followed by aqueous solution studies, utilising dynamic light scattering (DLS) in order to determine their stimuli responsive self-assembly properties. The preparation of chimeric liposomes was mediated by thin film deposition and hydration, followed by aqueous solution studies via DLS, ζ-potential and fluorescence spectroscopy. The drug-loading studies include curcumin loading via a thin film deposition and hydration technique, while aqueous solution properties of the drug-loaded chimeric liposomes were determined utilizing DLS, and UV-Vis spectroscopy.
Assuntos
Lipossomos , Micelas , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , PolímerosRESUMO
Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.
Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Lipossomos/administração & dosagem , Nanopartículas/administração & dosagem , Polímeros/química , Pirazóis/administração & dosagem , Apoptose , Proliferação de Células , Glioma/metabolismo , Glioma/patologia , Humanos , Concentração de Íons de Hidrogênio , Lipossomos/química , Nanopartículas/química , Células Tumorais CultivadasRESUMO
The major advance of mixed liposomes (the so-called chimeric systems) is to control the size, structure, and morphology of these nanoassemblies, and therefore, system colloidal properties, with the aid of a large variety of parameters, such as chemical architecture and composition. The goal of this study is to investigate the alterations of the physicochemical and morphological characteristics of chimeric dipalmitoylphosphatidylcholine (DPPC) liposomes, caused by the incorporation of block and gradient copolymers (different macromolecular architecture) with different chemical compositions (different amounts of hydrophobic component). Light scattering techniques were utilized in order to characterize physicochemically and to delineate the fractal morphology of chimeric liposomes. In this study, we also investigated the structural differences between the prepared chimeric liposomes as are visualized by scanning electron microscopy (SEM). It could be concluded that all the chimeric liposomes have regular structure, as SEM images revealed, while their fractal dimensionality was found to be dependent on the macromolecular architecture of the polymeric guest.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Lipossomos/síntese química , Fractais , Interações Hidrofóbicas e Hidrofílicas , Lipossomos/química , Microscopia Eletrônica de Varredura , Nanopartículas/química , Poliaminas/química , Poliésteres/químicaRESUMO
Chimeric or mixed nanosystems belong to the class of advanced therapeutics. Their distinctive characteristic compared with other types of nanoparticles is that they combine two or more different classes of biomaterials. These platforms have created a promising and versatile field of nanomedicine, incorporating materials that are biocompatible, such as lipids, but also functional, such as stimuli-responsive polymers. In the present work, thermoresponsive chimeric nanocarriers composed of l-α-phosphatidylcholine (Egg, Chicken) (EPC) phospholipids and poly(N-isopropylacrylamide)-b-poly(lauryl acrylate) (PNIPAM-b-PLA) block copolymers were designed and developed. Initially, model lipid bilayers with incorporated polymers and drug molecule TRAM-34 were built and studied for their thermodynamics, in order to assess the stability and functionality of the systems. Chimeric nanoparticles of EPC and PNIPAM-b-PLA were then developed and evaluated for their physicochemical properties in different medium conditions, as well as for their morphology. Polymer incorporation led to alterations in the properties and morphology of the nanoparticles, while interactions with serum proteins were absent. TRAM-34 was also incorporated inside the developed nanocarriers, followed by incorporation and release studies, which revealed the functionality of the system in elevated temperature conditions. Finally, in vitro studies on normal cells suggest the biocompatibility of these nanosystems. The proposed platforms are promising for further studies and applications in vitro and in vivo.
Assuntos
Lipossomos , Polímeros , Sistemas de Liberação de Medicamentos , Bicamadas Lipídicas , FosfolipídeosRESUMO
The utilization of liposomes in biomedical applications has greatly benefited the diagnosis and treatment of various diseases. These biomimetic nano-entities have been very useful in the clinical practice as drug delivery systems in their conventional form, comprising lipids as structural components. However, the scientific efforts have recently shifted towards the development of more sophisticated nanotechnological platforms, which apply functional biomaterials, such as stimuli-responsive polymers, in order to aid the drug molecule targeting concept. These nanosystems are defined as chimeric/mixed, because they combine more than one different in nature biomaterials and their development requires intensive study through biophysical and thermodynamic approaches before they may reach in vivo application. Herein, we designed and developed chimeric liposomes, composed of a phospholipid and pH-responsive amphiphilic diblock copolymers and studied their morphology and behavior based on crucial formulation parameters, including biomaterial concentration, dispersion medium pH and polymer composition. Additionally, their interactions with biological components, pH-responsiveness and membrane thermodynamics were assessed. Finally, preliminary in vivo toxicity experiments of the developed nanosystems were carried out, in order to establish a future protocol for full in vivo evaluation. The results have been correlated with the properties of the chimeric nanosystems and highlight the importance of such approaches for designing and developing effective nanocarriers for biomedical applications.