The aim of this research was to prepare novel block copolymer-surfactant hybrid nanosystems using the triblock copolymer Pluronic 188, along with surfactants of different hydrophilic to lipophilic balance (HLB ratio—which indicates the degree to which a surfactant is hydrophilic or hydrophobic) and thermotropic behavior. The surfactants used were of non-ionic nature, of which Tween 80® and Brij 58® were more hydrophilic, while Span 40® and Span 60® were more hydrophobic. Each surfactant has unique innate thermal properties and an affinity towards Pluronic 188. The nanosystems were formulated through mixing the pluronic with the surfactants at three different ratios, namely 90:10, 80:20, and 50:50, using the thin-film hydration technique and keeping the pluronic concentration constant. The physicochemical characteristics of the prepared nanosystems were evaluated using various light scattering techniques, while their thermotropic behavior was characterized via microDSC and high-resolution ultrasound spectroscopy. Microenvironmental parameters were attained through the use of fluorescence spectroscopy, while the cytotoxicity of the nanocarriers was studied in vitro. The results indicate that the combination of Pluronic 188 with the above surfactants was able to produce hybrid homogeneous nanoparticle populations of adequately small diameters. The different surfactants had a clear effect on physicochemical parameters such as the size, hydrodynamic diameter, and polydispersity index of the final formulation. The mixing of surfactants with the pluronic clearly changed its thermotropic behavior and thermal transition temperature (Tm) and highlighted the specific interactions that occurred between the different materials, as well as the effect of increasing the surfactant concentration on inherent polymer characteristics and behavior. The formulated nanosystems were found to be mostly of minimal toxicity. The obtained results demonstrate that the thin-film hydration method can be used for the formulation of pluronic-surfactant hybrid nanoparticles, which in turn exhibit favorable characteristics in terms of their possible use in drug delivery applications. This investigation can be used as a road map for the selection of an appropriate nanosystem as a novel vehicle for drug delivery.
The medical application of nanotechnology in the field of drug delivery has so far exhibited many efforts in treating simple to extremely complicated and life-threatening human conditions, with multiple products already existing in the market. A plethora of innovative drug delivery carriers, using polymers, surfactants and the combination of the above, have been developed and tested pre-clinically, offering great advantages in terms of targeted drug delivery, low toxicity and immune system activation, cellular biomimicry and enhanced pharmacokinetic properties. Furthermore, such artificial systems can be tailor-made with respect to each therapeutic protocol and disease type falling under the scope of personalized medicine. The simultaneous delivery of multiple therapeutic entities of different nature, such as genes and drugs, can be achieved, while novel technologies can offer systems with multiple modalities often combining therapy with diagnosis. In this review, we present prominent, innovative and state-of-the-art scientific efforts on the applications of surfactant-based, polymer-based, and mixed surfactant-polymer nanoparticle drug formulations intended for use in the medical field and in drug delivery. The materials used, formulation steps, nature, properties, physicochemical characteristics, characterization techniques and pharmacokinetic behavior of those systems, are presented extensively in the length of this work. The material presented is focused on research projects that are currently in the developmental, pre-clinical stage.
Gene therapy is the most promising strategy for treating a number of diseases at their most fundamental, genetic level, and it has a wide range of promising clinical and emerging preclinical uses in both the clinic and the laboratory. Gene therapy systems are composed of three fundamental components, with the delivery platform being responsible for the protection and successful delivery of the incorporated therapeutic nucleic acid sequences. A successful delivery platform is critical in the achievement of a therapeutic outcome, and an effective delivery platform is essential in achieving this. A variety of different gene delivery platforms - vectors - are evaluated in this dissertation in terms of their nature, mechanism of action, potential applications, and safety. Of particular importance is the evaluation of their post-delivery pharmacokinetic and adverse drug-metabolite profiles. The different types of vectors, including viral, non-viral, and alternative vectors, are discussed separately in each chapter, while important issues related to the incorporation of these vectors into clinical practice are discussed as well, including the topics of vector development and manufacturing, as well as the current regulatory landscape and efforts to improve it, and finally their prospects for the immediate future.
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