Final Report Summary - STIRENA (Dual stimuli-responsive nanoparticles as novel topical drug delivery systems.)
The STIRENA project focused on the development of novel stimuli-responsive nanoparticles for potential applications as drug delivery systems. The project was organised in three main scientific objectives which focused on the synthesis and characterisation of the nanoparticles, evaluation of their drug uploading and releasing characteristics and studies of their suitability for applications by in vitro toxicity studies and cell internalisation.
The project was successful in obtaining a variety of organic nanoparticles characterised by their ability to release the payload in response to specific stimuli, in particular temperature and pH. There are three main scientific achievements that represent the highlight of the project and each is described here below.
1. The creation of drug loaded nanoparticles of fluorescent PNIPAM nanogels with satisfactory drug loading and entrapment efficiency. PNIPAM nanogels labelled with a fluorescent malemide derivative were obtained by high dilution radical polymerisation. The thermoresponsive property was tailored at 35C by addition of 20% cross-linker. The nanogels were used with neural stem cells and the absence of toxicity was demonstrated with no issues of cell viability up to 70μg/ml, moreover we were able to spot the nanoparticles into the cytoplasm of the cells. Retinoic acid a hydrophobic drug, was successfully loaded without significantly changing the properties of the nanogels. We were able to demonstrate that these nanoparticles do not interfere with the differentiation and self renewal processes of neural stem cells which are their key characteristics. When neural stem cells were treated with drug loaded nanoparticles and are left freely to differentiate, they do not tent to differentiate but keep their neuron identity, which comes as a result of the release of the retinoic acid from the nanoparticles.
2. The creation of self-assembled thermo-responsive nanoparticles of chit-g-PNIPAM in a size of around 30nm. The materials produced were shown to be self-assembled and thermo-responsive. These systems were loaded with retinoic acid, with good drug loading and encapsulation efficiency. The in vitro release profile of the system demonstrates that the release of the model hydrophobic drug is affected both by the temperature as well as the pH. These results allow us to support the idea of the creation of a dual sensitive nanoparticulated drug delivery system able to control the release of the drug while changing the stimulus.
3. The creation of self-assembled thermo-responsive nanoparticles of chit-g-PIPOX with size of 30nm. In this case a new approach and totally new materials were introduced using thermoresponsive polyoxazoline as the grafting polymer on chitosan backbone. Polyoxazolines are characterized by their versatility and their biocompatibility while poly(2-ethyl-2-oxazoline) has already obtained FDA approval. The system created, shows self assembled as well as thermo-responsive characteristics with the size of nanoparticles to be 30nm.
The table here below summarises the list of deliverables and milestones of the project.
D1.1 Synthesis of stimuli responsive POZ-NIPAAM materials ACHIEVED
D1.2 Creation of thermoresponsive POZ-NIPAAM nanogels ACHIEVED
D1.3 Dual stimuli responsive Chitosan-NIPAAM materials ACHIEVED
D1.4 Characterization of stimuli multifunctional materials ACHIEVED
M1.1 Development of Smart Responsive Materials ACHIEVED
D2.1 Study of Unloaded SRN’s ACHIEVED
D2.2 Drug Loaded SRN’s ACHIEVED
D2.3 Characterization of SRN’s ACHIEVED
M2.1 Smart Drug Delivery Systems ACHIEVED
D3.1 Drug-SRN’s in vitro Release Studies ACHIEVED
D3.2 Drug-SRN’s Application in Skin Model ACHIEVED but not on skin model but in neural stem cells
M3.1 Drug-SRN’s Preclinical Evaluation PARTIALLY ACHIEVED