Photo-responsive oil core based polymer nanocapsules

The following PhD project regards the field of the drug delivery systems. In particular, the aim of this project is the study of chemical modifications useful to activate photo-stimuli-responsive oil core polymer nanocapsules as theranostic delivery system. Mainly, we will focus the attention on layer by layer (LbL) polymer based nanocapsules loaded with natural drugs and safe contrast agents. In the tumor treatment context, our main purpose is the use of safe nanocarriers to reduce the side effects for the patient, improving the therapy efficacy and the bioavailability of the drugs. So in this PhD project we study systems which can enhance the clinical performance and the cancer detection exploring chemical modifications in the polymeric compositions and/or in the oil core formulations. To this aim we focused the attention on highly versatile nanocapsules built around an oil core and made of completely biocompatible natural polymers employable for therapeutic and diagnostic purposes. Chemical functionalization of nanoemulsions’ shells is studied to engineer a photo-responsive nanocarrier with spatio-temporal control in the release of the drug. In Chapter 2 a LbL O/W cross-linked photo-responsive nanoemulsion, loaded with a natural drug, curcumin, is explained. As just demonstrated in our group, it is possible to functionalize the polymers deposited on the oil core, such as glycol chitosan and heparin, with a thiol moiety and an allylic moiety respectively, and then create a covalent bond between the polymeric shells via a biocompatible photoinitatior free thiol-ene ‘click’ reaction, to improve the nanosystem’s stability. Starting from this strategy to obtain a stable cross-linked LbL systems, we introduced a photolabile chemical linker, based on a modified N-acetyl cysteine-o-nitrobenzyl moiety, between the polymeric materials of LbL. Functionalized the glycol chitosan with this thiol-photo-responsive moiety and the heparin with an allyl one, we were able to perform the cross-linkage and to stabilize our LbL O/W nanoemulsion multilayer shell by the photoinitiator free thiol-ene ‘click’ reaction. Interestingly, the photo-responsive linker gave us the possibility to trigger a controlled destabilization of the nanocarriers to release the drug by single or multi-photon UV light (365 nm or 740 nm). After the chemical modifications of the nanocarriers and its characterizations in terms of stability and conditions of release, we performed biological studies of uptake and cell viability on melanoma cells. In Chapter 3 it is reported a recent published article which is part of this PhD project. It regards an oral delivery application of our nanoemulsions encapsulating nutraceutical drugs, such as curcumin and lycopene and the study of their cardioprotection and anti-inflammatory effects. These properties have been assessed by in vitro tests performed on cardiomyoblasts (H9C2 cells) in presence of doxorubicin. In Chapter 4 we report another possibility concerning the modification of the oil core formulation of the nanoemulsions, using an inorganic compound, in particular cubic iron oxide nanoparticles as contrast agents. We prepared oil-core-PEG shell nanocarriers encapsulating nanocubic iron oxide nanoparticles to study how these systems respond to in vitro photoacoustic and in vitro and in vivo magnetic resonance imaging. Final conclusion and future perspectives are presented and discussed in Chapter 5. Each part of this work can be seen distinctly or in a more general point of view. In this case, we can think to engineer a photo-responsive LbL O/W nanoemulsion co-loaded with natural drugs and safe contrast agents to employ as theranostic nanocapsules.