Improving bioavailability of insoluble payloads through PLGA nanotechnology

Bioactive molecules are a cluster of natural or synthetic compounds, which modu- late actions in the body promoting good health. Furthermore, they have been ap- plied in the prevention of cancer, heart disease, and other diseases for their antiox- idant, anti-inflammatory, anti-microbial, anti-cancer properties. Among them, many are hydrophobic or poorly soluble nutrients, such as phenolic compounds, ca- rotenoids, essential oils, essential fatty acids, insoluble peptides, and vitamins. Their low water solubility is the limiting factor for their use in both nutraceutical and pharmacological industries. In fact, drugs with poor water solubility show a slower absorption rate, which can lead to inadequate bioavailability making the drug ineffective. Furthermore, hydrophobic molecules can also be used as bio- probe for imaging purpose. Narrow bandwidth emissions and large Stokes shifts make lanthanide complexes interesting as versatile molecular probes of biological systems. Nevertheless, they are not widely used for imaging purpose since their luminescence is completely quenched in aqueous environment. In this scenario, nanoencapsulation through the use of polymeric nanoparticles (NPs ) could be an effective solution to improve solubility and protection of the insoluble payload with consequent increase in bioavailability and action. Poly lac- tic-co-glycolic acid (PLGA) is a synthetic copolymer of lactic acid and glycolic acid of remarkable interest for potential applications in biomedicine; indeed, for its biodegradability and biocompatibility, it has been approved for human use both by Food and Drug Administration (FDA) and European Medicine Agency (EMA). In this thesis, we want to give several proofs of concept about the huge potentiality of PLGA nanoparticles in medical purpose. We used single emulsion methos (O/W) to encapsulate natural bioactive molecules producing planted-derived PLGA nanocarriers enabling anti-inflammatory and antioxidant activity when the polyphe- nol Oxyresveratrol has been incorporated into PLGA NPs. Moreover, an osteogenic promoting action has been observed when PLGA NPs have been embedded with Fisetin (a natural flavonoid).Since PLGA can deliver more than one payload simultaneously, we also produced PLGA nanoassemblies able to combine antibacterial activity with physical treat- ments (such as magnetic and photothermic hyperthermia). Finally, we exploited the shielding properties of PLGA to preserve the luminescence of NIR-emitting lantha- nide complexes in aqueous environment. Therefore, we produced a NIR-CPL probe based on PLGA for bioassay imaging. To summarise, during the past three years we were able to use PLGA encapsulation technology to make natural or synthetic compounds bioavailable, even if naturally water insoluble, and use the loaded nanomaterials in in-vitro experiments assessing the activity of the encapsulated material, paving the way for their application in in- vivo tests and eventual use in nanomedicine.