Synthesis, characterization and biological evaluation of new materials for pharmaceutical applications

The work described in this thesis was primarily focused on the synthesis, physicochemical characterization and biological evaluation of new materials for potential pharmaceutical applications. The thesis consists of three parts, each of them related to a different research activity. Part of the work has been dedicated to the study of innovative surfactants, such as sugar esters and biosurfactants produced by Lactobacilli, as attractive alternatives to the commonly employed surfactants. As regards sugar surfactants, a library of different lactose-based monoesters was designed, by employing the disaccharide lactose as polar head group, while varying the fatty acid. Surfactants were fully characterized for their physicochemical properties via nuclear magnetic resonance (NMR), high performance liquid chromatography-mass spectrometry (HPLC-MS), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and surface tension measurements. Antimicrobial activity against different gram-positive and gram-negative bacteria was also investigated, while cytotoxicity and permeability enhancer ability were explored using Caco-2 and Calu-3 cell monolayers. As part of the same project, biosurfactants produced by selected Lactobacillus spp. were also investigated for their surface properties, and anti-biofilm activity against oral Streptococci was finally studied. In the second part, various polymeric materials were synthesized and used in the formulation of drug delivery systems (DDS) intended for the treatment of different diseases. More specifically, N-(2- benzoyloxypropyl) methacrylamide (HPMA-Bz)-based micelles were developed for targeted delivery, by exploiting the cyclic VLA-4 antagonist peptide. Another work carried out in this field, has focused on the formulation and characterization of a Carbopol® hydrogel loaded with methoxy poly(ethylene glycol)-block-poly(lactide-co-glycolide) (mPEG-PLGA) nanoparticles for vaginal delivery with prophilaxis purposes. The topic of the third project described in this thesis is the study of the rheological behaviour of selected polysaccharide dispersions, in function of various physiological parameters, such as concentration, pH and temperature. This rheological analysis provides really useful information, which can potentially help in selecting the polysaccharides with the desired characteristics to be applied in pharmaceutical or nutraceutical formulations.