Investigation of Nanocarriers as Drug Delivery Systems by Electron Paramagnetic Resonance Spectroscopy

• Main Author: Saeidpour, Siavash
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2019
• Subjects: Biomedical engineering; Nanotechnology; Pharmaceutical sciences
• ISBN: 9798698513278

In this thesis, the potential of the electron paramagnetic resonance (EPR) spectroscopic technique is applied to questions at the interface of dermatology, pharmacology, chemistry, and nanotechnology.The skin as the outermost part of the body is the only organ to which drugs can be administered directly for the treatment of its diseases. However, the skin also acts as the barrier between the surrounding and the internal organs. Consequently, it protects the whole body against xenobiotics of the external environment. Thereby, the skin prevents penetration of administered drugs into its deeper layers or through it. Overcoming this intrinsic barrier is of great importance in dermatology for therapy success. Nanocarriers as drug delivery systems may be a solution for penetration through the skin barrier and are candidates for drug administration. However, efficient nanocarrier fabrication requires detailed knowledge about the interaction of drugs with these nanocarriers, in particular, with respect to the localization and distribution of the drugs within them. The aim of the study presented here is to unravel such interactions for two specific types of nanocarrier, dendritic core-multishell (CMS) nanoparticles and nanostructured lipid particles (NLP), which are both promising nanocarrier candidates.Since EPR has been established as a useful tool for probing the interaction of a spin probe with its micro-environment, it was chosen here as the method of choice for identifying these interactions. However, EPR requires paramagnetic species, while drugs typically are diamagnetic. Therefore, and in the sense of a pilot study, the small paramagnetic nitroxides 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) and proxyl carboxylic acid (PCA) were used as model compounds for studying their interactions with their environment. The drug Dexamethasone (Dx), used in dermatology for treating inflammatory diseases, was spin labeled with PCA (DxPCA) and utilized for investigating the interactions in both, NLP and CMS nanoparticles. Using a set of continuous wave (cw) and pulsed EPR methods at X- and W-band enabled the precise extraction of the g- and A-matrices of the paramagnetic species as well as the measurement of their relaxation times. The g- and A-matrices represent specific probes for the polarity/proticity of the micro-environment. Additionally, the spin-lattice relaxation time yields complementary data on the spin probes’ micro-environment, which is independently corroborated by the mobility of the spin probes.This EPR-derived information is then used for the localization of the spin probes within the nanocarriers. Finally, comparing all obtained data enabled presenting an "association model" for the interaction between spin probes and nanocarriers. In short, in NLPs DxPCA is dispersed within the entire lipid matrix, PCA is not loaded, and TEMPO is enriched within the core. Likewise, the evidence obtained from EPR shows that DxPCA is localized at the interface between the hydrophobic and the hydrophilic shells of CMS nanoparticles. This knowledge gained may now be used in order to design more efficient nanocarriers or to select the right ones in dependence of the drug to be delivered.