@masterthesis{Wildt, type = {Bachelor Thesis}, author = {Wildt, Viktor}, title = {Formulation of Π-Π Stacking Stabilized Polymeric Micelles Co-loaded with Chemotherapeutics and Corticosteroids}, school = {Hochschule Rhein-Waal}, abstract = {Cancer is a complex and lethal disease, based on uncontrolled and malignant growths. Conventional therapies like radiation therapy, surgery and chemotherapy are used to treat cancer. However, and despite being one of the most employed ones, many chemotherapeutic drugs show several drawbacks, such as. low solubility, side-effects, and low accumulation within the cancerous tissue. Drug delivery systems like polymeric micelles can be employed to overcome these problems. Additionally, due to the heterogeneity of the tumour microenvironment, the consistency of these nano-therapies varies. Which can be traced back to heterogeneity in the efficiency of the enhanced permeability and retention effect. Therefore, corticosteroids are also used in conjunction with chemotherapeutics to increase the nanoparticle accumulation within the cancerous tissue. mPEG-bp(HPMA-Bz) based Π-Π stacking stabilized polymeric micelles have shown great potential for encapsulating paclitaxel, one of the leading anticancer drugs. Furthermore, preliminary studies show potential for co-loading these micelles with corticosteroids like dexamethasone and paclitaxel. Based on these premises, this work focused on exploring the first steps towards the manufacturing process of the ΠΠ stacking mPEG-b-p(HPMA-Bz) based micelles to set up the basis for future clinical transition. This was done by introducing continuous production via microfluidics and increasing the shelf-life via either cold chain or lyophilization. Results showed that microfluidics can reproduce the physicochemical properties and drug retention capabilities of Π-Π stacking polymeric micelles loaded with paclitaxel. Furthermore, the preliminary evaluation pointed that the characteristics of these polymeric micelles might be able to be tuned by increasing the flow rate of the aqueous and organic phase and the polymer concentration. Besides, the cold chain procedure can be used to preserve the micelles with minor changes to the physicochemical properties of the polymeric micelles, when PEG2k (5 wt\%) is added. A framework for further studies on the lyophilization has been established and a mixture of PEG2k and sucrose has been able to reduce the size increase after lyophilization from 10.2-fold to 1.2-fold. Even though it is not optimized, these results set the framework for the manufacturing and storage of Π-Π mPEG-b-p(HPMA-Bz) based polymeric micelles.}, language = {de} }