The aim of this project is the preparation of new mesoporous nanocomposites for the development of drug delivery systems, which ensure the targeted release of antineoplastic and multi-drug resistance-reversal agents. One of the main goals will be obtaining of nanosized mesoporous silicas (MS) (SBA-16, KIT-6 and KIL-2) and nanocomposite mesoporous materials (ZSM-5/SBA-15 and Fe3O4/MS) as well as their modification with suitable functional groups (NH2, SO3H and COOH) allowing the optimization of the loading with drug substances and their selective release in the pathological tissuies. The interaction between the functionalized mesoporous carriers and the drug substances will be studied through quantum-chemical calculations and NMR spectroscopy. Both the initial and the functionalized mesoporous materials will be characterized by advanced physico-chemical methods. The object of this project will be the development of mesoporous silica drug systems loaded with antineoplastic and multi-drug resistance-reversal agents with synthetic (verapamil, tamoxifen, miltefosine) or natural origin (curcumine and quercetin) in order to optimize the pharmacokinetic parameters and bioavailability and toxicology profile as well. In addition to that, surface modification of the mesoporous nanocomposites with suitable polymers for the improvement of the biocompatibility of the carrier, as well as optimization of the biopharmaceutical parameters of the drug systems will be carried out. The formation of a pH sensitive polymer coating which will aid the targeted delivery and controlled release of the drugs is intended. The drug delivery systems will be characterized in detail in respect of the drug loading, the rate and the extent of release and in-vitro tests for bioadhesion, stability and investigation of the pharmacological effects will be performed. The expected results are connected to the development of new drug delivery systems securing the optimization of the local therapy with anti-inflammatories. The subject of the project will contribute to the interdisciplinary development of the young scientists and will open up new perspectives for the continuation of the joint work between the three organizations. The thus developed nanosized mesoporous drug systems will be characterized in detail with regards to the main physico-chemical (size, size distribution, morphology) and biopharmaceutical (effectiveness and capacity of loading with the drug, speed and degree of release, stability) parameters. In addition to that detailed in-vitro tests for the evaluation of the biocompatibility of the carriers and the pharmacological and cytotoxic effects of the model LV loaded in the mesoporous carriers in comparison to the free drug will be carried out.
Тhe successful fulfillment of the project will result in the preparation of new mesoprous nanocomposite drug-delivery systems which will be have high therapeutic effectiveness, significantly lower toxicity and a possibility to overcome the cellular mechanisms of the multiple drug resistance of the tumor tissues, which will lead to the optimization of anti-tumor chemotherapy. The execution of the project involves interdisciplinary investigations, which will contribute towards the deepening of scientific knowledge and the expansion of the practical skills and will aid the professional development of the young scientists. Additionally, work on the project will open perspectives for furthering the cooperation not only between the separate teams in the project, but also with the foreign scientific-research laboratories with which the members of the team have an already established collaboration.