Strategies for development of antimicrobial peptides and proteins

Manteghi Reihaneh
Strategies for development of antimicrobial peptides and proteins.
[Thesis]

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Abstract in foreign language

Many researches have been done with the aim of overcoming AMPs challenges. Different modification strategies as well as different delivery development ideas were offered by these researches. However, peptide modifications and formulation of peptide delivery systems are challenging tasks and hide several risks. Understanding and evaluating the cause - effect relations within the initial Risk Assessment (RA) step in case of all attributes is novelty since it gives the basis for the experimental design as the next step, and aids the formulation development in order to get the final product in the targeted quality range. It also helps to focus on the resources (human, financial, time) related to the final product quality aimed at. By means of RA method within QbD approach of early pharmaceutical development we monitored the factors with highly risk potential in the PEGylation process and risks such as loosing antimicrobial activity of peptide are prevented. The selection of CQAs, CQAs, QTPPs, CQAs and CPPs/CMAs of a PEGylated PGLa formula was performed and interdependence rating among the QTPP elements and CQAs, as well as among the CPPs and CQAs was performed. This careful theoretical study led to the selection of the right methodologies and materials in the synthesis of PEGylated AMPs and their formulation and consequently resulted in obtaining optimized formulation. In our second work, LYZ encapsulated in a novel polyelectrolyte core-shell nanoparticles through the LBL technique utilized as a carrier system to control the release of protein. The preparation of LYZ NPs was made according to 23 full factorial design with QbD approach. Our aim was to understand the effect of process parameters through the determination of mathematical equations, based on which the optimization parameters can be predicted under different process parameters. The optimization parameters were encapsulation efficiency, particle size, enzyme activity, and the amount of α-helix structure. The nanoparticles were analyzed with transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and circular dichroism (CD) spectroscopy. Based on our results, we found that pH was the most important factor and pH 10 was recommended during the formulation. Enzyme activity and α-helix content correlated with each other very well, and particle size and encapsulation efficiency also showed a very good correlation with each other. The results of the α-helix content of FTIR and CD measurements were very similar for the precipitated lysozyme due to the solid-state of lysozyme. The mixing time had the

Item Type: Thesis (Doktori értekezés)
Creators: Manteghi Reihaneh
Divisions: Doctoral School of Pharmaceutical Sciences
Tudományterület / tudományág: Medicine > Pharmacy
Nyelv: English
Item ID: 11284
Date Deposited: 2022. Apr. 28. 11:07
Last Modified: 2022. Apr. 28. 11:07
URI: https://doktori.bibl.u-szeged.hu/id/eprint/11284
Defence/Citable status: Not Defended.

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