20.500.12556/DKUM-90591 Razvoj novih večvalentnih polifosfatnih pomožnih snovi za uporabo v formulaciji zdravil na osnovi proteinov diplomsko delo univerzitetnega študijskega programa I. stopnje Developing novel multivalent polyphosphates excipients for formulating protein therapeutics Biološka zdravila so trenutno najhitreje rastoči razred farmacevtskih izdelkov, namenjenih zdravljenju bolezni, kot so demenca, rak in artritis, ki so vse pogostejše v razvitem svetu. Njihova glavna prednost je v tem, da z manjšimi odmerki dosežejo enak učinek kot klasična zdravila in imajo manj nezaželenih stranskih učinkov. Vendar pa je eden največjih izzivov pri bioloških zdravilih agregacija proteinov, kar zmanjšuje kakovost in učinkovitost zdravil ter skrajšuje njihov čas uporabnosti. Prisotnost agregatov lahko povzroči tudi življenjsko nevaren odziv imunskega sistema. V diplomski nalogi smo se osredotočili na razvoj novih večvalentnih polifosfatnih pomožnih snovi, ki bi lahko zmanjšale agregacijo proteinov in izboljšale stabilnost bioloških zdravil. Testirali smo vpliv šestih polifosfatnih spojin, ki spadajo v razred "splošno priznani kot varni" (GRAS), na agregacijo modelnega proteina BSA. Te spojine Natrijev polifosfat (NPP), Adenozin trifosfat (ATP), Natrijev tripolifosfat (TPP), Trinatrijev trimetafosfat (TMP), Natrijev heksametafosfat (HMP) in Natrijev klorid (NaCl) kot kontrolno snov. S pomočjo UV-Vis spektroskopije in nefelometrije smo določili koncentracijsko območje, v katerem te pomožne snovi vplivajo na agregacijo BSA ter primerjali njihov učinek na kinetiko agregacije. V drugem delu smo uporabili bioinformacijske metode za načrtovanje nove skupine potencialnih multivalentnih polifosfatnih molekul, ki bi lahko služile kot pomožne snovi v biofarmacevtskih izdelkih. Rezultati naše študije kažejo, da lahko večje polifosfatne molekule bolj učinkovito preprečijo agregacijo proteinov kot manjše, kar bi lahko zmanjšalo potrebne koncentracije pomožnih snovi. To bi pripomoglo k izboljšanju stabilnosti in varnosti bioloških zdravil, kar je ključnega pomena za nadaljnji razvoj in uporabo teh inovativnih terapij. Biological drugs are currently the fastest-growing class of pharmaceutical products, aimed at treating diseases such as dementia, cancer, and arthritis, which are increasingly common in the developed world. Their main advantage is that they achieve the same effect as traditional drugs with smaller doses and fewer unwanted side effects. However, one of the biggest challenges with biological drugs is protein aggregation, which reduces the quality and effectiveness of the drugs and shortens their shelf life. The presence of aggregates can also cause life-threatening immune responses. This thesis focuses on the development of new multivalent polyphosphate excipients that could reduce protein aggregation and improve the stability of biological drugs. We tested the effect of six polyphosphate compounds, classified as "Generally Recognized as Safe" (GRAS), on the aggregation of the model protein BSA. These compounds include trimethyl phosphate (TMP), adenosine triphosphate (ATP), tripolyphosphate (TPP), trimetaphosphate (TMP), hexametaphosphate (HMP), and sodium chloride (NaCl) as a control substance. Using UV-Vis spectroscopy and nephelometry, we determined the concentration range in which these excipients affect BSA aggregation and compared their effects on the kinetics of aggregation. In the second part of the thesis, we used bioinformatics methods to design a new group of potential multivalent polyphosphate molecules that could serve as excipients in biopharmaceutical products. Our study results indicate that larger polyphosphate molecules can more effectively prevent protein aggregation than smaller ones, potentially reducing the required concentrations of excipients. This could contribute to improving the stability and safety of biological drugs, which is crucial for the further development and use of these innovative therapies. proteini agregacija proteinov biološka zdravila pomožne snovi preprečevanje agregacije proteinov. Proteins protein aggregation biopharmaceuticals excipients and the prevention of protein aggregation. true true false [B. Hlade] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2024-09-10 12:26:54 2025-11-05 14:38:31 2025-12-13 03:07:54 0000-00-00 00:00:00 2025 0 Maribor 0 Maribor 1 spletni vir (1 datoteka PDF (XIII, 43 str.)) 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.015:577.112(043.2) 261092355 UN_Hlade_Brin_2025.pdf UN_Hlade_Brin_2025.pdf 1 2DADB16608144AE365FB0472DE6FC258 e87e4f1afffe244b2ffbfbaa6f1234a5d3746f6b5f086bcc3a51f841f08fc9bc 543daa71-ba4c-11f0-8eea-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=200416 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0