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The search for novel proline analogs for viscosity reduction and stabilization of highly concentrated monoclonal antibody solutionsPrašnikar, Monika ...Administration of monoclonal antibodies (mAbs) is currently focused on subcutaneous injection associated with increased patient adherence and reduced treatment cost, leading to sustainable ... healthcare. The main bottleneck is low volume that can be injected, requiring highly concentrated mAb solutions. The latter results in increased solution viscosity with pronounced mAb aggregation propensity because of intensive protein-protein interactions. Small molecule excipients have been proposed to restrict the protein-protein interactions, contributing to reduced viscosity. The aim of the study was to discover novel compounds that reduce the viscosity of highly concentrated mAb solution. First, the chemical space of proline analogs was explored and 35 compounds were determined. Viscosity measurements revealed that 18 proline analogs reduced the mAb solution viscosity similar to or more than proline. The compounds forming both electrostatic and hydrophobic interactions with mAb reduced the viscosity of the formulation more efficiently without detrimentally effecting mAb physical stability. A correlation between the level of interaction and viscosity-reducing effect was confirmed with molecular dynamic simulations. Structure rigidity of the compounds and aromaticity contributed to their viscosity-reducing effect, dependent on molecule size. The study results highlight the novel proline analogs as an effective approach in viscosity reduction in development of biopharmaceuticals for subcutaneous administration.Vir: International journal of pharmaceutics. - ISSN 0378-5173 (Vol. 655, 2024, 13 str.)Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasleLeto - 2024Jezik - angleškiCOBISS.SI-ID - 191471875
Avtor
Prašnikar, Monika |
Proj, Matic |
Bjelošević Žiberna, Maja |
Lebar, Blaž |
Knez, Benjamin, 1997- |
Osel, Nika, farmacevtka |
Roškar, Robert, 1975- |
Gobec, Stanislav, 1970- |
Grabnar, Iztok |
Žula, Aleš |
Ahlin Grabnar, Pegi
Teme
Farmacevtska kemija |
proline analogs |
monoclonal antibodies |
subcutaneous administration |
viscosity reducers |
high concentration |
prolinovi analogi |
monoklonska protitelesa |
subkutana aplikacija |
sredstva za zmanjševanje viskoznosti |
visoka koncentracija
Avtor | Prašnikar, Monika ... |
Naslov | The search for novel proline analogs for viscosity reduction and stabilization of highly concentrated monoclonal antibody solutions |
Datum objave | 2024-04-25 |
COBISS.SI-ID | 191471875 |
Verzija objave v repozitoriju | Založnikova različica |
Licenca objave v repozitoriju | Creative Commons Priznanje avtorstva 4.0 Mednarodna |
Embargo | Takojšnja javna objava |
Projekti, iz katerih je bila financirana objava
Naziv | Akronim | Številka projekta | Financer |
---|---|---|---|
Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih | P1-0189-2018 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
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Razvoj visokokoncentriranih proteinskih formulacij in vrednotenje kinetike absorpcije po subkutani aplikaciji | L1-3160-2021 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
Datoteke, ki spadajo k objavi
Povezava |
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https://www.sciencedirect.com/science/article/pii/S0378517324002898 |
https://repozitorij.uni-lj.si/IzpisGradiva.php?id=155599 |
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Prašnikar, Monika | 56839 |
Proj, Matic | 52376 |
Bjelošević Žiberna, Maja | 38497 |
Lebar, Blaž | |
Knez, Benjamin, 1997- | |
Osel, Nika, farmacevtka | 53673 |
Roškar, Robert, 1975- | 23549 |
Gobec, Stanislav, 1970- | 15284 |
Grabnar, Iztok | 16107 |
Žula, Aleš | 33054 |
Ahlin Grabnar, Pegi | 15490 |
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