Lipidne nanočestice u vakcinama za prevenciju COVID-19 zasnovanih na iRNK: pregled materijala i procesa primenjenih tokom razvoja i proizvodnje

  • Ivana Pantelić Univerzitet u Beogradu-Farmaceutski fakultet, Katedra za farmaceutsku tehnologiju i kozmetologiju
  • Tanja Ilić Univerzitet u Beogradu-Farmaceutski fakultet, Katedra za farmaceutsku tehnologiju i kozmetologiju
  • Ines Nikolić Univerzitet u Beogradu-Farmaceutski fakultet, Katedra za farmaceutsku tehnologiju i kozmetologiju
  • Snežana Savić Univerzitet u Beogradu-Farmaceutski fakultet, Katedra za farmaceutsku tehnologiju i kozmetologiju
DOI: https://doi.org/10.5937/arhfarm72-33660
Ključne reči: lipidne nanočestice, jonizujući lipid, PEG-lipid, mikrofluidni sistem, uslovi čuvanja

Sažetak


U susret preporučenoj trećoj dozi, razumevanje tehnološkog napretka koji je doveo do razvoja vakcina na bazi informacione ribonukleinske kiseline (iRNK) od interesa je kako stručne tako i šire javnosti. Iako mnoge kompanije koje stoje iza razvoja ovih vakcina još uvek nisu učinile dostupnim podatke o formulaciji, očigledno je da se dominantno oslanjaju na nanotehnološke platforme slične onoj uspešno primenjenoj za registrovani lek OnpattroTM (INN: patisiran). Zadovoljavajuća inkapsulacija iRNK zahteva prisustvo četiri lipida: jonizujućeg katjonskog lipida, PEGilovanog lipida, neutralnog fosfolipida i holesterola. Zajedno sa ostalim ekscipijensima (puferima, sredstvima za podešavanje toničnosti i krioprotektantima), pažljivo odabrani lipidi omogućavaju obrazovanje lipidnih nanočestica (LNPs) mikrofluidnim ili T-junction tehnikama mešanja velike brzine. Međutim, određena ograničenja u primenjenim protokolima procene stabilnosti vakcina, zajedno sa povećanim oprezom kompanija od kojih se željno očekivalo plasiranje vakcina na tržište, dovelo je do rigoroznih uslova čuvanja: -15° do -25°C ili čak -60° do -80°C. Ipak, pojedine kompanije izveštavaju o zadovoljavajućoj stabilnosti svojih iRNK-LNP vakcina kako na 25°, tako i na 37°C tokom nedelju dana. Dalji formulacioni razvoj će svakako obuhvatiti optimizaciju jonizujućih lipida, naročito u smeru povećanja broja bočnih lanaca i podešavanja pKa vrednosti, te dovesti do pojave tzv. druge generacije iRNK-LNP vakcina za prevenciju COVID-19.

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Objavljeno
2022/02/19
Broj časopisa
Vol. 72 Br. Notebook 1 (2022): Arhiv za farmaciju
Rubrika
Pregledni (Revijalni) rad
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