Potencijali i izazovi u razvoju multivezikularnih liposoma

postgraduate specialist thesis

• Author: Maja Radiković
• Mentor: Željka Vanić (mentor)
• Committee member: Zora Rukavina (predsjednik povjerenstva)
• Committee member: Željka Vanić (član povjerenstva)
• Committee member: Renata Jurišić Grubešić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2024-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

CILJ ISTRAŽIVANJA
Cilj ovog rada bio je pružiti sistematizirani pregled objavljene znanstvene i stručne literature vezane za
razvoj i proizvodnju formulacija lijekova temeljenih na tehnologiji multivezikularnih liposoma. Opisana
su specifična strukturna svojstva multivezikularnih liposoma i definirani kritični elementi u proizvodnji
stabilnih formulacija lijekova. Prikazane su prednosti i ograničenja formulacija lijekova
multivezikularnih liposoma u odnosu na konvencionalne oblike liječenja te u odnosu na druge tipove
liposoma.
MATERIJALI/ISPITANICI I METODE
Istraživanje je provedeno pretraživanjem akreditiranih baza podataka prema tematici relevantnoj za
izradu specijalističkog rada. Među općim i specijaliziranim znanstvenim i stručnim člancima odabrani
su relevantni članci s obzirom na postavljene ciljeve te su detaljno proučeni kako bi se napravio
sistematizirani i kritički osvrt na zadanu temu.
REZULTATI
Formulacije multivezikularnih liposoma razvijaju se kako bi se premostila ograničenja konvencionalnih
formulacija lijekova i osigurala dostatna stabilnost lijekova peptidnog karaktera. Zahvaljujući veličini
multivezikularnih liposoma od nekoliko desetaka mikrometara te unutarnjoj strukturi koja podsjeća na
pjenu, nakon primjene formulacije lijeka, moguće je formiranje depoa i produljeno oslobađanje
djelatne tvari kroz dulji vremenski period.
Utvrđeno je da je, uz uobičajene sastavnice liposoma, za formiranje multivezikularnih liposoma
potreban dodatak neutralnih lipida. Korištena metoda pripreme dvostruke emulzije uspješno je
prenesena iz laboratorijskog u industrijsko mjerilo.
Dosad su odobrenje za stavljanje u promet dobile tri formulacije lijekova temeljenih na tehnologiji
multivezikularnih liposoma. Jedna formulacija je dobila odobrenje za kliničko ispitivanje, dok je za
drugu upućen zahtjev za kliničko ispitivanje. Brojne formulacije lijekova u fazi su pretkliničkih
ispitivanja. Dvije odobrene formulacije lijekova povučene su zbog poteškoća u proizvodnji.
ZAKLJUČAK
Lijekovi temeljeni na formulacijama multivezikularnih liposoma pružaju potencijalnu platformu za
premošćivanje brojnih zdravstvenih izazova poput dostave peptidnih lijekova ili dostave lijekova čije
djelovanje ovisi o specifičnoj fazi staničnog ciklusa. Njihova primjena bi mogla pridonijeti poboljšanoj
adherenciji bolesnika zbog smanjene učestalosti doziranja parenteralnih lijekova. Zbog nedostatka
prikladnijih metoda sterilizacije, specifičnog regulatornog okvira i standardiziranih analitičkih metoda,
komercijalizacija ovih lijekova je otežana.

Abstract (english)

OBJECTIVES
The goal of this thesis was to present a systematic review of the published literature on the
development and manufacture of drug formulations based on multivesicular liposome technology.
Specific structural properties of multivesicular liposomes were described as well as critical parameters
in their manufacturing process. The potentials and limitations of drug-loaded multivesicular liposomes
compared to conventional therapy and other types of liposomes were highlighted.
MATERIAL/PATIENTS AND METHODS
The research was conducted by searching accredited databases with regard to the topic of this thesis.
Relevant articles were selected based on the set objectives and studied in detail in order to create a
systematic and critical review of the given topic.
RESULTS
The formulations of multivesicular liposomes are being developed to overcome the limitations of
conventional drug formulations and to ensure adequate stability of peptide-based drugs. Formation of
a depot and prolonged drug release over extended period of time, following administration of drugloaded multivesicular liposomes, are enabled by their size and internal foam-like structure.
The addition of neutral lipids was found to be crucial in formation of multivesicular liposomes. The
implemented double-emulsion method was successfully commercialized.
Until now, three medicinal products based on multivesicular liposome technology were granted
marketing authorisation. One formulation received approval for clinical testing, while a request for
clinical testing has been initiated for another formulation. Numerous drug product formulations are in
the phase of preclinical trials. Two marketed medicinal products have been withdrawn due to
difficulties in the manufacturing process.
CONCLUSION
Drug product formulations based on multivesicular liposome technology provide a potential platform
for overcoming numerous therapeutic challenges like the delivery of peptide drugs or drugs whose
action depends on a specific cell-cycle phase. Utilization of this technology could contribute to
enhanced patient adherence due to the reduction of parenteral administration frequency.
Commercialization of these drug products is difficult due to the lack of adequate sterilization methods,
a specific regulatory framework and standardized analytical methods.

• Keywords: multivezikularni liposomi; formulacije lijekova
• Keywords (english): multivesicular liposomes; drug formulations
• Language: croatian
• URN:NBN: urn:nbn:hr:163:737519
• Study programme: Title: Drug development - specialistic study - university study; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni specijalist razvoja lijekova (sveučilišni specijalist razvoja lijekova)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-02-07 12:44:33