Liofilizacija lipidno-alginatnih nanočestica s deksametazonom

master's thesis

• Title (english): Freeze-drying of dexamethasone-loaded lipid/alginate nanoparticles
• Author: Vedrana Habuš
• Mentor: Anita Hafner (mentor)
• Committee member: Anita Hafner (predsjednik povjerenstva)
• Committee member: Jasmina Lovrić (član povjerenstva)
• Committee member: Sandra Šupraha Goreta (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2017-04-21, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Nanočestice kao nosači lijekova predstavljaju nove terapijske sustave kojima se može osigurati ciljana/lokalizirana dostava i kontrolirano oslobađanje lijeka, no također nailaze na ograničenja zbog fizičke i kemijske nestabilnosti. Da bi se poboljšala stabilnost suspenzija nanočestica provodi se sušenje. Kao jedna od najučinkovitijih metoda sušenja koloidnih sustava pokazala se liofilizacija. Proces liofilizacije koloidnih terapijskih sustava potrebno je optimirati kako bi se nanočestice zaštitile od stresa tijekom liofilizacije. U tu svrhu koriste se različiti krio/lioprotektori.
Cilj ovog rada bio je ispitati krio/lioprotektivni učinak glukoze i trehaloze (1 – 10 %, m/V) pri liofilizaciji suspenzije lipidno-alginatnih nanočestica s deksametazonom. Kao parametri uspješnosti očuvanja fizičkih svojstava mjereni su veličina, indeks polidisperznosti te zeta-potencijal nanočestica.
Pripremljene su lipidno-alginatne nanočestice s deksametazonom temeljem ionske interakcije lipidne (lecitin i kationski lipid) smjese i alginata. Nanočestice su pripremljene s dva različita tipa lecitina (lecitin S45 i lecitin S100) i s različitim masenim omjerima kationskog lipida i lecitina (od 0,7:50 do 9:50) te su karakterizirane s obzirom na veličinu, polidisperznost i zeta-potencijal. Veličina nanočestica ostala je očuvana nakon liofilizacije u prisustvu trehaloze pri koncentraciji od 10 % (m/V), neovisno o tipu lecitina i masenom omjeru lectina i kationskog lipida. U prisustvu glukoze veličina nanočestica ostala je očuvana samo u slučaju liofilizacije nanočestica pripravljenih s lecitinom S45 pri masenom omjeru lecitina i kationskog lipida od 7:50, i to pri koncentraciji glukoze od 5 i 10 % (m/V). Najbolje očuvanje zeta-potencijala nanočestica postignuto je u slučaju liofilizacije nanočestica pripravljenih s lecitinom S45 i uz dodatak trehaloze kao krio/lioprotektora. Liofilizacija suspenzije nanočestica uz dodatak trehaloze kao krio/lioprotektora rezultirala je lofilizatom koji je zauzimao volumen jednak volumenu suspenzije prije liofilizacije. U slučaju liofilizacije uz dodatak glukoze kao krio/lioprotektora, zabilježen je kolaps strukture liofilizata. Provedena preliminarna ispitivanja upućuju na zaključak da je trehaloza bolji krio/lioprotektor od glukoze u procesu liofilizacije lipidno-alginatnih nanočestica.

Abstract (english)

Nanoparticles as drug carriers can provide targeted/localized delivery and controlled drug release, but also encounter limitations due to physical and chemical instability. To improve the stability of suspension of nanoparticles, drying procedures are carried out. Freeze-drying is one of the most efficient methods of colloidal system drying. The process of freeze-drying of colloidal drug delivery system needs to be optimized in order to protect nanoparticles from stress generated during freezing and drying steps. For this purpose, different cryo/lyoprotectants are used.
The aim of this work was to investigate the cryo/lyoprotective effect of glucose and trehalose (1-10 %, w/V) during freeze-drying of dexamethasone-loaded lipid/alginate nanoparticles suspension. In order to evaluate the effectiveness of selected cryo/lyoprotectants, nanoparticles were characterised in terms of size, polydispersity and zeta-potential before and after the freeze-drying.
Dexamethasone-loaded lipid/alginate nanoparticles were prepared by ionic interaction of lipid (lecithin and cationic lipid) mixture and alginate. Nanoparticles were prepared using two different types of lecithin (lecithin S45 or lecithin S100) and at different cationic lipid-to-lecithin weight ratios (from 0,7:50 to 9:50). Size of nanoparticles remained preserved after freeze-drying in the presence of trehalose at the concentration of 10% (w/V), for both lecithin types and all cationic lipid-to-lecithin weight ratios used. In the presence of glucose, nanoparticles size remained preserved only in the case of freeze-drying of nanoparticles prepared with lecithin S45 at cationic lipid-to-lecithin weight ratio of 7:50, and glucose at the concentration of 5 and 10% (w/V). The best preservation of zeta-potential of nanoparticles was achieved in the case of freeze-drying of nanoparticles prepared with lecithin S45 and with the addition of trehalose as a cryo/lioprotectant. Freeze-drying of suspension of nanoparticles in the presence of trehalose as a cryo/lioprotectant resulted in lyophilisate which occupied a volume equal to the volume of the suspension prior to freeze-drying. In the case of freeze-drying in the presence of glucose as a cryo/lioprotectant, collapse of the lyophilisate structure was observed. Conducted preliminary studies suggested that trehalose was better cryo/lyoprotectant than glucose in the freeze-drying process of dexamethasone-loaded lipid/alginate nanoparticles.

• Keywords: liofilizacija; krioprotektor; lioprotektor; nanočestice; lecitin; alginat; glukoza; trehaloza
• Keywords (english): freeze-drying; cryoprotectant; lyoprotectant; nanoparticles; lecitine; alginate; glucose; trehalose
• Language: croatian
• URN:NBN: urn:nbn:hr:163:340604
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-11-17 16:10:16