Unutarstanično prometovanje čvrstih lipidnih nanočestica

master's thesis

• Title (english): Intracellular trafficking of solid lipid nanoparticles
• Author: Viktorija Herceg
• Mentor: Maja Matulić (mentor)
• Committee member: Maja Matulić (predsjednik povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Committee member: Inga Marijanović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2011-10-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Čvrste lipidne nanočestice (SLN) su koloidalni prenosioci lijekova izgrađeni od biorazgradivih lipida. One poboljšavaju bioraspoloživost molekula slabo topivih u vodi i omogućuju produženo otpuštanje lijeka. SLN punjene edelfosinom, lijekom protiv raka, pokazale su obećavajuće rezultate u životinjskim modelima in vivo. Međutim, mehanizam djelovanja edelfosina ostao je nepoznat. Ciljevi ovoga rada bili su: razjasniti unos i unutarstanično prometovanje SLN fluorescencijskom mikroskopijom i transmisijskom elektronskom mikroskopijom (TEM) te procijeniti djelovanje slobodnog edelfosina i SLN punjenih edelfosinom na stanične linije raka inhibicijom proliferacije i apoptozom. SLN su bile pripremljene vrućom homogenizacijom. Razni fluorescentni spojevi (perilen, DiD, rodamin i Nile Red) bili su uspješno uklopljeni u SLN. Rezultati fluorescencijske mikroskopije i TEM-a pokazali su da su SLN ušle u stanice HL-60, K562 i GS-9L. Otpornost stanica GS-9L na djelovanje slobodnog edelfosina pokazana je inhibicijom proliferacije. SLN punjene edelfosinom djelovale su na stanice GS-9L, dok sam lijek nije pokazao nikakav učinak.

Abstract (english)

Solid lipid nanoparticlers (SLN) are colloidal drug carriers made of biodegradable lipids. They can improve the bioavailability of poorly water-soluble molecules and provide sustained release over time. SLN loaded with the anti-cancer drug edelfosine showed promising results in in vivo xenograft animal models. However, edelfosine mechanism of action remains unknown. The objectives were: to elucidate the uptake and intracellular trafficking of SLN by using fluorescent microscopy and transmission electron microscopy (TEM) and to evaluate the effect of free edelfosine and edelfosine-loaded SLN on cancer cell lines by inhibition of proliferation and apoptosis. SLN were prepared by hot homogenization. Various fluorescent compounds (Perylene, DiD, Rhodamine, Nile Red) were successfully encapsulated in SLN. SLN were uptaken by HL-60, K562 and GS-9L cells as demonstrated by fluorescent and TEM studies. GS-9L cell were resistant to action of free edelfosine as demonstrated by inhibition of proliferation. Edelfosine loaded-SLN were effective in treating GS-9L cell line whereas the free-drug was practically devoid of efficacy.

• Keywords: čvrste lipidne nanočestice; edelfosin; Nile Red; fluorescencijska mikroskopija; transmisijska elektronska mikroskopija; inhibicija proliferacije; apoptoza
• Keywords (english): solid lipid nanoparticles; edelfosine; Nile Red; fluorescence microscopy; transmission electron microscopy; inhibition of proliferation; apoptosis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:051287
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-03 08:29:17