Sinteza votlih sferičnih magnetnih struktur

doktorska disertacija

Marijana Lakić (Author), Aleksandra Lobnik (Mentor), Spomenka Kobe (Thesis defence commission member), Irena Ban (Co-mentor)

Abstract

Rak je eden izmed najpogostejših razlogov smrti sodobnega človeka. Zato so raziskave na področju izboljšav protirakastih zdravilnih učinkovin in novih metod zdravljenja te bolezni, med njimi tudi raziskave na osnovi nanotehnoloških dognanj, v porastu.%Nanomedicina, eno izmed področjih nanotehnologije, hitro raste zahvaljujoč razvoju nanomaterialov ali nano orodij, ki jih lahko uporabimo v namene zgodnjega odkrivanja in zdravljenja bolezenskih stanj ter tkivnega inženirstva. Med temi področji pridobiva tarčna dostava zdravilnih učinkovin na osnovi znanj nanotehnologije in nanomedicine vedno večje zanimanje, saj takšna dostava zdravilnih učinkovin poveča njihovo koncentracijo v tarčnem delu telesa, medtem ko njeno relativno koncentracijo zmanjša v ostalih delih telesa. S tem se izboljša učinkovitost zdravilne učinkovine obenem pa se zmanjšajo njeni stranski učinki. Z raziskavami na tem področju lahko znanstvena stroka bistveno vpliva na število preživelih pacientov, med njimi tudi tistih, obolelih za rakom.%V doktorski disertaciji je prikazana priprava tarčnega sistema za dostavo zdravilnih učinkovin na osnovi votlih sferičnih magnetnih struktur ali votlih magnetnih sfer, ki imajo poleg nanomedicine potencial uporabe še na področju senzorike. Pri tem smo kot osnovo za pripravo tarčnega sistema uporabili mezoporozne delce silicijevega dioksida (SiO2), ki smo jih sintetizirali s pomočjo sol-gel procesa oz. hidrolize in kondenzacije prekurzorja tetraetoksisilana (TEOS) v alkoholnem bazičnem mediju ob prisotnosti površinsko aktivnega sredstva, okoli katerega se je formirala porozna struktura delcev. Pri tem smo spreminjali razne reakcijske parametre in opazovali njihov vpliv na morfološke lastnosti SiO2 delcev, ki smo jih v nadaljevanju oplaščili s pomočjo soobarjanja železovih sulfatnih soli, ki so na površini nosilnih mezoporoznih delcev oksidirale do superparamagnetne maghemitne ovojnice. Proces nastanka votle strukture je potekal simultano s procesom obarjanja železovih soli na površini mezoporoznih SiO2 delcev pri sobni temperaturi z uporabo fosfatnih pufrov. Votle sfere smo tako uspeli pridobiti na okolju prijaznejši in cenovno ugodnejši način, brez uporabe visoko temperaturnih procesov kalcinacije ali okolju spornih topil. Ta postopek smo tudi patentirali. Kemoterapevtska zdravilna učinkovina, ki smo jo uspešno vgradili v takšne votle sfere je doxorubicin (DOX), ki se uporablja pri zdravljenju raznih obolenj, kot so npr. akutna limfoblastična levkemija, rak dojk in jajčnikov, kolorektalni rak ali rak debelega črevesja, rak ledvic, rak jeter, rak glave in vratu, itd. Votle magnetne sferične strukture z vgrajeno zdravilno učinkovino DOX smo uspešno površinsko modificirali z encimom ter ves sistem imobilizirali v biokompatibilni polimerni hidrogel na osnovi vodotopnega polivinil alkohola. Sistem smo okarakterizirali ter podali oceno o primernosti uporabe tega sistema za tarčno dostavo zdravilne učinkovine.

Keywords

nanotehnologija;nanomedicina;votle sfere;mezoporozni delci silicijevega dioksida;doksorubicin;tarčna dostava zdravilnih učinkovin;analizne metode;doktorske disertacije;

Data

Language:	Slovenian
Year of publishing:	2019
Typology:	2.08 - Doctoral Dissertation
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[M. Lakić]
UDC:	620.3:549.514.5(043.3)
COBISS:	22951958
Views:	1090
Downloads:	99
Average score:	0 (0 votes)
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Other data

Secondary language:	English
Secondary title:	Synthesis of hollow spherical magnetic structures
Secondary abstract:	Cancer is one of the most common causes of death in modern society. Studies in the field of improvement of anticancer drugs and new methods of treatment of this disease are on the rise, including the research based on nanotechnology.%Nanomedicine is one of the rapidly growing areas of nanotechnology due to the development of nanomaterials or nanotools, which can be advantageously used for the purposes of tissue engineering and for early detection and treatment of disease states. A rising field of nanomedicine is research of targeted drug delivery. The targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. In other words, the targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. This improves efficacy of the drug while reducing its side effects. Resarch in this field therefore increases the survival of patients.%This doctoral thesis presents the preparation of a targeted drug delivery system for the delivery of active substances on the basis of the hollow spherical magnetic structures or hollow magnetic spheres (HMSs). HMSs have the potential to be used in the fields of nanomedicine and sensing. We used mesoporous silica (SiO2) particles as the templates for the preparation of hollow spheres, which were synthesized via sol-gel process or by the hydrolysis and condensation of tetraethoxysilane (TEOS) precursor in an alcoholic base medium in the presence of a surfactant, which was used as a pore-forming agent. Various reaction parameters were changed, and their effect on the morphological properties of SiO2 particles studied. Porous silica particles were later coated by precipitation of iron salts. Iron salts had oxidized on the mesoporous surface as superparamagnetic maghemite envelopes or external shell. The process of the formation of the hollow interior was conducted simultaneously with the process of precipitation of the iron salts on the surface of mesoporous silica particles at room temperature with the use of phosphate buffers. In this way, we obtained hollow spheres in an environmentally friendly and affordable manner, without the use of high-temperature calcination processes or organic solvents. The described procedure was also patented. Chemotherapeutic active substance Doxorubicin (DOX) was successfully incorporated in such hollow spheres. DOX is used in the treatment of various diseases, such as acute lymphoblastic leukemia, breast cancer, ovarian cancer, colorectal cancer, kidney cancer, liver cancer, head and neck cancer, etc. Hollow spheres with an integrated active ingredient were successfully surface modified by the enzyme and the entire system was protected by biocompatible polymer envelope based on water-soluble polyvinyl alcohol. The system was charactarized and its applicability for targeted delivery evaluated.
Secondary keywords:	nanotechnology;nanomedicine;magnetism;hollow spheres;mesoporous silica particles;doxorubicin;targeted drug delivery;
Type (COBISS):	Doctoral dissertation
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	XIII, 142 str.
ID:	10871255