Title Kompozitne mikročestice kao sustavi za dostavu lijeka Title (english) Composite microparticles as drug delivery systems Author Martina Omazić Mentor Anamarija Rogina (mentor)Committee member Anamarija Rogina (predsjednik povjerenstva)Committee member Marica Ivanković (član povjerenstva)Committee member Leonard Bauer (član povjerenstva)Granter University of Zagreb Defense date and country 2024-02-23, Croatia Scientific / art field, NATURAL SCIENCES Abstract Cilj ovoga rada bila je priprema kompozitnih kitozan-bakar(II)/hidroksiapatit mikročestica te ispitivanje mogućnosti inkapsulacije antitumorskog lijeka u pripremljene materijale u svrhu priprave sustava za ciljanu dostavu lijekova. Kitozan (CHT), kao jedan od najvažnijih poliaminosaharida, izazvao je veliki interes zbog svojih poželjnih svojstava i široke primjene. Kitozan ima sposobnost stvaranja stabilnih kelata s bioaktivnim metalnim ionima, te je u ovom radu pripremljena polimerna matrica na temelju kitozan-Cu2+ kompleksa. S ciljem povećanja efikasnosti ugradnje antitumorskoga lijeka u matricu, pripravljene su kompozitne mikročestice dodatkom anorganskog punila (hidroksiapatit, HAp). Metoda elektroštrcanja je korištena za proizvodnju visoko sferičnih mikronosača na temelju kompozita CHT-Cu/HAp zbog svoje jednostavnosti i visoke efikasnosti. Za identifikaciju dobivenih mikročestica korištene su infracrvena spektroskopija s Fourierovom transformacijom prigušene totalne refleksije
(ATR-FTIR) i rendgenska difrakcijska analiza (XRD). Oblik, veličina i raspodjela veličina mikročestica određeni su pomoću pretražnog fluorescentnog mikroskopa. Stupanj bubrenja mikročestica određen je u otopinama fosfatnog pufera pH vrijednosti 6 (PB-6) i 7,4 (PB-7,4) te u demineraliziranoj vodi (H2O, pH 6,5). Ugradnja antitumorskoga lijeka (doksorubicin, DOX) provedena je u blago kiselom mediju tijekom jednog, odnosno tri sata, pri 37 °C te su svojstva mikročestica s ugrađenim lijekom ispitana primjenom pretražnog fluorescentnog mikroskopa, fluorescentne spektrometrije i gravimetrijske metode. XRD i FTIR analize pokazale su prisutnost hidroksiapatita u pripravljenom CHT-Cu/HAp kompozitu, te su mikročestice dobivene procesom elektroštrcanja bile sferičnoga oblika uz prosječnu veličinu čestica 56,1 ± 5,1 μm za CHT-Cu sustav, odnosno 72,1 ± 17,6 μm za CHT-Cu/HAp sustav. Ispitivanje stupanja bubrenja pokazalo je da mikročestice najviše bubre u kiselom mediju te da se s dodatkom hidroksiapatita povećava stupanj bubrenja. Primjenom fluorescentne mikroskopije utvrđena je uspješna ugradnja doksorubicina u CHT-Cu i CHT-Cu/HAp mikročestice. Rezultati fluorescentne spektrometrije i gravimetrijske metode ukazali su na prisutnosti soli fosfata u mikročesticama. Dobiveni rezultati pokazali su da pripravljene kompozitne mikročestice mogu poslužiti kao potencijalni sustavi za dostavu lijeka.
Abstract (english) This work aimed to prepare composite chitosan-copper/hydroxyapatite microparticles and investigate the possibility of loading an antitumor drug, forming a targeted drug delivery system. Chitosan (CHT), one of the most important polyaminosaccharides, has drawn attention due to its desirable properties and wide applications. Chitosan can form stable chelates with bioactive metal ions, and in this work, a polymer matrix based on the CHT-Cu2+ complex was prepared. To increase the efficiency of incorporating the antitumor drug into the matrix, composite microparticles were prepared with the addition of an inorganic filler (hydroxyapatite, HAp). The electrospraying method was used to produce highly spherical microcarriers based on CHT-Cu/HAp composite due to its simplicity and high efficiency. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction analysis (XRD) were used to investigate the structure and composition of the obtained microspheres. The shape, size and size distribution of microparticles were determined using a scanning fluorescence microscope. The swelling degree of the microparticles was determined in phosphate buffer solution with pH values of 6 (PB-6) and 7.4 (PB-7.4) and demineralized water (H2O, pH 6.5). Incorporation of the antitumor drug (doxorubicin, DOX) was carried out in a slightly acidic medium for one or three hours at
37 °C, and the properties of the drug loaded-microparticles were examined using a fluorescence microscope, fluorescence spectrometry and gravimetric method. XRD and FTIR analyses showed the presence of hydroxyapatite in the prepared CHT-Cu/HAp composite and the microparticles obtained by the electrospraying process were spherical with an average particle size of 67.5 ± 25.6 μm for the CHT-Cu system and 72.1 ± 17.6 μm for the CHT-Cu/HAp system. The swelling study showed that the microparticles swell the most in an acidic medium, while the swelling degree increases with the addition of hydroxyapatite.
Using fluorescence microscopy, successful incorporation of doxorubicin into CHT-Cu and
CHT-Cu/HAp microparticles was observed. The results of fluorescence spectrometry and gravimetric method indicated the presence of phosphate salts in the microparticles.
The obtained results showed that the prepared composite microparticles can serve as potential drug delivery systems.
Keywords
kitozan
dostava lijeka
hidroksiapatit
doksorubicin
Keywords (english)
chitosan
drug delivery
hydroxyapatite
doxorubicin
Language croatian URN:NBN urn:nbn:hr:149:541461 Project Number: UIP-2020-02-6201 Study programme Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2024-02-29 10:27:08
