Title Priprava mikročestica primjenom mikroreaktora Title (english) Preparation of microparticles using microreactors Author Zoran Malbaša 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 2024-07-12, Croatia Scientific / art field, TECHNICAL SCIENCES Abstract Cilj ovog rada bio je pripremiti mikročestice na temelju kompleksa kitozana i bakrovih(II) iona (CHT-Cu) primjenom mikroreaktora napravljenog de novo. Promjenom brzine protoka kontinuirane i dispergirane faze cilj je bio dobiti usku raspodjelu veličina mikročestica. U eksperimentalnom dijelu rada, strojnom obradom napravljen je mikroreaktor na temelju poli(metil-metakrilata) (PMMA) geometrije poprečnog protoka (T-spoj) s kanalima promjera 940 ± 50 μm. Kao dispergirana faza korištena je otopina CHT-Cu kompleksa, dok je kontinuirana faza bila suncokretovo ulje s ili bez emulgatora (SPAN 85). Ispitivan je utjecaj promjene brzine protoka kontinuirane i dispergirane faze kao i upotreba različitog sastava neutralizacijskog medija. Kao neutralizacijski medij je korištena 1,25 mol dm^-3 otopina natrijeva hidroksida (NaOH) ili smjesa otopine NaOH i 96 vol. % etanola (volumni omjer 1:1). Također, ispitivane su različite modifikacije mikroreaktora, kao što su primjena metalne igle i crijeva za lakše odvođenje produkta (otopine) na izlazu iz mikroreaktora, te primjena teflonskog sloja na izgled i veličinu nastalih CHT-Cu mikročestica. Dobivene CHT-Cu mikročestice bile su prosječne širine 567 ± 190 μm i dužine 1091 ± 250 μm, neovisno o primijenjenim brzinama protoka kontinuirane i dispergirane faze, ali različitog oblika uslijed upotrebe različitih sastava neutralizacijskog medija. Tijekom ispiranja i sušenja dolazi do smanjenja nastalih mikročestica uz zadržavanje nepravilnog, izduženog oblika, uz pojavu aglomerata. Infracrvena spektroskopija s Fourierovom transformacijom (ATR-FTIR) pokazala je prisutnost elektrostatskih sila između metalnih iona i polimernog lanca kitozana bez pojave dodatnih apsorpcijskih vrpci, što je potvrdilo uspješnost primijenjenog postupka ispiranja i sušenja mikročestica. Kao obećavajući sustav su se pokazale CHT-Cu mikročestice dobivene primjenom 1,25 mol dm^-3 NaOH i 96 vol.% EtOH kao neutralizacijskog medija, uz brzine protoka kontinuirane i dispergirane faze od 50 i 0,5 mL h^-1. Rezultati ovog rada ukazuju na potencijal korištenja mikroreaktora za dobivanje mikročestica na temelju kitozana i metalnih iona, a što može poslužiti kao podloga za daljnja istraživanja s ciljem optimizacije procesa kako bi se dobile mikročestice pravilnijih oblika s užom raspodjelom veličina, a za razvoj sustava za ciljanu dostavu lijekova.
Abstract (english) The aim of this study was to prepare microparticles based on chitosan-copper(II) ion complex (CHT-Cu) using a de novo microreactor. By manipulating the flow rates of the continuous and dispersed phases, the goal was to achieve a narrow size distribution of the CHT-Cu microparticles. In the experimental part of this study, a poly(methyl-methacrylate) (PMMA) microreactor with T-junction geometry and channels of diameter 940 ± 50 μm was prepared by surface machining technique using a milling machine. The dispersed phase was CHT-Cu complex solution, while the continuous phase was sunflower oil with or without an emulsifier (SPAN 85). The study examined the effects of varying the flow rates of the continuous and dispersed phases, as well as using different compositions of the neutralizing medium. The neutralizing medium was a 1.25 mol dm^-3 sodium hydroxide (NaOH) solution or a mixture of NaOH solution and 96 vol. % ethanol (volume ratio 1:1). Additionally, different modifications of the microreactor were tested, such as the use of a metal needle and a tube (pipe) for easier removal of the product (solution) from the microreactor’s outlet, and the use of a Teflon layer on the microreactor’s surface, on the size and shape of the resulting CHT-Cu microparticles. The obtained CHT-Cu microparticles were of average width 567 ± 190 μm and length 1091 ± 250 μm, regardless of the applied flow rates of the continuous and dispersed phases, but varied in shape due to the use of different compositions of the neutralizing medium. During washing and drying, the resulting microparticles decreased in size while retaining an irregular, elongated shape and the formation of agglomerates. Fourier-transform infrared spectroscopy (ATR-FTIR) indicated the presence of electrostatic forces between the metal ions and the chitosan polymer chain without the appearance of new absorption bands, confirming the success of the applied washing and drying procedures. CHT-Cu microparticles obtained using 1,25 mol dm^-3 NaOH and 96 vol.% EtOH as a neutralization medium, with continuous and dispersed phase flow rates of 50 and 0,5 mL h^-1 proved to be a promising system. The results of this study indicate the potential use of microreactors for obtaining microparticles based on chitosan and metal ions, which can serve as a basis for further research aimed at optimizing the process to produce micro-particles with more regular shapes and narrower size distribution, for the development of targeted drug delivery systems.
Keywords
kitozan
bakrovi(II) ioni
mikroreaktori
mikročestice
Keywords (english)
chitosan
copper(II) ions
microreactor
microparticles
Language croatian URN:NBN urn:nbn:hr:149:697795 Project Number: UIP-2020-02-6201 Study programme Title: Materials Science and Engineering - Graduate study Type of resource Text File origin Born digital Access conditions Embargoed access Terms of use Created on 2024-07-15 15:13:00
