Kinetika otpuštanja antitumorskog lijeka iz kompozitnih mikronosača

undergraduate thesis

• Title (english): Realease kinetics of antitumor drug from composite microcarriers
• Author: Edina Abdii
• Mentor: Anamarija Rogina (mentor)
• Committee member: Anamarija Rogina (predsjednik povjerenstva)
• Committee member: Iva Bazina (član povjerenstva)
• Committee member: Marica Ivanković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2024-09-11, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Ljudsko tkivo nema mehanizam obrane od stanica raka i njihovih brzih replikacija. Jedan od primarnih načina suzbijanja takve zloćudne abnormalnosti je izravno uklanjanje nastalog tkiva raka, primjena kemoterapije (antitumorskih lijekova) ili zračenje. Doksorubicin (DOX), kemoterapijski lijek, a i njegovi bioaktivni derivati su među najraširenijim lijekovima za takve tretmane. Razvoj manje invazivnih, „pametnih“ materijala, poput sustava za dostavu lijekova, nastao je iz potrebe za naprednim postupcima liječenja tumora. Isporuka lijeka sa ciljanom dostavom osigurava lokalizirano liječenje tumorskog tkiva, minimizirajući izloženost cijelog tijela. Kitozan (CHT) je poznat po svojoj biokompatibilnosti, hidrofilnosti, netoksičnosti i biorazgradljivosti. Štoviše, kitozan ima polikationsku prirodu zbog prisutnih amino skupina, što omogućuje oslobađanje lijeka iz polimernih matrica ovisno o pH vrijednosti medija te osigurava unutarstaničnu dostavu antitumorskih lijekova. U ovom radu istražen je utjecaj različitih inkubacijskih medija na profil otpuštanja antitumorskog lijeka (doksorubicina) iz pripremljenih kompozitnih materijala na temelju hidroksiapatita i kitozana fizikalno umreženog bakrovim(II) ionima (CHT-Cu/CaP), primjenom fluorescentne spektrofotometrije. Otpuštanje DOX-a iz mikročestica različitog kemijskog sastava (0, 5 i 10 mas.% CaP-a) praćeno je tijekom 72 h u fosfatnom puferu pH vrijednosti 6 (PB-6) i 7,4 (PB-7,4) te u mediju za staničnu kulturu (CCM). Dobiveni rezultati ukazuju na veće otpuštanje lijeka iz mikročestica s najvećim udjelom anorganske faze (CHT-Cu/CaP10), a najmanja količina DOX-a je otpuštena iz mikročestica bez dodatka CaP-a (CHT-Cu/CaP0). Medij u kojem je otpuštena najveća količina doksorubicina je medij za staničnu kulturu (CCM), a prati ga PB-6 pa PB-7,4. Takvi rezultati se pripisuju stabilnosti mikronosača zbog stabilnost kalcij-fosfata i ograničene topljivosti kitozana pri fiziološkim uvjetima. Dobiveni rezultati ukazuju na to da kemijski sastav mikronosača, kao sastav i pH inkubacijskog medija, utječu na profil otpuštanja lijeka, te da CHT-Cu/CaP mikročestice imaju veliki potencijal za upotrebu kao dostavljači doksorubicina za ciljanu isporuku lijeka pri liječenju raka kosti.

Abstract (english)

Human tissue lacks a defense mechanism against cancer cells and their rapid replication. One of the primary ways to combat such malignant abnormalities is through direct removal of the resulting cancer tissue, application of chemotherapy (antitumor drugs), or radiation. Doxorubicin (DOX), a chemotherapeutic drug, and its bioactive derivatives are among the most widespread drugs for such treatments. The development of less invasive, “smart” materials, such as drug delivery systems, arose from the need for advanced tumor treatment methods. Targeted drug delivery ensures localized treatment of tumor tissue, minimizing exposure to the entire body. Chitosan (CHT) is known for its biocompatibility, hydrophilicity, non-toxicity, and biodegradability. Moreover, chitosan has a polycationic nature due to the presence of amino groups, which allows drug release from polymeric matrices depending on the pH value of the medium, ensuring intracellular delivery of antitumor drugs. This study investigates the impact of different incubation media on the release profile of the antitumor drug (doxorubicin) from prepared composite materials based on hydroxyapatite and chitosan physically cross-linked with copper (II) ions (CHT-Cu/CaP), using fluorescence spectrophotometry. The release of DOX from microparticles of different chemical compositions (0, 5, and 10 wt.% CaP) was monitored over 72 hours in phosphate buffer solution at pH 6 (PB-6) and 7.4 (PB-7.4), as well as in cell culture medium (CCM). The results indicate greater drug release from microparticles with the highest amount of the inorganic phase (CHT-Cu/CaP10), while the smallest amount of DOX was released from microparticles without CaP (CHT-Cu/CaP0). The medium in which the largest amount of doxorubicin was released is cell culture medium (CCM), followed by PB-6 and then PB-7,4. Such results are attributed to the stability of the microcarriers due to the stability of calcium phosphate and limited solubility of chitosan under physiological conditions. The obtained results indicate that the chemical composition of microcarriers, as well as composition and pH value of the incubation medium influence the drug release profile, and suggest that CHT-Cu/CaP microcarriers have immense potential for use as doxorubicin delivery systems for targeted drug delivery in bone cancer treatment.

• Keywords: kitozan; kalcij-fosfatna biokeramika; mikročestice; doksorubicin; dostava lijeka; pH vrijednost
• Keywords (english): chitosan; calcium phosphates-based bioceramics; microparticles; doxorubicin; drug delivery; pH value
• Language: croatian
• URN:NBN: urn:nbn:hr:149:170498
• Project: Number: UIP-2020-02-6201; Title: Pametni sustavi za dostavu lijeka pri liječenju tumora kosti; Title: Smart drug delivery systems in bone tumour treatment; Acronym: SmartCar; Leader: Anamarija Rogina; Jurisdiction: Croatia; Funder: Hrvatska zaklada za znanost; Funding stream: Installation Research Projects
• Study programme: Title: Materials Science and Engineering - Undergraduate study; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka kemijskog inženjerstva (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-06-30
• Repository: Repository of Faculty of Chemical Engineering and Technology University of Zagreb
• Created on: 2024-11-14 10:37:03