Mukopenetrativne nanočestice cefiksima

master's thesis

• Title (english): Mucus-penetrating nanoparticles of cefixime
• Author: Severina Jajčević
• Mentor: Mario Jug (mentor)
• Committee member: Mario Jug (predsjednik povjerenstva)
• Committee member: Anita Hafner (član povjerenstva)
• Committee member: Živka Juričić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2017-05-02, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Svrha ovoga rada bila je priprava mukopenetrativnih nanočestica antibiotika cefiksima, njihova fizička karakterizacija nakon PEGiliranja i liofilizacije te određivanje postotka najboljega uklapanja lijeka u nanočestice. Također, budući da je u eksperimentalnom dijelu rada za određivanje sadržaja cefiksima korištena HPLC metoda, prije samoga ispitivanja proveden je njezin razvoj i validacija.
Nanočestice su načinjene uporabom Gantrez™ AN-169, anhidridnog polimera, te su PEGilirane PEG-ovima različite molekulske mase; PEG 4 000, PEG 6 000 I PEG 10 000. PEGiliranje stabilizira suspenziju nanočestica koje bi u suprotnome u vodenom mediju bubrile i otopile se. Veličina nanočestica ne prelazi 200 nm, što zadovoljava kriterij za postizanje optimalnog terapijskog učinka. Iznos zeta potencijala u sva tri uzorka PEGiliranih nanočestica veći je od -40 mV , no zbog negativnoga naboja na mucinima, ne očekuje se vezanje nanočestica na sluz. Sukladno očekivanjima, indeks polidisperznosti, izmjeren nakon oblaganja nanočestica, bio je manji od 0,2 te je time dobivena potvrda da se radi o monodisperznom sustavu. Kod nanočestica PEGiliranih PEG-om 6 000 povećanje indeksa polidisperzosti nije statistički značajno te se upravo kod tih nanočestica zamjećuje najveći postotak uklapanja cefiksima koji iznosi oko 10%. Iz navedenoga proizlazi da su nanočestice obložene PEG-om 6 000 najpogodnije za nastavak istraživanja.

Abstract (english)

The aim of this study is to prepare mucopenetrating nanoparticles of the antibiotic cefixime and perform their physical characterisation after pegylation and lyophilization, as well as to determine the percentage of drug in the most fitting nanoparticles to achieve maximum bioavailability and, according to that, a better therapeutic effect. Moreover, since in the experimental part of the work for cefixime determination was used HPLC method, prior to the tests it has been carried out its development and validation. Nanoparticles were formed using Gantrez™ AN-169, anhydrous polymer and then. PEGylated with PEGs of different molecular weight; PEG 4000, PEG 6000 and PEG 000. PEGylation stabilizes a suspension of nanoparticles which would otherwise swell in aqueous medium and dissolve. Nanoparticle size does not exceed 200 nm, which meets the criteria for achieving optimal therapeutic effect. The amount of zeta potential in all three samples of PEGylated nanoparticles is greater than -40 mV, but due to the negative charges on the mucins, it is not expected to bind the nanoparticles in the mucus. As hypothesized, polydispersity index, measured after coating nanoparticles was less than 0,2, and it is, thereby, it is confirmed that the system is monodispersed. When nanoparticles were PEGylated with PEG 6000, the increase in polydispersity index is not statistically significant and the administration of these nanoparticles noticing the highest incorporation percentage of cefixime, of about 10%. The abovementioned facts show that the nanoparticles coated with PEG 6000 most appropriate system for the further research.

• Keywords: mukopenetrativne nanočestice; sluznica; mucini; cefiksim; uklapanje lijeka; polietilenglikol
• Keywords (english): mucopenetrating nanoparticles; mucus; mucins; cefixime; drug incorporation; polyehylene glycol
• Language: croatian
• URN:NBN: urn:nbn:hr:163:711855
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-20 13:44:44