Priprava i karakterizacija vezikularnog fosfolipidnog gela s timolom

postgraduate specialist thesis

• Author: Marica Jozić
• Mentor: Željka Vanić (mentor)
• Committee member: Jelena Filipović-Grčić (predsjednik povjerenstva)
• Committee member: Željka Vanić (član povjerenstva)
• Committee member: Ana Šešelja Perišin (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2024-03-26, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Cilj istraživanja
Cilj ovog istraživanja bila je priprava i evaluacija vezikularnog fosfolipidnog gela (VFG) s
timolom, namijenjenog dermalnoj primjeni. Optimizirani su uvjeti priprave VFG-a, te je ispitan
utjecaj sastava VFG-a na fizikalna svojstava vezikula (liposoma) unutar VFG-a, oslobađanje
timola i reološke karakteristike formulacija.
Materijali i metode
Eksperimentalni dio rada obuhvaćao je izradu VFG-ova s timolom različitog (fosfo)lipidnog
sastava metodom visokotlačne homogenizacije. Provedeno je određivanje fizikalno-kemijskih
svojstava VFG-ova s timolom (srednji promjer, indeks polidisperznosti, zeta potencijal
liposoma unutar VFG-ova) te ispitivanje topljivosti timola u različitim otapalima kako bi se
odredio prikladan medij za provođenje ispitivanja in vitro oslobađanja. Ispitivanja in vitro
oslobađanja timola iz odabranih formulacija VFG-ova i kontrole (otopina timola) provedena
su metodom dijalize, a oslobođeni timol je određen spektrofometrijski. Reološka
karakterizacija formulacija uključivala je rotacijska (profil viskoznosti) i oscilatorna (test
promjene amplitude) mjerenja.
Rezultati
Visokotlačnom homogenizacijom uz primjenjeni tlak od 500 bara pripravljena su dva različita
tipa VFG-a srednjih promjera liposoma od 140 do 200 nm i blago negativnog zeta potencijala
(-5 do -8 mV). Postignuto je produljeno oslobađanje timola iz oba tipa VFG-a u odnosu na
kontrolu, pri čemu je (fosfo)lipidni sastav značajno utjecao na udio oslobođenog timola.
Prisustvo kolesterola u formulaciji je rezultiralo polaganijim oslobađanjem timola u odnosu na
formulaciju pripravljenu isključivo iz sojinog fosfadilkolina. (Fosfo)lipidni sastav VFG-a
utjecao je i na reološka svojstva formulacija. VFG pripravljen bez kolesterola bio je neznatno
viskozniji u odnosu na VFG s kolesterolom, dok temperatura na kojoj su provedena mjerenja
nije utjecala na viskoznost formulacija. Oba tipa VFG-a su pokazala viskoelastična svojstva
prikladna za dermalnu primjenu (G' > G“ u linearnom viskoelastičnom području).
Zaključak
Rezultati provedenih ispitivanja u sklopu ovog rada ukazuju na mogućnosti primjene VFG-a
kao inovativne polučvrste podloge za dermalnu dostavu timola. Reološkom karakterizacijom
potvrđena su pseudoplastična svojstva pripravaka, kojima se omogućuje produljeno
oslobađanje timola. Daljnjim ispitivanjima (permeabilnost kroz kožu, antimikrobni učinak,
biokomaptibilnost) procijenila bi se prikladnost formulacija VFG-ova s timolom za primjenu
na kožu.

Abstract (english)

Objective
The aim of this research was to prepare and evaluate a vesicular phospholipid gel (VPG) for
dermal delivery of thymol. The preparation conditions of VPGs were optimized, and the impact
of the (phospho)lipid composition of the VPG on the release of thymol, physico-chemical
properties of the liposomes within the VPGs, and the rheological characteristics of the
formulations, was examined.
Material and Methods
Thymol-loaded VPGs of different (phospho)lipid composition were prepared using the highpressure homogenization method at applied pressure of 500 bar. The physicochemical
properties of liposomes within the thymol-loaded VPGs were determined (mean diameters,
polydispersity indexes, zeta potentials) and the solubility of thymol in different solvents was
tested in order to determine a suitable medium for conducting in vitro release studies. In vitro
release of thymol from the selected VPGs and the control (thymol solution) were performed
using the dialysis method, while the released thymol was determined spectrophotometrically.
Rheological characterization of the formulations included rotational (viscosity profile) and
oscillatory (amplitude test) measurements.
Results
Two different types of VPGs, with liposomes exhibiting mean diameters of 140 - 200 nm and
a slightly negative zeta potentials (-5 to -8 mV), were prepared by high-pressure
homogenization method. Prolonged release of thymol from the both types of VPGs was
achieved compared to the control, whereby the (phospho)lipid composition had a significant
effect on the release of thymol. The presence of cholesterol in the VPG resulted in a slower
release of thymol compared to the VPG prepared exclusively from soy phosphadylcholine. The
(phospho)lipid composition of VPGs also affected the rheological properties of the
formulations. VPG prepared without cholesterol was slightly more viscous compared to VPG
with cholesterol, while the temperature at which the measurements were carried out did not
affect the viscosity of the formulations. Both types of VPGs showed viscoelastic properties
suitable for dermal application (G' > G“, in linear viscoelastic region).
Conclusion
The results of all conducted studies indicate the suitability of VPG as an innovative semisolid
vehicle for dermal delivery of thymol. The rheological characterization confirmed the
pseudoplastic properties of VPGs, which enabled the prolonged release of thymol. However,
further investigations are required, such as skin permeability studies, antimicrobial testing, and
biocompatibility assessment, to evaluate the suitability of thymol-loaded VPGs for skin
application.

• Keywords: vezikularni fosfolipidni gel: timol; dermalna primjena
• Keywords (english): vesicular phospholipid gel; thymol; dermal delivery
• Language: croatian
• URN:NBN: urn:nbn:hr:163:134061
• Study programme: Title: Drug development - specialistic study - university study; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni specijalist razvoja lijekova (sveučilišni specijalist razvoja lijekova)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-03-26
• Created on: 2024-06-14 08:56:46