QbD approach for optimization and characterization of anti-glioblastoma drug embedded lipid nanoparticles for intranasal administration

Sabir Fakhara
QbD approach for optimization and characterization of anti-glioblastoma drug embedded lipid nanoparticles for intranasal administration.
Doctoral thesis (PhD), University of Szeged.

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Abstract in foreign language

This work aimed to develop novel lipid nano-formulations containing n-propyl gallate (PG) and lomustine (LOM) as a potential anti-glioblastoma drug combination. The first step was the application of the QbD for the optimization of the lipid-nanoparticles. The characterization studies of optimized liposomes and solid lipid nanoparticles (SLNs) were performed. Comparative studies of the developed formulations under simulated nasal conditions (in vitro cell line, ex vivo permeation, and cell uptake study) were performed. Optimization and characterization of the liposomal carrier with binary drug contents were carried out in order to achieve adequate encapsulation efficiency, loading capacity, drug release, and ex vivo permeation. Liposomes loaded with PG and LOM showed increased stability and efficacy in comparison to PG-LOM-loaded SLNs. Thus, the liposomal formulations were further applied for combination therapy. The optimized liposome co-encapsulated with both drugs showed suitable Z-average (127±3.3 nm), size distribution, polydispersity index of 0.142±0.20, the zeta potential of −34±2.3 mV, moreover high encapsulation efficacy (63.57±5.5 of PG and 73.45±6.5 of LOM, respectively) meeting the acceptance criteria of nose-to-brain delivery. MTT assays of PG-LOM formulations were also conducted on NIH/3T3 (murine embryonic fibroblast), U87 (glioblastoma), and A2780 (ovarian cancer) cell lines indicating a synergistic anti-proliferative effect on U87 (glioblastoma) when used in combination (PG-LOM Lipo). The cellular uptake study of liposomes loaded with propidium-iodide under fluorescent microscopic on U87 and U251 cell lines showed successful uptake of liposomes. These results support the evidence that the drug tends to enter the tumor cells and its release takes place within the cell.

Item Type: Thesis (Doctoral thesis (PhD))
Creators: Sabir Fakhara
Hungarian title: QbD Megközelítés alkalmazása az intranazális alkalmazású glioblasztoma ellenes hatóanyag tartalmú lipid nanorészecskék optimalizálására és karakterizálására
Position, academic title, institution
MTMT author ID
Csóka Ildikó
Habilitált doktor, Gyógyszertechnológiai és Gyógyszerfelügyeleti Intézet SZTE / GYTK
Subjects: 03. Medical and health sciences > 03.01. Basic medicine > 03.01.06. Pharmacology and pharmacy > Pharmaceutical development
Divisions: Doctoral School of Pharmaceutical Sciences
Discipline: Medicine > Pharmacy
Language: English
Date: 2022. August 30.
Item ID: 11308
MTMT identifier of the thesis: 34117962
doi: https://doi.org/10.14232/phd.11308
Date Deposited: 2022. May. 13. 09:03
Last Modified: 2023. Aug. 29. 13:50
Depository no.: B 7157
URI: https://doktori.bibl.u-szeged.hu/id/eprint/11308
Defence/Citable status: Defended.

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