DEVELOPMENT OF MITOCHONDRIAL-TARGETED DRUG DELIVERY SYSTEM
Mitochondria are organelles surrounded by a double membrane and are present in almost all eukaryotic cells and are described as producing energy sources in the cell. In addition, mitochondria have an important role in cell cycle regulation including cell growth, proliferation, differentiation and...
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| Format: | Theses |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/62900 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Mitochondria are organelles surrounded by a double membrane and are present in almost
all eukaryotic cells and are described as producing energy sources in the cell. In addition,
mitochondria have an important role in cell cycle regulation including cell growth,
proliferation, differentiation and cell death. Mitochondria dysfunction contributes widely
to a number of disorders in the human body. Ranging from neurodegenerative,
neuromuscular, obesity, diabetes to ischemia-reperfusion and cancer. In this study, a
liposome-based mitochondrial-targeted nanocarrier system was developed with a
composition of 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE) as the main lipid
and cholesterol as an auxiliary lipid, which was conjugated with a mitochondrial agent,
namely dequalinium (DQA). The results of the size characterization of Liposom-DQA
(LipoDQ) nanoparticles obtained from this study were 124.50 ± 4.95 nm with a
polydispersity index of 0.25 ± 0.05. While the zeta potential measurement results obtained
are +11.40 mV, this positive value indicates the successful incorporation of dequalinium
into the liposome structure. This characterization was then confirmed by TEM
measurements which showed a spherical shape of the particles with sizes below 200 nm.
Observations on confocal microscopy on TM4 cells revealed the presence of LipoDQ
localization in the mitochondria. This was confirmed by the presence of bright yellow
fluorescence indicating the composition of red and green fluorescence, and indicating the
co-localization of nanocarriers into mitochondria. Furthermore, the high value of Pearson's
Coefficient LipoDQ (0.73 ± 0.05) indicated that most of the nanocarriers were localized in
mitochondria. The results of the characterization of LipoDQ containing quercetin obtained
a particle size of 147.90 ± 4.49 nm with a polydisperity index of 0.24 ± 0.58, a zeta potential
value of + 5.35 ±1.26 mV and an entrapment efficiency of 32.84 ±10.55%. The antioxidant
activity of quercetin which was incorporated into the LipoDQ nanocarrier system showed
antioxidant activity that was not much different from the antioxidant activity of free
quercetin where the inhibitory concentration (IC50) values produced were 2.95 ± 1.73 µM
and 3.33 ± 0.43 µM, respectively.
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