Optimization of aptamer-based manganese doped zinc sulphide/chitosan and carbon dots/chitosan as drug nanocarriers for controlled release of Mitomycin C
Drug delivery system (DDS) using nanocarriers have gained immense acclamation as a new prospect in nanomedicine. Conventional free drug delivery is associated with low therapeutic windows and inadequate therapeutic efficiency. Nanocarriers is outlined as a platform to combat such hurdles by tran...
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| Format: | Thesis |
| Language: | English |
| Published: |
2024
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/118473/ http://psasir.upm.edu.my/id/eprint/118473/1/118473.pdf |
| Summary: | Drug delivery system (DDS) using nanocarriers have gained immense
acclamation as a new prospect in nanomedicine. Conventional free drug
delivery is associated with low therapeutic windows and inadequate
therapeutic efficiency. Nanocarriers is outlined as a platform to combat such
hurdles by transporting and releasing the drug precisely at the target site with
maximum efficiency and safety in controlled manner. Therefore, in the present
work, DDS based on hybrid two types of quantum dots (QDs); manganese
doped zinc sulphide (Mn:ZnS) and carbon dots (CDs); incorporated onto
chitosan (CS) as drug nanocarriers for Mitomycin C (MMC), further conjugated
with aminated aptamer (Apt02); MMC@Mn:ZnS/CS-Apt02 and
MMC@CDs/CS-Apt02 have been successfully synthesized. The
physicochemical characterizations of nanocarriers were assessed using fieldemission
scanning electron microscopy (FESEM), High Resolution
Transmission Electron Microscopy (HRTEM), and Fourier Transform Infrared
Spectroscopy (FTIR). The morphological analysis shows that both DDS
exhibited nearly spherical shape with average particle size ranging from 80 to
110 nm. Subsequently, FTIR results reveals that there is slight shifting in
absorbance peak at 1646cm-1 in both DDS due to the formation of hydrogen
bond between amide group in MMC with hydroxyl group in chitosan. The drug
encapsulation efficiency and drug release studies were further evaluated using
UV-Vis Spectroscopy at 362 nm. The highest encapsulation efficiency were
obtained as 82.6 ± 2.2% and 83.7 ± 0.7% for MMC@Mn:ZnS-CS and
MMC@CDs-CS, respectively. The cumulative drug release percentages at pH
5.5 were 82.86 ± 1.33, and 81.44 ± 2.41 for MMC@CDs-CS-Apt02, and
MMC@Mn:ZnS-CS-Apt02, respectively. Preliminarily, the binding affinity of
two sequences of aptamers, Apt01 and Apt02 towards Vascular Endothelial
Growth Factor Receptor 1 (VEGFR1) have been assessed. From molecular
docking and experimental analyses, Apt02 exhibit better binding affinity
towards the VEGFR1. Hence, Apt02 has been used for the conjugation with
TDDS. Finally, the interaction of DDS towards synthetic VEGFR1 were
evaluated using fluorescence spectroscopy. An intense emission peak
centered at 610 nm and 430 were observed for MMC@Mn:ZnS/CS-Apt02-
VEGFR1 and MMC@CDs/CS-Apt02-VEGFR1, respectively. These DDS were
used in proof-of-concept studies as a possible application in targeted drug
delivery application. |
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