Citation
Othman, Nurhanisah
(2022)
Synthesis and optimization of palmitoyl-chitosan nanoparticles as a potent dual antioxidant carrier with hydrophobic and hydrophilic compounds.
Doctoral thesis, Universiti Putra Malaysia.
Abstract
Chitosan nanoparticles (CNP) is a potent delivery vector for hydrophilic
pharmaceuticals as it is biodegradable and biocompatible. In this study, it was
synthesized by a non-toxic and simple ionic gelation method that successfully
produced cationic, monodispersed spherical particles with an average size of
60.5 ± 2.1 nm and a polydispersity index (PDI) of 0.19 ± 0.02. The carrier was
dual encapsulated with antioxidants to diversify CNP ability as it is normally being
used for single encapsulation. Hydrophobic thymoquinone (TQ) and hydrophilic
L-ascorbic acid (LAA) were incorporated into the carrier to evaluate their
combination effects in scavenging free radicals when delivered using a
nanoparticle (NP) system. However, the encapsulation of hydrophobic TQ was
marred by the hydrophilicity of chitosan (CS). Thus, palmitic acid was conjugated
on the CS through hydrophobic modification, which produced palmitoyl-chitosan
nanoparticles (PCNP). The amphiphilic PCNP encapsulated with TQ and LAA
showed increased size, 247.7 ± 24.0 nm and PDI, 0.35 ± 0.04. It also had a
positive zeta potential of 19.60 ± 1.27 mV, which would make good interactions
with negatively charged cell membranes during antioxidants delivery. The
encapsulation efficiencies (EE) of TQ and LAA increased to 64.9 ± 5.3% and
90.0 ± 0.0%, respectively. The antioxidants followed zero order release kinetics
with a controlled release manner for about 48 h. Interaction effect between TQ
and LAA loaded in the NP system was determined by classical isobologram (CI)
values derived from diphenyl picrylhydrazyl (DPPH) assay. Combined TQ and
LAA had CI values of less than one with lower value in the PCNP system than
CNP. This indicates that the interaction between those antioxidants showed
higher synergistic effects in PCNP, which enhanced DPPH radical scavenging
activities. Additionally, reactive oxygen species (ROS) assay was experimented
on human normal lung fibroblast cell line, MRC-5 as lungs is one of the organs
with high accumulation of free radicals. About 48 h post treatment, the dual
loaded TQ and LAA in PCNP showed the lowest ROS level in comparison to
single loaded antioxidant and bare antioxidant delivery. The H2O2 radical scavenging was influenced by both controlled release property of the PCNP
system and synergy between TQ and LAA. In short, the dual loaded TQ and LAA
in the hydrophobically modified PCNP had successfully depicted the capability
to hold more than one compound at a time in a single CS based nanocarrier.
With this advancement, more highly efficacious compounds of different polarities
with poor systemic uptake could be encapsulated together in NP systems to
increase their pharmaceutical efficiency.
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Additional Metadata
Item Type: |
Thesis
(Doctoral)
|
Subject: |
Chitosan - Biotechnology |
Subject: |
Pharmaceutical technology |
Subject: |
Drug delivery systems |
Call Number: |
FS 2022 42 |
Chairman Supervisor: |
Associate Professor Siti Nurul Ain binti Md. Jamil, PhD |
Divisions: |
Faculty of Science |
Depositing User: |
Editor
|
Date Deposited: |
07 Jul 2023 02:40 |
Last Modified: |
07 Jul 2023 02:40 |
URI: |
http://psasir.upm.edu.my/id/eprint/104077 |
Statistic Details: |
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