Return to search

Hemocompatibility of N-trimethyl chitosan chloride nanoparticles / Lizl du Toit

Research on nanoparticles for pharmaceutical applications has become increasingly popular in
recent years. N-trimethyl chitosan chloride (TMC) is a cationic polymer that can enhance absorption
across mucosal surfaces. It has been explored as a nanoparticulate drug delivery system for the
delivery of vaccines, vitamins, insulin and cancer medication. It has special interest for intravenous
use, as it is soluble over a wide range of pH values. However, polycationic nanoparticles run a great
risk for intravenous toxicity, as the positive surface charge allows easy electrostatic interactions with
negatively charged blood components, such as red blood cells and plasma proteins. Additionally, the
small size of the nanoparticles permits the binding of more proteins per mass, than larger particles
do. These interactions can lead to extensive hemolysis, cell aggregation, complement activation,
inflammation and fast clearance of the particles from the circulation. A decrease in the surface
charge density can ameliorate these toxic interactions. Such a decrease is achieved by adding
poly(ethylene) glycol (PEG) to the particle’s formulation. PEG creates a steric shield around the
particles, preventing a certain extent of interaction between the particles and the blood
components.
To be able to use TMC nanoparticles as a successful drug delivery system, the hemocompatibility
must first be determined, which was the aim of this study. The influence of particle size,
concentration and the addition of PEG were also examined.
The extent of hemolysis and cell aggregation caused by the experimental groups (20% and 60%
concentration small TMC nanoparticles, 20% larger TMC nanoparticles and 20% cross-linked PEGTMC
nanoparticles) were determined by incubating the groups with whole blood and/or blood
components. Complement activation was determined with a Complement C3 Human enzyme-linked
immunosorbent assay (ELISA) and plasma protein interactions were quantified through rapid
equilibrium dialysis and a colorimetric assay.
It was determined that 60% concentration small TMC nanoparticles caused 49.08 ± 2.538%
hemolysis at the end of a 12-hour incubation period, significantly more than any other experimental
group. This group had also caused mild aggregation of the white blood cells and platelets. This was
the greatest extent of cell aggregation seen in any of the groups. No significant complement
activation was seen by any of the experimental groups. Because of the cationic nature of the particles, all groups had more than 50% of the initial particles in the sample bound to plasma
proteins after a 4-hour incubation period. However, at 90.68 ± 0.828%, the 60% small TMC
nanoparticles had had significantly more interaction with the plasma proteins than the other groups.
Through the experimental measurements it was revealed that TMC nanoparticles had hemotoxic
effects at high concentrations. The addition of PEG to the particle formulation stabilized the
particles and decreased their zeta potential , but had no significant effect on improving
hemocompatibility.
It was concluded that although further tests are needed, TMC nanoparticles seem to have potential
as a successful intravenous carrier for high molecular weight active pharmaceutical ingredients. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:nwu/oai:dspace.nwu.ac.za:10394/10711
Date January 2014
CreatorsDu Toit, Lizl
Source SetsSouth African National ETD Portal
LanguageEnglish
Detected LanguageEnglish
TypeThesis

Page generated in 0.0022 seconds