Download Insulin/ Gold Nanoparticle Bonding Interactions: The nature of the

Insulin/ Gold Nanoparticle Bonding Interactions:
The nature of the binding of insulin to gold nanoparticles provides an
important aspect that affects the stability as well as the facility in which
release of insulin from gold nanoparticles occurs. Current research has
proposed nanoparticle formulations in which convalent linkages of insulin is
bound to the gold nanoparticles as well as formulations through the
interaction of hydrogen bonding with amino acid capped gold nanoparticles
(Scheme 1).
Direct covalent binding of insulin to the gold nanoparticle surface occurs
through amine or thiol groups which appear on the gold nanoparticle surface.
In contrast, formulations in which gold nanoparticles are capped with aspartic
acid produce weaker hydrogen bonding interactions, causing facile release of
insulin. Research has shown that insulin bound to bare gold nanoparticles
through covalent linkages has a lower success rate (86%) in comparison to
aspartic acid capped gold nanoparticles (95%). The weaker hydrogen bonding
and electrostatic interactions are responsible for the faster and larger release
of insulin.
Reference: Langmuir 2006 article
Effect of Gold Nanoparticles on Insulin Delivery-Subcutaneous Delivery Vs.
Oral and intranasal delivery:
In subcutaneous administration of insulin, a rapid decrease is observed in blood
glucose levels from 38% to 53% after administration. In oral administration of
insulin bound to gold nanoparticles as well as aspartic acid capped gold
nanoparticles, a reduction in blood glucose levels of 19% and 31% respectively is
observed, showing that insulin is bioactive and the aspartic acid capped gold
nanoparticle surface enhances insulin uptake. However intranasal administration of
insulin did not result in decrease in blood glucose levels, although when gold
nanoparticles and aspartic acid gold nanoparticles were used to deliver insulin, a
reduction of glucose level was observed of 50% and 55% respectively. Within
intranasal delivery, the release rate of insulin produced maximum blood glucose
reduction 180 minutes after administration when gold nanoparticles were used. The
use of aspartic acid gold nanoparticles showed that there is a more rapid release of
insulin when aspartic acid capped gold nanoparticles are used in which the
maximum blood glucose reduction occurred after 120 minutes. This result also
shows that the there is a greater membrane permeability of gold nanoparticle
insulin formulations across mucosal cells in comparison to gastrointestinal mucous.
By comparing subcutaneous administration in which a 53% reduction in blood
glucose levels was observed, to aspartic capped nanogold intranasal administration,
the results indicate that transmucosal delivery of insulin using gold nanoparticles is
an new alternative for insulin drug delivery in comparison to painful subcutaneous
delivery.
Reference: Langmuir 2006 article
Use/ Effects of Chitosan and Albumin
The design of nanoparticles for oral and intransally delivered insulin has shown to
be a new and innovative approach to the treatment of diabetes. Nanoparticles
produced by formulation of ionotropic pregelation have a multilayer complex where
insulin is protected within the nanoparticle with a coating consisting of proteaseprotective proteins. The nucleus of the particle consists of alginate, dextran sulfate,
and insulin, which is then complexed with chitosan, and coated with albumin.
Chitosan is a D-glucosamine and N-acetyl glucosamine polyamine, which is
unbranched. Chitosan displays properties such as mucoadhesion, biodegradability,
and biocompatible properties, which stabilize the formation of the nanoparticles.,
and prevent degradation The chitosan also reduce transepithelial electrical
resistance, which is caused by growth of epithelial tissues and can prevent the
effective delivery across the membrane. Other favorable properties of chitosan
include the ability to transiently open tight junctions which are found between
epithelial cells which results in enhanced insulin absorption through paracellular
pathways (transfer of substances between cells of the epithelium). Chitosan acts to
initiate and modulate insulin entrapment by incorporating polyanionic polymers
such as dextran sulfate. These polyanionic polymers also act to increase stability,
retention, and release of insulin in the gastrointestinal tract by enhancing the
electrostatic interactions between the nucleus of the nanoparticle and the insulin
molecules.
The albumin coating is used to minimize acid degradation of the nanoparticle
containing insulin which is a target for enzymatic degradation. The concentration of
albumin present also has an influence on the efficiency of the entrapment of insulin.
The most efficient insulin entrapment occurred (100%) when albumin
concentration was between 0.25% and 0.50%. The ability to trap the insulin
molecules appears to decrease as the concentration of albumin is increased which is
likely due to a consequent rise in pH of the nanoparticle, reaching the isoelectric
point of insulin and decreasing the electrostatic interaction between the insulin and
the nanoparticle.
The rate of release of insulin is also affected by the chitosen and albumin
concentrations. Higher chitosan concentrations influenced the rate of insulin release
by causing the nanoparticle to swell. Ions present in the gastric fluid inside the
nanoparticles break the ionic interaction between the insulin and the nanoparticles.
When there is a high concentration of albumin present, there is a higher insulin
release due to weakening of the electrostatic interaction between insulin.