Biomedical Engineering Reference
In-Depth Information
erosion and diffusion processes.
118
The method of drug incorporation into the
NM delivery system also affects the release profile.
Drug release when loaded by covalent attachment on the particle system is
affected almost solely by drug-NM diffusion. This system has a relatively small
burst effect and sustained release characteristics.
119
When the drug is encapsu-
lated inside a NM, the release is controlled by diffusion of the drug from the
NM interior.
The polymer coating acts as a drug release barrier; hence, the drug solubility
and diffusion in or across the polymer membrane becomes a determining factor
in drug release. The release rate can also be affected by ionic interactions between
the drug and secondary ingredients. In the event that polymer-encapsulated drug
interacts with auxiliary ingredients, a less water-soluble complex may form
causing a slower drug release that almost has no burst release effect.
62
On the
other hand, addition of auxiliary ingredients, e.g. ethylene oxide-propylene
oxide block copolymer (PEO-PPO), to chitosan (CS) reduces the interaction
of the drug with the matrix material via competitive electrostatic interaction of
PEO-PPO with CS, and an increase in drug release could be achieved.
61
In an encapsulated drug where the drug is uniformly distributed inside the
NM matrix, drug release occurs by diffusion and/or erosion of the matrix. When
the diffusion of the drug is faster than matrix erosion, diffusion largely controls
the mechanism of release. The rapid, initial release, or “burst,” is mainly attrib-
uted to weakly bound or adsorbed drug to the relatively large surface of NMs.
120
There are several in vitro methods that can be used to study the release of
drugs loaded in an NM. These include: (1) side-by-side diffusion in cells with
artificial or biological membranes, (2) diffusion through a dialysis bag, (3)
reverse dialysis bag diffusion, (4) agitation followed by ultracentrifugation or
centrifugation, (5) ultrafiltration, or (6) pH change. In general, drug release
study is carried out by controlled shaking to allow the drug to ooze out of the
NM into a release media followed by centrifugation to separate the NM from
the drug in solution. However, the difficulties in the separation of NMs from
the release media favor the use of the dialysis technique. Exception to these
is the use of IOMNPs where loading with drugs is performed at high pH and
drug is released at low physiological pH. After the drug release, the IOMNPs
can easily be separated from the media with the use of magnets (SuperMag,
Ocean NanoTech) and the concentration of drug in the release media can be
established depending upon the properties of the drug (unpublished paper,
Ocean Nanotech).
Only a few studies have been published on drug release,
118,121
especially on
the release mechanisms. The mechanisms on in vitro drug release were gener-
ated by studying the model drugs tetracaine, etomidate, and prednisolone.
66
,
122
However, lipid NMs exhibited burst release when incorporating tetracaine and
etomidate. A prolonged drug release was obtained first with prednisolone that
demonstrated the suitability of the solid lipid NMs for prolonged drug release.
Drug release can be controlled as a function of the lipid matrix, surfactant
