Targeted Drug Delivery - Nanomaterials for Medical Applications - page 219

in biodegradable PLGA for intraspinal administration of glial cell line-derived
neurotrophic factor following contusive spinal cord injury and for in vitro
study. 154 Intraspinal delivery of neurotrophic factor encapsulated in biodegrad-
able PLGA NPs following contusive spinal cord injury were well absorbed by
neurons and glia showing PLGA as a useful nanocarrier delivery system for
neuroprotective polypeptide into the injured spinal cord.
One important requirement for NMs' brain delivery systems is that they are
rapidly biodegradable over a time frame of a few days. 213 Nonbiodegradable
particles such as fullerenes, toxic systems as heavy metal containing QDs, or
potentially risky drug delivery systems such as carbon nanotubes that may have
hazardous effects similar to asbestos, therefore, are not useful.
5.11 CONCLUSION
Drug delivery in cancer, tumor, and other types of diseases are important for
optimizing the effect of drugs and reducing toxic side effects. Several nano-
technologies, mostly based on NMs, can facilitate drug delivery to tumors.
However, such NMs have to be carefully and meticulously engineered before
they can perform the functions they are designed for. Excellent candidates as
nanocarriers must be small (less than 100 nm), nontoxic, biodegradable, bio-
compatible, does not aggregate, avoids the RES, and escapes opsonization, non-
inflammatory, with prolonged circulation time and cost effective. Many drugs in
the market that are now available for human use are already nano enabled. The
ability of these drugs to minimize the side effects that are normally observed in
conventional drugs open up doors for applications of NMs as safer alternatives
to drug delivery.
Aside from the requirements of size, charge, shape, surface modifications,
loading, and other chemical properties to effectively deliver drugs using the NM
carrier systems, other challenges need further attention. These studies need to
focus on the interaction of NMs and their hosts in terms of biodistribution, organ
accumulation, degradation and/or toxicity, damage of cellular structures or
inflammatory foreign body effects, and genetic damage. Aggregation or precipi-
tation once in contact with biological fluids in host animals or humans must be
carefully evaluated and its prevention are established to prevent adverse effects.
In a preliminary study, the author conducted a stability evaluation of IOMNPs
loaded with dox in fresh human whole blood (Z.P. Aguilar unpublished data).
The results indicated that properly coated with amphiphilic polymer, IOMNPs
loaded with dox are stable (left and middle wells) in fresh human whole blood
(treated with heparin to prevent coagulation) even after 24 h of exposure ( Figure
5.9 ). Without the proper coating, the IOMNP can be loaded with dox but aggre-
gation occurs upon exposure to blood (two wells on the right).
It is essential to investicate the possible adverse effects or toxicity of nano-
carriers. 217,218,219 But, the NM drug delivery system is still its infancy. Research
protocols like absorption, distribution, metabolism, and elimination (ADME),