Biomedical Engineering Reference
In-Depth Information
with a concomitant increase in white blood cells to four times baseline. The bioavail-
ability was 45.9% of the administered dose, and 62.0% of the dose reached the lung
lobes. In a study that compared pulmonary administration of r-huG-CSF powder with
solution [237], a normal systemic response was obtained, indicating that r-huG-CSF
retains its activity in the solid state after formulation. Dissolution and absorption of
r-huG-CSF from powders were not rate limiting, because the plasma concentration
versus time profiles peaked at similar times in both powder and solution administra-
tion. A study on the effects of PEGylation of rhG-CSF and the method of delivery
(aerosolization and instillation) on the bioavailability of rhG-CSF by pulmonary route
concluded that with both PEGylated and non-PEGylated proteins, the C max values and
T max values were affected by the delivery method and aerosol administration resulted
in higher concentrations and earlier T max values. The researchers concluded that the
response to single doses of rhG-CSF in healthy animals (hamsters, rats, and rabbits)
had shown no undesirable consequences with the exception of a transient increase in
both interstitial and airway granulocytes that appeared to be dose related.
9.6.2.7 Pancreatic Islet Autoantigen Insulin
Delivery
of aerosols that contain soluble immunologically active self-antigens such
as collagen and myelin-basic proteins to the respiratory tract has been suggested as
therapy for autoimmune diseases such as rheumatoid arthritis and multiple sclerosis,
as a result of the induction of systemic tolerance. Such an approach may be extended
to diabetes mellitus. In a study of mucosal tolerance in autoimmune diabetes using the
nonobese diabetic mouse model, Hanninen and Harisson [238] reported that treatment
of prediabetic mice with the pancreatic islet autoantigen insulin by aerosol (MMAD
m) inhalation reduced the incidence of diabetes. The reduction was associated
with induction of CD8
5.8
μ
γ
δ
T cells, small numbers of which prevent adoptive transfer
of diabetes. Regulatory
T cells secrete interleukin-10 in pancreatic lymph nodes,
which could account for the antidiabetic and bystander suppressor effect of nasorespi-
ratory insulin [239].
γ
δ
9.7 Conclusion
Drug
delivery is one of the most dynamic and fastest growing sectors of the pharma-
ceutical industry. In recent years, there has been a plethora of emerging novel drug
delivery technology companies. Most of these technologies are addressing issues
related to exclusive delivery systems and specific selection of these systems for effi-
cient treatment of diseases. Selection of the appropriate route of administration and
delivery device is critical for the commercial success of a drug product. In view of
these delivery systems, it is essential that the device design and formulation should be
integrated in the overall design and development of the product. However, improve-
ments in drug therapy are not only occurring through the development of new chemi-
cal molecules but also by the combination of a suitable active chemical entity and a
delivery system. More emphasis should be put on the improvement of the drug effect
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