Biomedical Engineering Reference
In-Depth Information
(blood, serum, plasma, urine, and feces) is rarely straightforward.
Ocular tissue bioanalysis, with an additional unique set of asso-
ciated challenges, is much more complex. Ocular tissue bioanalysis,
being invasive in nature, is typically conducted in preclinical studies.
The rabbit is the species most commonly utilized for ocular inves-
tigations; other species include guinea pig, pig, monkey, and dog.
The eye is among the most complex organs in the body and is
composed of several heterogeneous tissues and fluids including the
sclera, conjunctiva, cornea, lens, iris, ciliary body, choroid, retina,
aqueous humor, and vitreous humor. Classical tissue bioanalytical
studies often rely on the preparation and analysis of homogenates
of the entire organ or the representative sections of that organ.
However, the eye is typically dissected to obtain component tissues
and fluids for analysis. This is necessary due to the heterogeneity of
the eye and because ocular drug administration often requires the
placement of the dosed material relatively far from the site of action
within the eye; i.e., the administered drug may have to traverse
several tissue barriers and ocular fluids to reach its target tissue.
Measurements of drug concentrations from the site of administra-
tion through the various tissues and fluids leading to the targeted
tissue, along with the targeted tissue itself, provide critical informa-
tion about the drug and its formulation. These data are critical in
guiding lead candidate selection and in the development of appro-
priate pro-drugs or formulations for ocular administration to
ensure that sufficient drug is reaching the targeted site of action.
The eye is constructed of various physical and biological bar-
riers to absorption, which can be a challenge for drug delivery to
intended sites of action. Although therapies for ocular disorders can
be administered systemically, bioavailability to the eye is limited by
the blood-ocular barrier. Localized routes of administration,
including topical, periocular, and intravitreal, are usually required
to generate greater ocular tissue exposures. It is estimated that
approximately 80 % of a topically applied drug is washed away by
tears and enters the general circulation via the nasolacrimal canal or
is absorbed from the conjunctival sac via local blood capillaries.
Typically, less than 5 % of topically applied drug is bioavailable to
the eye [
1
-
5
]. Drugs can be directly injected into the eye (including
sub-conjunctival, sub-tenon, or intra-vitreal injections) or adminis-
tered by various ocular devices which are frequently implanted in
the vitreous cavity, outside the path of vision. The concentration of
drug and/or metabolites in systemic circulation following localized
ocular administration is usually low, often at or below the level of
detection of the analytical method being used. Hence, assessment
of systemic exposure may require the development of highly sensi-
tive bioanalytical methods for drug and metabolites in blood,
serum, or plasma.
Following intraocular absorption, some drugs distribute
rapidly and reach approximately equivalent concentrations in the
