Biomedical Engineering Reference
In-Depth Information
Pills, injections, suppositories, patches, topical ointments, and implantable fi xtures constitute
the common forms of drug administration. Each of these forms of administration imposes its own
set of requirements and has its own limits. For example, the oral dosage form is probably the most
preferred form but it is not suitable in the case of many drugs (such as proteins and nucleic acids)
that degrade or are not absorbed effi ciently within the gastrointestinal tract. Drugs that are not
deliverable orally are usually administered by intravenous, intramuscular, or subcutaneous injec-
tions or implants, depending on the formulations and their applications.
Drug delivery systems must be carefully designed on the basis of the nature of agents and tis-
sue sites to package agents into the systems. The drug delivery systems must be able to a) load the
appropriate amount of active agents for optimal availability and therapeutic effi cacy, b) avoid any
leakage during transport to the target, c) protect the incorporated active agents from degradation
before reaching the target, and d) achieve the proper release rate at the target. The release rate of
a drug depends on numerous bioenvironmental conditions such as pH, circulation of fl uid, viscos-
ity, temperature, ionic strength, adsorption of specifi c or nonspecifi c biomolecules, and local redox
potential of the surrounding medium. In the case of a self-regulated system, the drug delivery
method must integrate the biosensing function with the release system in response to changes in the
local bioenvironment. The ideal drug delivery system should also be mechanically strong, simple to
administer and remove, and easy to fabricate and sterilize. Finally, the drug delivery system must
satisfy long-term toxicological requirements and be comfortable for the patient.
In general, the purpose of controlled drug delivery is to optimize the medicine's effective-
ness and eliminate the possibility of underdosing or overdosing. Controlled-delivery systems can
help to maintain drug levels within a desired range, reduce the frequency of administrations, and
increase patient compliance. In contrast, the potential disadvantages of controlled-delivery systems
are toxicity, need for surgery to implant or remove the system, patient discomfort from the delivery
device, and higher cost.
Traditional controlled-delivery systems have used a range of polymer materials as key compo-
nents to achieve both temporal- and distribution-controlled release. Temporal-controlled release
is usually achieved by delaying the dissolution of drug molecules, inhibiting the drug outward
diffusion, or controlling the fl ow of drug solutions (Figure 8.1).
4
To achieve distribution control,
polymeric drug carriers can simply be applied locally
5
(e.g., a photo-crosslinkable drug-retained
wound-healing hydrogel
6
), implanted directly at the site,
7
injected to a localized site and have the
polymer form a semisolid drug depot
in situ
8
(e.g., drug-containing photocrosslinkable hydrogels
injected to inhibit subcutaneous tumor growth
9
), or dispensed in the form of either colloidal par-
ticles or polymer-drug conjugates, where in either case, the polymer acts solely as a carrier and
usually has to adopt the targeting moieties such as immunoglobulins and carbohydrates.
4
As polymer-based drug carriers are designed, understanding the metabolism of the polymer in
the human body is vital in choosing the appropriate carriers for different applications. Nondegradable
polymers are acceptable for oral applications in which the polymer passes through the gastrointestinal
tract or the delivery systems such as patch or insert that can be removed after drug release. In other
applications such as some drug delivery implants,
10
therapeutic aerosols,
3
drug or gene carriers circu-
lating in the blood system,
11
or
in situ
forming drug depot,
8,12
biodegradable polymers are desirable.
Polymers used in drug delivery were originally not intended for biological uses but were bor-
rowed for their suitable properties such as diffusivity, permeability, biocompatibility, solubility,
mechanical strength, and environmental sensitivity. For example, polyurethane is used for its
elasticity, polysiloxane or silicones for its biocompatibility and insulating ability, and poly(methyl
methacrylate) for its physical strength and transparency. Some other nondegradable polymers that
are in use or under study for controlled drug delivery include poly(2-hydroxy ethyl methacrylate),
poly(
N
-isopropyl acrylamide), poly(
N
-vinyl pyrrolidone), poly(carbophil), poly(vinyl alcohol),
poly(ethylene glycol), and poly(acrylic acid). The diffusion, dissolution, permeation, swelling, and
stimuli sensitivity characteristics of polymer materials have been used to obtain the constant release
of entrapped molecules.
4,13
