Chemistry Reference
In-Depth Information
hypothesized that this was because the encapsulated enzyme was more resistant to
denaturization in the 20% dioxane reaction solution.
8.4. DRUG DELIVERY WITH MICROCAPSULES
Delivering pharmaceutical agents to specific cells in the body is a difficult task invol-
ving complex interactions between many elements. Delivery systems have several
fundamental requirements to achieve this task. The delivery vehicle must be ingesti-
ble, implantable, or injectable to introduce the drug into the body. The system must
then protect the drug from the body's defense mechanisms in order to accumulate in
selected cells. Once at the target, the delivery system should release the enclosed
pharmaceutical agent with a controllable and predictable profile. Finally, the delivery
vehicle should be biocompatible, nontoxic, and easily eliminated from the body.
Polymeric capsules can meet many of these requirements for drug-delivery
vehicles. Most are small enough to be easily delivered into the body via ingestion
or either intravenous or subcutaneous injection. Small microcapsules and nanocap-
sules circulate safely in the cardiovascular system, which can thoroughly mix the
body's blood in minutes (Saltzman 2001). Generally, a microencapsulated pharma-
ceutical agent injected intravenously will reach every capillary in the body in
roughly 5 min. Moreover, many microcapsule materials offer protection from the
body's defense mechanisms, such as the liver's Kupffer cells (Hole 1989) and
specialized immune cells called phagocytes (Becker et al. 1996) that break down
foreign material into simpler components. Particulates are marked for elimination
by antigens or specific complementary molecules that allow phagocytes to bind to
the target material. Thus, a major theme in microcapsule drug-delivery applications
is surface functionalization to avoid recognition by the immune system. Additional
tuning of microcapsule characteristics can be used to change the biodistribution of
pharmaceutical-bearing microcapsules, and tuning the shell composition and struc-
ture is an effective way to control drug-release profiles. Finally, many of the polymers
used for drug microencapsulation are either derived from biological sources, and thus
inherently biocompatible, or degrade easily into smaller molecules that are easily
eliminated from the body. In the following sections, divided into specific encapsula-
tion methods and materials, we will discuss how polymeric nano- and microcapsules
have been successful in both laboratory and clinical settings as delivery vehicles for
pharmaceutical agents.
8.4.1. Homogeneous Particles
Although homogeneous solid particles constitute a major class of microparticles used
for the encapsulation of pharmaceutical agents, we will not discuss these materials in
detail because of their noncapsular nature, mentioning them here to only provide per-
spective. Many solid particles are based on poly(lactic acid), poly(lactic-co-glycolic
acid) (PLGA), and/or polyanhydrides and these have been developed especially by
several research groups (Ogawa et al. 1988; Tabata and Ikada 1988; Pekarek et al.
