Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 546

polydimethylsiloxane matrices can be modified by the addition of a hydrophilic pore-
building excipient, control of total matrix loading, and other conditions [133] . P/P that
have been investigated for their release behavior from silicone elastomers include insu-
lin, BSA, chymotrypsin, pepsin, and a dipeptide (Gly-Tyr) [135,136] . One of the most
commonly used nondegradable biocompatible polymers is EVAc because it offers con-
trol of the release rates of embedded polypeptides [137,138] . Single implants of insu-
lin-loaded EVAc devices have shown controlled release of insulin for up to 105 days
in diabetic rats [139] . These polymers have shown inertness in the body without any
toxicity, but because of their nonbiodegradability, they are required to be removed from
the targeted organ by surgery after the desired release period.
11.4.2 Biodegradable Polymers
Biodegradable polymeric systems present great potential for delivering many bio-
active agents, including P/P drugs. A number of different biodegradable polymers,
both synthetic and natural, have been utilized in formulating delivery systems for P/P
drugs [140-143] . Biodegradable block copolymers have proven to be very promis-
ing biomaterials by virtue of the ability to manipulate their amphiphilic behavior and
technical and physical properties by adjusting the ratio of the constituting block or
adding new blocks with desired properties. Hence, the general criteria for selecting a
polymer for use in a delivery system are to match the mechanical properties and the
degradation rate to the needs of the application [144] .
In general, synthetic polymers offer greater advantages than natural ones in that
they can be tailored to give a wider range of properties [145] . A large number of biode-
gradable polymers are used in the formulation of drug delivery systems for P/P drugs;
a list is provided in Table 11.1 . Some of those polymers, which are of considerable
importance or have found many applications, are covered in the following section.
11.4.2.1 Synth�ti� Po﻽ym��s
11.4.2.1.1 Polyester Polymers
The key features that have attracted investigators to these polymers include [146]
largely available toxicological and chemical data, biocompatibility/histocompat-
ibility, predictable biodegradation kinetics, ease of fabrication, versatility in prop-
erties, commercial availability, variety in copolymers ratios and molecular weights,
and lastly, and most importantly, regulatory approval [147] . In this chemical class
of polymers, polylactides (PLA) and PLGA have been the most extensively inves-
tigated for drug and protein delivery [148] . As polyesters in nature, these polymers
undergo hydrolysis by an acid- or base-catalyzed reaction upon implantation into the
body, forming biologically compatible and metabolizable moieties (lactic acid and
glycolic acid) that are eventually removed from the body by the Krebs or citric acid
cycle. D-lactic acid is generally excreted intact. The formation of polymer biodeg-
radation products occurs at a very slow rate, and hence does not affect the normal
cell cycle. Thus, these polymers are biocompatible, biodegradable, and considered
safe [149] .