Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 574

Figure 11.14 Schematic representation of osmotic pump consisting of osmotic agent, flow
moderator, piston, drug reservoir, membrane, and an orifice.
long as the osmotic pressure difference over the semipermeable membrane is constant. The
pump delivers a drug at a rate of 0.5-10 l/h, for 3 days to 4 weeks. A limitation of the sys-
tem is the fixed release rate, which is not desirable in all conditions [380] .
5. Viadur™, manufactured by Alza, a pump made for human use, delivers leuprolide for a
once-yearly implant for the palliative treatment of advanced prostate cancer. This is the
first product to use Alza's Duros ® implant technology and provides continuous, 12-month
suppression of testosterone with a single treatment. Viadur implant has an outside diameter
of 4 mm [209,380] .
Duros implant technology has developed catheterized Duros systems for intratu-
moral delivery or targeted delivery to the heart for continuous intrapericardial infu-
sion (e.g., Duros for delivery of growth factors to induce new blood vessel formation)
[209,384] . Pulsatile release can also be achieved by a programmed microinfusion
apparatus that can be implanted subcutaneously [385] .
Although continuous and pulsatile delivery of P/P drugs can be accomplished by
pumps, some crucial requirements like biocompatibility, no leakage, precise and safe
delivery, ease, remedy in case of failure, and easy monitoring must be fulfilled by the
pump before an actual therapeutic application.
11.6 New Advances in the Parenteral Administration of P/P
11.6.1 Pegylated Proteins
PEG has been found to be nontoxic and is approved by the FDA for use in drugs and
cosmetics [386] . PEGylation technology has been explored to enhance the clinical
effectiveness and controlled release of P/P drugs. It is a well-established technology
for extension of elimination half-life of P/P drugs.
PEG is a linear or branched neutral polyether of chemical formula HO-CH 2 -
(CH 2 -O-CH 2 -) n -CH 2 -OH, with functional groups at one or more termini to enable a
variety of conjugation possibilities. PEG is highly soluble in water and many organic
solvents. It is readily available in various sizes (molecular weights) and functional-
ized architectures (e.g., amino-, carboxyl-, sulfhydryl terminated). Various deriva-
tives of PEGs, such as PEG methyl melamide, PEG butyraledehyde, 6-arm PEG,
and so forth, are given in Table 11.13 . Molecular weight of PEG used in biomedi-
cal applications usually ranges between a few hundred and 20,000 Da [387] . Longer