Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 589

and excipients) [515,516] , lipid composition [517] , process parameters, and drug-
lipid interactions, all impact on the rate of drug release from the DepoFoam parti-
cles. Biocompatibility of the formulation components is also an important factor for
a parenteral dosage system. Lipids used in the manufacturing DepoFoam particles
are synthetic versions of naturally occurring lipids and are, therefore, biocompatible.
DepoFoam particle itself does not cause any local or systemic toxicity in humans or
animals, and there is no “foreign body response” at the injection site after subcutane-
ous injections [518] . DepoFoam technology may therefore provide a unique solution
for controlled delivery of therapeutic proteins and peptides [519] .
DepoFoam formulations of a protein such as insulin, and peptides such as INF-
2b [520] insulin-like growth factor-1 (IGF-1) [521] , apolipoprotein E peptidomi-
metic [522] , cytarabin [523] , myelopoietin [524] , INF- [525] , progenipoietin [526] ,
leuprolide, enkephalin, and octreotide have been developed and characterized.
The DepoFoam system is capable of efficiently encapsulating therapeutic proteins
and peptides and effectively providing controlled delivery of these biologically active
macromolecules, which is illustrated by the above-mentioned examples of proteins
and peptides in the DepoFoam system. DepoFoam technology can also be extended
to other therapeutic macromolecules [527] .
11.7 Conclusion
P/P drugs are currently administered almost exclusively by the parenteral route.
However, physicochemical and pharmacokinetics parameters of P/P, like short half-
life, plasma protein binding, susceptibility to various degradation in the bioenviron-
ment and during processing like proteolysis and oxidation, and other stability-related
problems require attention when designing suitable delivery systems for P/P drugs.
Development of parenteral controlled release particulate systems offers much prom-
ise. Polymers are an integral part of many of these systems. For use in the body, these
polymers must be biocompatible and preferably biodegradable. Some of the more
promising delivery systems include oil-based injections, hydrogels, implants, lipo-
somes, nanoparticles, microspheres, and pulsatile delivery systems. Also, pegylated
proteins and protein crystals can provide controlled release and protection to the
P/P drugs. Pulsatile delivery systems may be externally regulated or self-regulated,
and such systems are desirable for P/P drugs as they reduce side effects related to
P/P therapy. PFSs and needle-free injections provide added convenience to paren-
teral delivery of proteins. CPPs are a promising approach for intracellular delivery of
P/P drugs. Overall, particulate systems are promising drug delivery systems for the
parenteral delivery of proteins. Nevertheless, optimization of formulation to protect
proteins even further against the stress effects of preparation and storage, as well as
studies of the activity of the released protein, both in vitro and in vivo , are required.
Additionally, further development of techniques for exploring the structural changes
of proteins after incorporation into drug delivery systems is needed in order to better
understand the potential destabilization mechanisms. Insight into these mechanisms
may aid in the preparation of a successful injectable drug delivery system for proteins.