Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 392

�.2.1.�.2 Denaturation at �nterfaces and Adsorption
Denaturation may be defined as separation of proteins into independent strands or
rupture of the tertiary structure due to breakage of disulfide linkages, ultimately
resulting in loss of therapeutic/physiological activity of proteins. Mechanical or
thermal stresses lead primarily to protein denaturation. This phenomenon largely
depends upon temperature, pH, mechanical agitation, and salt concentration of the
bulk phase in which proteins are present [22] .
8.3 New Drug Delivery Systems for Proteins and Peptides
Formulation of protein and peptide drugs, their route of administration, rate, and
overall pharmacokinetic profile in the body are pivotal factors in deciding the suc-
cess of protein drug delivery. Until the 1950s, the oral route of drug delivery was
the most preferred, along with transport by single-cell epithelial barriers. However,
these methods of protein delivery by such conventional principles were not entirely
successful, and there has been a demand for developing delivery systems that deliver
proteins and peptides in a pulsatile manner.
The literature reveals that there are many proteins and peptide analogs that show
better absorption profile when given in pulsatile systems. Hormones and similar
endogeneous substrates need intermittent rather than continuous delivery. Continuous
dosing of hormones generally induces downregulation of hormone receptors on the
target cells and thus eludes the usefulness of the hormonal therapy. Smart delivery
systems that release the drug on being triggered by external stimuli of a physical,
chemical, or biological nature is of great use in hormonal delivery as in the case of
insulin, contraceptives, and growth hormones [23] . Current research on delivery sys-
tems in this area focuses on nanoparticles, implants and hydrogel based systems that
exhibit responsiveness to external stimuli.
Pulsatile- and stimuli-responsive drug delivery systems are particularly useful in
delivering the release factors that control the synthesis and release of endogeneous
hormones. The pulsed or triggered delivery systems are studied to alter their rate of
drug delivery in response to biological endogeneous stimuli such as changes in a spe-
cific molecule, a magnetic or electric field, temperature, light, or mechanical forces.
Such systems are suitable for therapeutics that necessitates the intermittent release of
drugs in order to elicit better therapeutic response. Several types of drug delivery sys-
tems cause the external stimuli-mediated, pulsed, or triggered release of therapeutic
moieties; these mainly depend upon thermally, electrically, and magnetically induced
release. However, the area has still remained largely unexplored.
8.3.1 Stimuli-Induced Pulsatile/Triggered Release System
One of the characteristics of polymers is that they undergo phase transition with sig-
nificant changes in their physicochemical properties, for example, swelling. Taking
the advantage of this unique property of polymers, smart devices based on these tran-
sitional changes can be designed and used. Stimuli-mediated response leads to drug