Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 571

acrylamide- co -alkyl methacrylate) [poly (IPAAm- co -AMA)], a thermoresponsive
polymer when incorporated in hydrogel, can cause on-off regulation of drug release
[360,366] . Control of delivery by programmable pumps may also be considered for
an externally regulated system.
11.5.9.2 S�﻽f-R��﻽﻽at�d/C﻽os�d Loo� Syst�m
Preprogrammed pulsatile drug delivery systems are closed loop systems based on
the body's homeostasis feedback system and regulate the releases of many P/P. This
category represents biomolecule-sensitive hydrogels, types of biologically inspired
materials, which are able to respond to specific physiological stimuli, such as an
increase of glucose levels, pH of the bioenvironment, or the presence of special pro-
teins and/or enzymes. These systems can be manufactured in the form of fibers, gel,
sheets, or microparticles to fabricate scaffolds. In closed loop systems precise/timed
drug delivery can be accomplished by spontaneous hydrolysis (i.e., bulk and surface-
eroding systems) or enzymatic degradation of the polymer comprising the device.
Biodegradable polymers like PLGA, starch, polyanhydrides, and crosslinked hydro-
gels are used for closed loop system [369,370] .
Stimuli-responsive protein-imprinted polymers were prepared by Zhiyong Chen
et al. [371] by a combination of molecular imprinting and reversible stimuli-respon-
sive polymer, using N -isopropylacrylamide (NIPAAm) as the major monomer, and
methacrylic acid (MAA) and acrylamide (AAm) as functional comonomers, N , N -
methylenebisacrylamide (MBAAm) as a crosslinker, and lysozyme or cytochrome c
as the template. The group observed that the molecularly imprinted polymers (MIPs)
respond not only to external stimuli such as temperature and salt concentration, but
also to the corresponding template protein, with significant specific volume shrink-
ing. Table 11.12 summarizes exclusive work done in the field of pulsatile delivery of
P/P drugs using both open loop and closed loop concept.
11.5.10 Pumps
A well-designed pump that provides flexible input rate characteristics for various
proteins and peptide drugs is a worthy technology in the field of novel drug delivery
systems. Generally the driving force for such a type of pump is a pressure differ-
ence generated by various means like pressurizing a drug reservoir, osmotic effect, or
mechanical actuation.
These pumps are available as portable external pumps or implantable systems
[379,380] . An example of an external pump is a syringe pump (such as Autosyringe ® ),
which has been used for continuous subcutaneous insulin infusion (CSII) for several
years [381] .
For the purpose of this chapter, we are concerned with implantable pumps and
infusion syringes. The concept can be illustrated by the following examples:
1. Infusaid ® pump, which consists of a hollow disk made of titanium and is divided into two
chambers by a bellow. One compartment contains a propellant (fluorocarbon) that, under
the influence of body heat (37°C), pushes against the other compartment to push the drug