m.pharm (pharmaceutics) unit 2 rate controlled drug delivery system- mechanically activated drug delivery system

1. Mechanically
Activated Drug
Delivery System

2. Content
 Introduction
 Compression/tensile force- triggered drug delivery
 Shear- responsive systems
 Tension-responsive systems
 Ultrasound-activated drug delivery
 Magnetic force-triggered drug delivery

3. Introduction
 Mechanical force, with a sub classification of compressive, tensile, and
shear forces is ubiquitously achieved in the body or easily applied
externally.
 Force sources range from intrinsic compression/stretching via joint
movements to internal shear force in vascular systems, as well as exterior
acoustic and magnetic force remotely applied through the skin.

5.  In compression, a force is applied, resulting in an equal but opposing force along
the same axis, generally reducing the object's length along that direction.
 Similarly, an object under tension is pulled or stretched, lengthening the object
along the axis. This force, and resulting deformation, can be converted into
stress and strain.
 Instead of applying forces normal to the cross section, shear forces are applied
parallel to the object's cross section. Shear stress is similarly defined as the
parallel force divided by the cross sectional area acted upon; shear strain is the
strain in the parallel direction.
 The overall elastic material property is expressed by Young's modulus: E =
stress/strain.

6. Compressive/tensile force- triggered
drug delivery
 Compressive delivery systems require substrates that respond to and withstand
compressive loading.
 Commonly used materials for compression are elastomeric substrates.
Elastomers are viscoelastic polymer that is; they have viscous (resistance to
flow) and elastic properties (tendency to return to its original shape after
removal of stress) with time-dependent strain rate.
 Examples of elastomers in biomedical research include rubbers and silicones.
 As 3D-crosslinked polymer networks, hydrogels also withstand high
compressive forces, and thus act as effective compressive systems. Examples of
natural hydrogel polymers include alginate, chitosan, collagen, and hyaluronic
acid, whereas examples of synthetic hydrogel polymers include
poly(hydroxyethylmethacrylate), polyacrylamides.

7. o Elastomeric Deformation
Thermosensitive hydrogels have been extensively utilized for
controlled drug delivery. However, an external heat source is usually required
to activate the release.
Another example is multipurpose wearable elastomer that could
promote release of therapeutics to achieve elastic drug delivery. The
stretchable elastomer was integrated with microgel depots that contained
drug-loaded nanoparticles. The drug could be temporarily stored in the
depots. When stretching was applied, the drug could continuously diffuse
due to deformation of the microgels, which are attributed to enlarged
area for diffusion. Therefore, an on-demand drug delivery can be realized
convenient daily body motion.

8. o Mechanochemical Change
Mechanical-force induced chemical changes, including isomerization, ring
opening, chain scission and other intermolecular interactions can be useful
many biomedical applications, such as self-healing, actuators and sensors.

9. Shear- Responsive Systems
 Shear-mediated delivery relies on reversible material deformation or
disaggregation. Shear forces, present internally or externally, can trigger
release.
o Liposome Deformation
In response to high shear environments, liposomes can release their drug due
to lipid bilayer flexibility or when in contact with flowing fluids.

10. o Particle Aggregation and Dispersion
Microaggregates are capable of dispersing in response to shear stress,
offering another strategy for shear-responsive delivery. Nanoparticle
microaggregates composed of poly(lactic-co-glycolic) acid, are stable under
shear stresses commonly experienced by unobstructed coronary vessels.
Platelets, components in blood with a long circulation time, aggregate and
coagulate to cease bleeding during blood vessel injuries.
Once shear force increases, platelets sense this change and respond by
activating and adhering to the vascular wall at these narrowed sites. By the
physiological response of platelets inspired microscale aggregates of
nanoparticles to mimic platelets, which could remain intact in normal
physiological flow. However, they broke up into individual nanocomponents
once activated by high shear force and then adhered accumulated at
regions.

11. Tension- Responsive Systems
 It is an active area in the fields of sensors electronics and more recent drug
delivery. Each of the systems utilize soft and often elastomeric materials.
 In drug and protein delivery, tension is an ideal stimulus because of
ubiquity of tension in the dynamic nature of human body and increases
use of tension-driven medical devices.
 While most hydrogels are capable of compressive loading, hydrogels often
yield at low tensile strains. Biaxial stretching increases the surface area of
the hydrogel, allowing faster diffusion of substrate into the enzyme-
embedded hydrogel; an increase in surface area linearly correlates with
activity of both enzymes.

12. Ultrasound-Activated Drug Delivery
 Ultrasound is a sound wave with frequencies above 20 kHz. It can generate
longitudinal force/ pressure that induces mechanical force or/and local
heating in a noninvasive manner. Ultrasound has been widely used for
therapeutic purposes since the beginning of the 20th century including
tissue ablation, kidney stone shattering, imaging, liposuction, and
transdermal drug delivery. Ultrasonic waves can map the location and
promote drug release from carriers by causing localized hyperthermia,
acoustic cavitation, or/and acoustic radiation forces as designed. The
acoustic force can change the permeability or absorption of tissues and
"push" the drug into the cells or across the tissue.

13. Magnetic Force- Triggered drug
delivery
 Unlike ultrasound, the magnetic field remotely exerts force only on
magneto responsive materials. Currently, most magnetic materials are
inorganic matter, including super paramagnetic iron oxide or metals like
cobalt and nickel. However, these hard materials are limited for magnetic
force- triggered DDS.
 Researchers combine magnetic nanoparticles with a flexible polymer
material to achieve magneto responsive properties. By integration with
thermoresponsive materials, the localized heating caused by magnetic
particles under an alternating current magnetic field can be used to realize
controlled drug release. In an alternative way, the magnetic material
integrated with flexible polymers is able to deform by stretching,
compressing, or bending to release the drug on demand upon exposure to
a magnetic field.