In 2005, the largest sectors of the market consisted of sustained release implants and transdermal drug delivery systems. The global market for drug delivery systems was $134.3B in 2008 and projected to increase to $196.4B in 2014. This market potential has provided the driving force behind the development of nanodelivery systems. Smaller systems can incorporate features or mechanisms that allow more precise control over the drug delivery rate, enable the patient or physician to actively start/modify/stop drug release in an interactive format, and provide ways to reach difficult to treat locations. These next generation targeted delivery systems offer the possibility that the drug can be delivered preferentially to a relatively inaccessible site, a specific tissue type, or simply to limit side effects due to systemic exposure.
Published on: Mar 3, 2016
Transcripts - Nanogate Implants
In 2005, the largest sectors of the market consisted of sustained release implants and transdermal
drug delivery systems. The global market for drug delivery systems was $134.3B in 2008 and
projected to increase to $196.4B in 2014. This market potential has provided the driving force
behind the development of nanodelivery systems.
Smaller systems can incorporate features or mechanisms that allow more precise control over the
drug delivery rate, enable the patient or physician to actively start/modify/stop drug release in an
interactive format, and provide ways to reach difficult to treat locations. These next generation
targeted delivery systems offer the possibility that the drug can be delivered preferentially to a
relatively inaccessible site, a specific tissue type, or simply to limit side effects due to systemic
A drug delivery device that includes a device for implantation into the body, the capsule further
contains a reservoir for containing substances such as therapeutic agent, at least one port
allowing the substance to diffuse from or otherwise exit the reservoir and Nano pore exit for
controlling the rate of diffusion of substances from exit port. For example The application of
microfabrication and MEMS (microelectromechanical systems) technologies have resulted in a
new class of oral delivery systems. Silicon nanoparticles having dimensions of 50 μm × 50 μm ×
2 μm, with 25 μm × 25 μm × 1 μm deep wells were designed for targeted oral drug delivery.
Implantable drug delivery systems can be placed into three categories
• Passive – a system where drug release is pre-determined by the materials, fabrication methods,
or drug formulation and cannot be controlled after implantation
• Active – a system where drug release is controlled after implantation using mechanical,
electrical, magnetic, laser or other means
Passive systems utilize diffusion, osmotic potential, or concentration gradients as their
driving forces, while active systems include mechanical pumping, electrolysis, and other
Passive Delivery Systems
1. Membrane Controlled Diffusion System
Diffusion controlled systems, in their simplest forms, rely on diffusion of drug out of or through
a polymer layer that may be nonporous or microporous. The rate determining step may be
diffusion through the membrane structure or transport of drug through the static aqueous
diffusion layer. For membrane controlled diffusion, the diffusion coefficient is dictated by the
size of the drug molecule and the pore size or space between the polymer chains. This
technology has been widely used for delivery from reservoir-based oral and transdermal systems
and has recently been adapted for implants. For example the Retisert® implant (approved in
2005) measures 3 mm × 2 mm × 5 mm and is the second generation Medidur™ technology.
2. Matrix Controlled Diffusion Systems
A subclass of diffusion controlled systems takes advantage of a combination of drug release from
a polymer matrix via porosity and polymer erosion. Oncology is a therapeutic area that has taken
advantage of passive, diffusion controlled implantable systems. Resorbable multi-reservoir
arrays made from poly (l-lactic acid) and/or PLGA were fabricated, where each reservoir was
covered with a bioerodible membrane cap comprised of varying ratios and molecular weights of
PLGA. The devices measured ~11.9 mm in diameter, were 480-560 μm thick, and contained
thirty six 120-130 nl reservoirs
FIG 1: Passive, matrix controlled drug delivery systems including a bioerodible PLGA implant
Others type of passive drug delivery Nano gate implants are Microchannel implants and osmotic pumps
Active Delivery Systems
1. Single Reservoir Active System
Pumps generally include a drug reservoir, an actuator, and one or more valves in order to
accurately control the delivery of small volumes of a drug in solution. They may operate by
manual actuation, electrolysis, piezoelectric actuation, resistive heating, magnetic actuation, or
by incorporation of reversible polymeric valves.
The simplest example of an active drug delivery pump is one that is actuated manually by
pressing on it with an instrument or a finger. Such a system was designed for the treatment of
glaucoma, age-related macular degeneration, and diabetic retinopathy. The pump is fabricated
from three layers of polymethylsiloxane (PDMS) using soft lithography. The device was sutured
to the outside of the eye and contained a drug reservoir of approximately 200 μl, a check valve,
and a cannula (10 mm × 1 mm × 1 mm) placed through the wall of the eye. When the pump was
manually actuated by pressing on the drug reservoir, the increase in pressure in the reservoir
caused the check valve in the cannula to open, dispensing the drug.
Fig 2: Manually actuated drug delivery pump for ophthalmic use
2. Multi-Reservoir Active Systems
The advantage of one active delivery mechanism versus another, and the need for more than one
drug reservoir, is highly dependent on the treatment modality of the specific disease state and the
preferred delivery profile. Active delivery from multi-reservoir array implants can be actuated by
electrochemical, electro thermal, or laser means.
The knowledge and tools enabling the development of reservoir-based drug delivery systems
utilizing nanotechnology have come from number of diverse fields of study including chemistry,
materials science, mechanics, information technology, and microelectronics. The innovations at
the core of such novel oral, dermal, and implantable delivery systems come from the intersection
of these disparate fields. Devices combining reservoirs and nanotechnology driven by passive or
active mechanisms are enabling the delivery of both small and macromolecule drugs with
increased specificity and control. While tremendous progress continues on the development of
micro and nanotechnology for reservoir-based drug delivery devices, much additional work will
be required to translate the promising technology into safe and effective, well-controlled, patient
3. Book therapeutics micro/Nano technology by Mauro Ferrari
4. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology Cynthia L.
Stevensona, John T. Santini Jr.a,*, and Robert Langerb
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Electrothermally activated microchips for implantable drug delivery and
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