Nanotechnology in

Drug Delivery System

MERVE YAMAN - 524517016
CHE7000 _ SEMINAR
AGENDA
Definitions
Evolution of Drug Delivery System
Nano Drug Delivery System – Route
Nano Drug Delivery System – Targeting
Polymeric Nano-Systems Used in Drug Delivery
DEFINITIONS
Nanotechnology: Science, engineering, and technology conducted at the nanoscale (1-100nm),
where unique phenomena enable novel applications.
Nanomedicine: The medical application of Nanotechnology
• Diagnosis, prevention and treatment of diseases
• Usage of nanoparticles to improve the behavior of drugs
Q:How do the Nanoparticles carry drugs?
Nanoparticles: Nanoparticles act as a vehicle on which the drugs are encapsulated within or
chemically bonded.
Drug Delivery Systems (DDS): are engineered technologies for the targeted delivery and/or
controlled release of therapeutic agents.
Evolution of Controlled DDS
Different structures of nanoparticles & their approx. sizes
They are in similar size range as biological nanostructures
Nano Drug Delivery System - Route
Q: How are Nanoparticles carrying drug administered into body?
Nano Drug Delivery System - Targeting
Q: How do the Nanoparticles deliver drugs to targeted tissues?

Purely Size & Geometry dependent mode

Normal blood vessels:
• Cell walls have tight junctions with spaces smaller than the
Nanoparticle
• Nanoparticle carrying drug is not able to enter, preventing
toxicity to normal tissues
Cancerous blood vessels:
• Cell walls are dilated with large gaps (200-1200nm) &
compromised lymphatic drainage
• Highly permeable for nanoparticles up to dia.400nm to enter
and preferentially accumulate at tumor sites.
Nano Drug Delivery System - Targeting
Not dependent on size or geometry
• Affinity ligands (e.g. antibodies,
DNA/RNA) are attached to Nanoparticle surface
• This allow the Nanoparticle carrying drug to recognize and
bind to target cells having specific receptors on their surfaces,
e.g. tumor cells
• After the nanoparticle is bound to the target cells, the drugs
carried within is released inside the target cells
Nano vs. Traditional Drug Delivery
Criteria Traditional
Specificity Drugs will pass through
unaffected sites before
reaching affected site
Dosage Release Higher initial dosage required
No control ability
Efficacy Drug concentration in affected
site is low
Side Effects Inevitable exposure of
unaffected sites to drugs
Nano
Delivered in more targeted
manner to the affected site
Able to control dosage by
trigger, requirement, and even
time-release
Drug concentration in affected
site is more optimized
Lesser exposure of unaffected
sites to drugs
Types of Nano-Sized Drug Delivery
Vehicles
• Nanosuspensions & Nanocrystals
• Liposomes
• Solid Lipid Nanoparticles

• Nanotubes & Nanowires

• Polymeric Nanoparticles
Polymeric Nano-Systems Used in Drug
Delivery
Benefits of Polymer Systems
Increase stability of volatile drug agents
Produced relatively easily
Vast source of chemistries available
May have engineered specificity both to the drug and the target – difficult to achieve with other carriers
Drug-release profiles and triggering dependent on polymer structure
Qualities of Relevant Polymers
Biodegradable/Biocompatible – lactic acid, glycolic acid, ethylene glycol, glycerin, fatty acids, amino
acids, sugars, etc.

Structure – mostly copolymers, combining different qualities of their parent polymers – Tg, Tm, crystal
structure, or exhibiting new ones - self-assembly
Most Common Types of Block
Copolymers
Typical Applications as:
- Micro and nano-particles
(mPEO-PLA, PLA)

- Unimolecular drug vehicles

(star blocks – PEG-PLA, PLA-PEG, dendr-PBE-PEO, etc.)

- Hydrogels
(Pluronics, PEO-PBO, PEG-PLGA, dendr-PBE-PEO, PIPAAm-PAA,
PEO-PLA)

- Micellar systems
(PEG-PLys, PEG-PAsp, PIPAAm-PBMA,etc.)

- Surface modifications
- Drug conjugates
Nanoparticles
In recent years, biodegradable polymeric nanoparticles have attracted considerable attention as potential
drug delivery devices in view of their applications in drug targeting to particular organs/tissues, as
carriers of DNA in gene therapy, and in their ability to deliver proteins, peptides and genes
through a per oral route of administration.
Benefits
- Fairly easy preparation
- Good control over size and size distribution
- Good protection of the encapsulated drug
- Longer clearance times

Drawbacks
- Extensive use of poly(vinyl alcohol)-PVA as PLA nanoparticles loaded with HAS
a detergent - issues with toxicity formed by a double emulsion
- Limited targeting abilities technique, stabilized with PVA
 Star Block Copolymers
Benefits
-Smaller sizes and lower intrinsic viscosities leading to better
excretion
- Size determined by chemical structure and uniform size
distribution
- Long clearance times due to slow degradation
- Possibility for attachment of homing (targeting) device at the
extremities
of the arms

Drawbacks
- Smaller loading capacity per molecule

- Longer preparation and purification process

Hydrogels
A hydrogel is a three-dimensional network of hydrophilic polymers that can swell in water and hold a large
amount of water while maintaining the structure due to chemical or physical cross-linking of individual
polymer chains.

Benefits
- Closest analogue to living tissue
- Capable of binding large amounts of fluids and drugs, incl. proteins
- Swelling ratio controllable by variation in structure (mostly by the hydrophobic/hydrophilic ratio)
- Small changes in temperature, pH, electric/magnetic field can trigger
large volume change/release of drug
- In many cases well defined release patterns
-
Drawbacks
- More difficult to characterize/predict behavior
- Not as well defined as stoichiometric compounds
Micellar Systems
In aqueous media, amphiphilic block copolymers, which have a large solubility difference
between the hydrophilic and hydrophobic segments, spontaneously form polymeric
micelles with a distinct core–shell structure in which a hydrophobic inner core is
surrounded by a hydrophilic shell
Benefits
- Unique core-shell structure
- Fairly high loading capacities depending on the chemistry of the drug
- Attachment of homing device(s) possible – biotin, folic acid, antibodies
- Variation of polymer composition, free charges, hydrophobic/hydrophilic ratio, offers vast possibilities for
design of uniquegene/protein/drug delivery vehicles
- Physical affinity targeting using stimuli-responsive polymers to pH, electro-magnetic fields, temperature
- Additional crosslinking in the core/shell leads to
novel nanostructures with different drug delivery properties
Drawbacks
- Difficult prediction of micellar characteristics by unimer structure
- Not very well studied
Miceller Systems
Surface Modification and Drug
Conjugation, Examples
Conclusions
• Polymeric systems have great potential in drug delivery applications
• Offer closest mimicking of natural products
• Difficult characterization, expensive and long processes of synthesis and purification are major
drawbacks
• Still none of the discussed systems is applied in practice to patients – FDA approval requires
extensive toxicity investigations
Thank you...