Professional Documents
Culture Documents
693N
Materials Science Technologies for
Applications in Life Sciences
Self Assembly
MSE 693: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Self Assembly
• Self‐assembly is a term used to describe processes
in which a disordered system of pre‐existing
components forms an organized structure or
pattern as a consequence of specific, local
interactions among the components themselves,
without external direction
• Static and Dynamic self assembly
• Static: the ordered state forms as a system
approaches equilibrium, reducing its free energy
• Dynamic: called self organization
– Works on steady state principle
– Energy is required
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Advantages of Self Assembly
• Top down
– Lithography: UV limits, creation of masks and resist
– Electron beam lithography: slow, batch!
– Synthesis of new materials: SiO2
• Bottom up
– Molecular self assembly direct access to the nanometer
regime
– Inspired by nature: millions of years of evolution have
resulted in working molecular machines (enzymes)
• Designing molecular building blocks that spontaneously
assemble into defined, desired structures
• Challenge
– Assembly: assembly scheme must be embedded within the
inherent properties of the building block, making their design
a crucial step in the process
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Intermolecular Interactions and Molecular Recognition
• Self assembly
– Based on non‐covalent assembly of subuits to generate higher
ordered aggregates
– Offers efficient alternative to the classic covalent approach
– Requires fewer synthetic steps
– Results in higher yields
• Feasibility: rational design of simple building blocks that
are capable of selective and spontaneous assembly
• Design demands two key issues:
– What functionality will act as effective ‘glue’, and how will the
recognition features be incorporated and places into the
components to facilitate discriminating self‐assembly process
• Molecular recognition elements
• Molecular programming
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Intermolecular Interactions and Molecular Recognition
• Glue’ that are used to hold supramoleculer
architectures have been typically defined as
– Ionic, hydrogen, π‐π stacking, dispersion forces, co‐
ordination (dative) bonds or hydrophobic effects
• Supramolecular
– Well defined complex of molecules held together by
noncovalent bonds
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Self Assembled Monolayers (SAMs)
• Monolayer
– Layer that is a single molecule thick
• The formation of monolayers by spontaneous
chemisorption (chemical reaction between surface and
adsorbate) of long chain amphiphilic molecules at
surfaces results in creation of long range order
• Common to all SAMs
– Surface active head group that attaches to its corresponding
substrate via chemisorption process
• Results in monolayer with thickness dictated by length of
alkyl chain
• Factors contributing to the usefulness of SAMs
– Stability
– Functional group versatility
– Substrate monolayer composition
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Self Assembled Monolayers (SAMs)
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Organothiol Monolayers on Flat Gold Surfaces
• Assembly process is driven primarily by
attachment of the sulphur atom to the gold
surface
• Alkyl chains of the molecules organize
themselves laterally through van der Waals
interactions to form a densely packed monolayer
• Variety of functionalities can be incorporated
providing a versatile route to the assembly of
complex surfaces
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Organothiol Monolayers on Flat Gold Surfaces
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Organothiol Monolayers on Flat Gold Surfaces
• SAMs of alkanethiolates on gold can be prepared
either through a solution or vapour phase
adsorption process
• Kinetic studies on SAM formation show that
adsorption process is consistent with a first
order Langmuir isotherm where the growth rate
is proportional to the number of unoccupied
sites
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Organothiol Monolayers on Flat Gold Surfaces
• Sulphur atoms form a hexagonally packed
arrangement on the Au (111) surface
• The methylene groups tilt at an angle of 30°
from the surface normal to maximize the
favourable van der Waals interactions between
adjacent chains
• Densely packed, highly ordered
pseudocrystalline monolayers can be achieved
when alkyl chains are adequately long (n > 11)
• Packing density of SAM may be compromised if
functionalities other than methyl terminate the
monolayer
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Organothiol Monolayers on Flat Gold Surfaces
• SAMs in general tend to reject errors through a
self correcting mechanism during the
equilibrium process leading to their formation
• Defects arise due to
– Imperfections on the surface
– SAM preparation conditions
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Creating Nanostructured Materials and Patterned Surfaces
Microcontact printing
• Elastomeric polydimethylsiloxane (PDMS) stamp
is loaded with ‘ink’, typically a solution of
alkanethiol molecules and are then simply
transferred to the ‘paper’ typically gold surface
• A different SAM can then be introduced into the
underivatized regions after the initial pattern is
created or the gold underneath the
underivatized regions of the SAM can be etched
employing a chemical etching exposure
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Creating Nanostructured Materials and Patterned Surfaces
Microcontact printing
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Creating Nanostructured Materials and Patterned Surfaces
Microcontact printing
• Microcontact printing advantages
– Simple
– Rapid
– Inexpensive way to create multiple copies of SAM
– Time consuming and expensive lithographic
techniques are used only to create the master, and
the PDMS stamp can be used multiple times before
pattern degradation occurs
• Microcontact printing limitations
– Poor edge resolution and number of defect sites in
the created SAMs
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Creating Nanostructured Materials and Patterned Surfaces
Dip Pen Nanolithography
• Uses the tip of atomic force microscope (AFM)
as a pen to transfer the alkanethiol ink through
capillary action to the underlying gold substrate
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Creating Nanostructured Materials and Patterned Surfaces
Dip Pen Nanolithography
• Can not be used for rapid pattern fabrication
compared with microcontact printing
(disadvantage)
• High resolution patterning (~10nm) (Advantage)
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Organosilicon Monolayers
• SAMs created from chemisorption of alkyl
silanes (RSiX3, R2SiX2, R3SiX) to hydroxylated
silica surfaces
– R: alkyl chain
– X: chloride or hydroxyl terminated alkyl chain
• Silanol: functional group in Si chemistry with the
connectivity Si—O—H
• SiO2 coated Si wafer soaked in 6:1:1 :: DI, H2O2,
HCL (v/v), 10 min 75 °C, rinse with DI and dry
under nitrogen stream results in surface
hydroxyl groups on native SiO2 layer
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Organosilicon Monolayers
• Carried out in vapour or solution phase
• Surface active head group (a silane) self assembles
on the substrate (silanol)
• Compared with gold SAMs not as high quality
monolayers
– Temperature and amount of water present during
assembly
• Monolayer molecules anchored via silanol linkage to
the substrate
– Monolayer molecules form polysiloxane network at the
substrate surface
• Organosilicon monolayers: Extremely robust due to
Si—O—Si bonds covalently connecting the
monolayer to the substrate and to itself
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Organosilicon Monolayers
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Layer by Layer (LbL) Self Assembly
• Definition: Building multiple layers of charged
materials, including particles, polymers and
small molecules through electrostatic interaction
• Application in
– Drug delivery
– Nanoelectronics
– Implant coating
– Tissue engineering
• LbL used in biomaterials in two ways
– Assemble ultrathin films in a bottom up way
– Encapsulate nanomaterials on micro/nanotemplates
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Methods for LbL Self Assembly
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Methods for LbL Self Assembly
• Solid support with positive charge is incubated in a
solution containing polyanions (~30 min)
• Solid support is rinsed with water (2‐3 times) to
remove excess free polyelectrolyte
• Support immersed in a solution of cationic
polyelectrolyte and a layer is adsorbed and washed
– Original positive surface is restored
• Steps repeated till film of desired thickness is
achieved
• More than two compounds can be used
– Alternate positive and negative charge
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Methods for LbL Self Assembly
• Resaturation of polyelectrolyte adsorption,
resulting in the alternation of the terminal
charge after every subsequent layer deposition
is crux of the method
• Multilayer films deposited from several mg/ml
concentration of polyelectrolyte
– Much higher than required to cover substrate or
previous layer
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Methods for LbL Self Assembly
• Major driving force
– Electrostatic interaction between two adjacent layers
• Also present
– Short range hydrophobic forces
– Specific interaction between molecules
– Hydrogen bonding
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Materials for LBL Self Assembly
Synthetic and natural polymers chosen
• Synthetic polymers
• Polycations: Linear or branched
– Poly(ethyleneimine) PEI
– Poly(dimethyldiallyl ammonium) PDDA
– Poly(allylamine) hydrochloride PAH
• Polyanions
– Sodium poly(styrenesulfonate) PSS
– Poly(acrylic acid) PAA
• Most of these polymers are strongly charged
– Used to form LbL films in wide range of pH
• Used as: substrate for cell adhesion or building
microcapsules for protein encapsulation
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Materials for LBL Self Assembly
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Materials for LBL Self Assembly
Synthetic and natural polymers chosen
• Natural polymers
• Advantage
– Biocompatible
– Biodegradable
– Water soluble (must for LbL assembly)
• Three major natural polymers
– Proteins and enzymes
• Albumin, glucose oxidase
– Polypeptides
• Polylysine, poly (aspartic acid)
– Polysaccharides
• Hyaluronan, heparin, carboxymethyl cellulose, chitosan
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Materials for LBL Self Assembly
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Characterization for LBL Self Assembly
Quartz Crystal Microbalance
• Mass sensing technique based on the
piezoelectric effect
• Used for time dependent control of adsorption
and monitoring of the assembly in situ
• Multilayered assemblies can be characterized by
QCM in two ways
– Find resonance frequency shift after drying the
sample and calculate total amount of mass using
Sauerbrey equation
– Continuously monitoring or resonator frequency
during the adsorption process
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Characterization for LBL Self Assembly
Quartz Crystal Microbalance
• For pure elastic mass added to the surface linear
Sauerbrey equation can be used
Δf: measured resonant frequency (Hz),
f: intrinsic crystal frequency
Δm: elastic mass change (g)
A: electrode area
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Characterization for LBL Self Assembly
Quartz Crystal Microbalance
• For pure elastic mass added to the surface linear
Sauerbrey equation can be used
Δf: measured resonant frequency (Hz),
f: intrinsic crystal frequency
Δm: elastic mass change (g)
A: electrode area (cm2)
ρq: density of quartz (2.65 g/cm3)
μ: shear modulus (2.95 × 1011 dyne/cm2)
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
• As biomaterials, ultrathin films have advantages
such as
– Molecular architecture
– Thickness
– Surface charge
– Biocompatibility
– Biodegradibility
• Desired physical/chemical properties can be
achieved by selecting appropriate
polyions/inorganic particles
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
Standard approach for film preparation
• Taking aqueous solution of polycation and
polyanion at concentration of 0.01mg/ml (1‐3
mg/ml) and adjusting pH in a way that both
polyions are ionized
• Preparing a substrate of interest carrying a surface
charge
• Carrying out alternate immersion of the substrate in
polyion solution for 30 min with 1 min intermediate
water washing
– To wash a sample pH is maintained to keep polyions
ionized
• Drying the sample
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
• Applications ofLbL self‐assembled thin films as
biomaterials special interest lies in their
– Biocompatibility
– Biodegradability
• Used in
– Designing better films for medical implants and in tissue
engineering
– Constructing polyelectrolyte shells in microencapsulation
• Material selection is important for achieving
satisfying biocompatible interface
– Natural polymers
– Synthetic polymers
• Outermost layer largely decides the biocompatibility
of a film
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
• Judging the biocompatibility of a multilayered film
depends on
– Physiological environment
– Duration of tissue‐material contact etcetera
• In vitro environments
– Simple
– Time frame is less
• In vivo
– More complicated
– May involve systemic immune response
• In vivo tests can be employed to test LbL composite
film
– Hemocompatibility, carcinogenicity, immune responses
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
Ultrathin Coatings on Medical Implants
• Surface topography and chemistry of biomaterial
influence
– Protein adsorption
– Cell interaction
– Host response
• Interface between biomaterial and host is important
• Long term use of implant can be interfered by
– Local nonspecific protein adsorption
– Inflammation
– Infection
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
Ultrathin Coatings on Medical Implants
• Rationale behind surface modification
– Retain key physical properties while modifying only the
outermost surface to influence biointeraction
• Goal is building interface to
– Improve biocompatibility
– Reduce tissue implant reaction
– Prolong the lifetime of a device
Rule of thumb
• Nonspecific adsorption of proteins should be
minimized
• Beneficial molecules should become selectively
adsorbed onto biomaterials
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
Ultrathin Coatings on Medical Implants
• Advantages
– Broad selection of materials
– Precise control over coating thickness within
nanometer range with designed film structure
– No necessity of surface pretreatment in some cases
• Ideally, alteration of only the outer most
molecular layer (3‐10 Å) is sufficient
– Thicker films required to ensure full coverage on
medical implant
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
Ultrathin Coatings on Medical Implants
• Modification of medical devices and implants
include contact lens and vascular stents
• Stent implantation
– Treatment of occlusive blood vessel diseases with
the reduction of restenosis (repeat narrowing of
coronary artery)
• Restenosis: reoccurrence of stenosis, a narrowing of a
blood vessel, leading to restricted blood flow
– Stent implantation associated problems
– LBL assembly to improve stent properties
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Terms
• Restenosis: reoccurrence of stenosis, a narrowing of
a blood vessel, leading to restricted blood flow
• SMCs: Smooth Muscle Cells
• Glycosaminoglycans: are long unbranched
polysaccharides consisting of a repeating
disaccharide unit
• Hyperplasia: proliferation of cells within an organ or
tissue beyond that which is ordinarily seen.
Hyperplasia may result in the gross enlargement of
an organ and the term is sometimes mixed with
benign neoplasia/ benign tumor
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
• Atherosclerosis
http://www.nhlbi.nih.gov/health/health-topics/topics/atherosclerosis/
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
• Atherosclerosis: Narrowing and Hardening
*Condition in which an artery wall thickens as a result of
the accumulation of fatty materials such as cholesterol.
It is a syndrome affecting arterial blood vessels, a
chronic inflammatory response in the walls of arteries,
caused largely by the accumulation of macrophage
white blood cells and promoted by low‐density
lipoproteins (LDL, plasma proteins that carry cholesterol
and triglycerides) without adequate removal of fats and
cholesterol from the macrophages by functional high‐
density lipoproteins (HDL). It is commonly referred to as
a hardening or furring of the arteries. It is caused by the
formation of multiple plaques within the arteries
*http://en.wikipedia.org/wiki/Atherosclerosis
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
• Atheroma
In pathology, an atheroma is an accumulation
and swelling in artery walls made up of
(mostly) macrophage cells, or debris, and
containing lipids (cholesterol and fatty acids),
calcium and a variable amount of fibrous
connective tissue.
http://www.diabetes-mellitus.org/
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
• Atheroma
– Core of lipid
– Cholestrol crystals
– Cells
• Macrophages
• Smooth muscle cells
• Foam cells
– Necrotic debris
– Protein and degenerating blood elements
http://www.diabetes-mellitus.org/
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
• Percutaneous transluminal coronary
angioplasty (PTCA)
http://www.cardiology.md/procedures.htm
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
Coronary angioplasty
• Short term failure
– Elastic recoil of vessel wall
– Acute thrombosis at the site of angioplasty
– Acute dissection
• Long term
– Restenosis
• Stents are better than angioplasty alone
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
http://www.youtube.com/watch?v=2VvrIg94o64
http://www.youtube.com/watch?v=S9AqBd4RExk
http://www.youtube.com/watch?v=fmlHydYGQBQ
http://www.diabetes-mellitus.org/
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
• Percutaneous transluminal coronary
angioplasty (PTCA)
http://www.cardiology.md/procedures.htm
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
• Provide scaffold to support disrupted vascular
wall
• Minimize thrombus formation
Material
• Balloon expandable 316L SS or nitinol mesh
tubes
Issues:
• Subacute thrombosis (7‐10 days)
– Medicines
• Multidrug treatment with antiplatelet agents
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
Issues: Long term: in‐stent restenosis (< 6 months)
• Early damage to endothelial lining and stretching of vessel
wall
– Adherence and accumulation of leukocytes (WBC) and
platelets
• Wires embedded by smooth muscle cells (SMCs) in
collagen matrix
• Tissue thickening due to
– Release of growth factors, chemotactic factors and
inflammatory mediators
• Tissue thickening results in
– Increase migration and proliferation of SMCs
– Increase production of extracellular matrix molecules
– Narrowing of lumen and resulting in restenosis
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
In‐stent restenosis remedy:
Intracoronary radiotherapy using β or γ rays
• Block cell proliferation
• Induce cell death
• Inhibit migration of SMCs
• Issues:
– Late thrombosis
– Increases restenosis at the edge of the treated
field
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
In‐stent restenosis remedy:
Polymer coated drug eluting drugs
• Rapamycin
– Immunosuppression in solid organ transplant
– Inhibit proliferation, migration and growth of SMCs
and ECM synthesis
• Paclitaxel
– Anticancer drug
– Anti SMCs activity
Multilayered Biofilms Through LbL Self Assembly
Stents and Grafts
In‐stent restenosis remedy:
Polymer coated drug eluting drugs
• Drugs embedded in polymer matrix that is
coated onto the stent
• Drug released by diffusion or polymer
degradation
• Good for more than two years
Polyelectrolyte Encapsulation for Drug Delivery
• Advanced drug delivery systems
– Less administration frequency
– Fewer side effects
– High drug concentration at pathological sites
– Longer drug bioavailability
• Active drug delivery through encapsulation of drug
inside carriers
– Biodegradable and Biocompatible
• Major disadvantage: chlorinated solvents used in
fabrication
– Lead to organic residues in the system and damage
encapsulated materials such as proteins
– Incomplete and poorly controlled release
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Polyelectrolyte Encapsulation for Drug Delivery
• Layer by layer assembly is recognized as an
alternative to solve drug delivery problems
• Polyelectrolyte shells present unique advantages
– Easy fabrication process
– No necessity of chlorinated organic solvents
– Fine control of permeability through membrane
thickness and shell wall pore size
– Broad selection of shell materials
– Shells can be switched between ‘open’ and ‘closed’
states for triggered release
MSE 693N: Materials Science Technologies for Applications in Life Sciences Instructor: Vivek Verma
Polyelectrolyte Encapsulation for Drug Delivery
• Release drug in controlled manner
Polyelectrolyte Encapsulation for Drug Delivery
• Release drug in controlled manner
• Need minimum drug concentration for
effectiveness
– Drug is metabolized and removed from the body
– How to maintain effective drug concentration
• High concentration: Side effects?
• Periodic intervals
– Patient forget
• Controlled release formulations
– Zero order system
Polyelectrolyte Encapsulation for Drug Delivery
• Controlled delivery
– Minimize frequency of dose
– Small drug spheres coated with soluble coating
• Variable thickness of coating
– Sustained release
– Depends on in vivo environment
• Varies from patient to patient
• Controlled release
– Does not depend on in vivo environment
• Release by reproducible and predictable kinetics
Polyelectrolyte Encapsulation for Drug Delivery
Polyelectrolyte Encapsulation for Drug Delivery
Diffusion controlled delivery systems
• Membrane controlled reservoir devices
• Monolithic devices
http://www.uweb.engr.washington.edu/research/tutorials/drugdelivery.html
Polyelectrolyte Encapsulation for Drug Delivery
Polyelectrolyte Encapsulation for Drug Delivery
• Methods of encapsulation
– Direct coating of oppositely charged polyelecxtrolytes onto
drug micro/nano particles
– Loading of drug molecules into hollow polyelectrolyte
capsules
• Lyophilisation (Freeze Drying) is often used o stabilized
pharmaceutical products
– Freeze Drying: is a dehydration process typically used to
preserve a perishable material or make the material more
convenient for transport
– Freezing the material and then reducing the surrounding
pressure and adding enough heat to allow the frozen water in
the material to sublime directly from the solid phase to the
gas phase
Polyelectrolyte Encapsulation for Drug Delivery
• Freeze Drying
– Substance can be stored for long time (up to years) at room
temperature
– Greatly reduced water content inhibits the action of
microorganisms and enzymes
– Causes less damage to the substance than other dehydration
methods using higher temperatures
– Does not cause shrinkage or toughening of the material being
dried
– Flavors, smells and nutritional content generally remain
unchanged, making the process popular for preserving food
– Loss of other volatile compounds such as acetic acid (vinegar)
and alcohols can yield undesirable results
Polyelectrolyte Encapsulation for Drug Delivery
• Loading biomacromolecules into hollow
polyelectrolyte shells
• Protein drugs are major branch but formulation
technology is not very advanced
– Increasing gap between high therapeutic efficiency
demands is getting wider
Polyelectrolyte Encapsulation for Drug Delivery
• Monoclonal antibodies
– Monospecific antibodies that are the same
• They are made by one type of immune cell which are all clones of a
unique parent cell
– It is possible to create monoclonal antibodies that specifically
bind to almost any substance for detection and purification
• Cytokines
– Substances that are secreted by specific cells of the immune
system which carry signals locally between cells, and thus
have an effect on other cells
• Hormones
• Growth factors
– Naturally occurring substance capable of stimulating cellular
growth
• Enzymes
Polyelectrolyte Encapsulation for Drug Delivery
Loading Biomacromolecules into Hollow PE Shells
• Challenges in protein delivery
– Marginal stability of proteins
– Possess secondary, tertiary and, in some cases,
quaternary structures with labile bonds and side
chains with chemically reactive groups
– Structures can easily modified and even destructed
• Storing and delivering of proteins to target
tissues without loss of their function
Polyelectrolyte Encapsulation for Drug Delivery
Loading Biomacromolecules into Hollow PE Shells
• Multilayerd polyelectrolyte film adsorbed on
surface
• Core removed by short term exposure to acids
• Capsules
– Monodisperse in size
– Serve as permeable barrier
• Shells
– Ligand, enzymes and inorganic nanoparticles can be
assembled on surface for bioreaction and targeting
– Potential candidate for drug/DNA delivery and may be
applied for biosensing when loaded with molecular
probes
Polyelectrolyte Encapsulation for Drug Delivery
Loading Biomacromolecules into Hollow PE Shells
• Shell
– Interior is aqueous, similar to liposomes and polymer
vesicle
• Hydrophilic materials are ideal for loading
– Core is ideal for hydrophobic drugs
Polyelectrolyte Encapsulation for Drug Delivery
Loading Biomacromolecules into Hollow PE Shells
Advantages of hollow polyelectrolyte shells
• Capsule diameter can be varied (~10s nm to 10s um)
• Wide range of sacrificial template materials available
• Polymers, inorganic nanopartibles, lipids and proteins can
be used as shell wall material
• Shell interior environment (e.g., pH) can be adjusted
different from outside
• Shell wall permeability can be controlled by shell
materials and shell thickness
• Engineered shells can be responsive to external signals
such as low‐frequency alternating magnetic field for
triggered release of loaded materials
Polyelectrolyte Encapsulation for Drug Delivery
Loading Biomacromolecules into Hollow PE Shells
• Several proteins have been studied for
excapsulation by layer by layer mechanism
– Bovine serum albumin (BSA), insulin, oligonucleotide
• Open and close under changes of
– Environmental pH
– Temperature
– Solvent
– Magnetic field
• Close state should be close to physiological
conditions
– Proteins stay for long time without leakage
Polyelectrolyte Encapsulation for Drug Delivery
Loading Biomacromolecules into Hollow PE Shells
• Proteins can be triggered passively by
pathological conditions or actively by external
signals
– Proteins at tumor site can be triggered passively by
change in pH
Polyelectrolyte Encapsulation for Drug Delivery
Responsive “smart” systems
• Environmentally responsive systems
Mechano-chemical device for triggered release of drug. (a) The network consisting
of an environmentally responsive microgel is loaded with drug (D) and condensed
by a slight reduction in pH. (b) By coating the condensed microgel with a lipid
bilayer, the condensed state of the gel particle is stabilized in a solution that would
otherwise cause it to swell and release its drug content. (c) Due to the creation of
a single pore in the bilayer, the microgel undergoes a phase transition in a swelling
solution. The microgel swells, mechanically disrupting the bilayer coating and
causing a burst release of drug driven by ion exchange with physiological sodium
http://www.sciencedirect.com/science/article/pii/S0168365900002364