PRESENTATION ON

“Route of administration of
biotech product: parenteral
route mentioning
particulate carrier system
and
soluble carrier system.”
BIOTECH PRODUCTS

Biotechnology products are product which are manipulating and

modifying by organisms, usually at molecular level.
Biotechnology products in medicine are manufactured by using
recombinant DNA technology, which entails genetic
manipulation of cells, or a monoclonal antibody.
Examples of biotech product:
Acetone
Biohydrogen
Biopolymer
Biohydrogen
Biopolymer
Polyamide
 ROUTE OF ADMINISTRATION OF
BIOTECH PRODUCT:
Routes of administration of biotech
products are:

 Oral route.
 Parenteral route.
 Nasal route.
 Transmucosal route.
PARENTERAL ROUTE
 Parenteral mode of delivery has
been the major route of choice
for proteins and peptides, owing
to their poor absorption and
metabolic instability when given
by other alternative routes.

 Potent nature of these peptides/

proteins demands their targeting
to specific receptors to improve
therapeutic index of a drug.
PARENTERAL DRUG DELIVERY SYSTEMS:

 These systems include those intended for IV,

IM, intra-arterial, subcutaneous,
intraperitoneal and intrathecal use.
 The drug carrier systems used for defined
and controlled delivery of drug through this
route can be:

1. Particulates
2. Soluble carriers (Macromolecules)
3. Others
 PARTICULATES

There are different types of particulate carrier

systems .These are:
 Microspheres
 Microcapsules
 Nanoparticles
 Aquasomes
 Liposomes
 Emulsions
 Cellular carriers
 Replication defective viruses.
MICROSPHERES
 Microspheres are solid
particles in the particle size
range of few tenths of a
micrometer up to several
hundreds micrometer .They
contain dispersed drug in
either solution or
microcrystalline form. They
are prepared by various
polymerization and
encapsulation processes.
An example is targeting of
microspheres to the RES (1-7µm
particles) and to the lung
capillaries (7-12 µm particles).
The microspheres conjugating
receptor specific moieties, such
as monoclonal antibodies
incorporating magnetic
particles, or based on a
combination of two could be
used for active peptide(s) or
protein targeting.
The advantages of microspheres include:

Can be prepared cheaply if the correct encapsulation method

is optimized and chosen, and
Can be administered subcutaneously, IM or intraperitoneally
and thus implantation is not necessary.
Their disadvantages include:

 High molecular weight compounds have limited and restricted

loading and their release may be difficult,
 May successfully pass through biological barriers (like blood,
endothelium, RES) and cellular barriers before and they can be
effective.
 May be interact or complex with the blood components.
MICROCAPSULES
 Microcapsules carrier system
holds immense potential for
controlled release of
peptide moieties from
mammalian cells and
tissues.
 The microcapsules are
polymeric in nature and
prepared employing
interfacial polymerization,
or interfacial coacervate
phase separation of capsules
wall forming polymers.
 The capsule membrane
serves as a permeability
barrier. The polymers
conventionally used
include PVA, polyvinyl
acetate, nylon,
polyurethane, gelatin,
polyacrylonitrile etc.
 NANOPARTICLES
 Nanoparticles are very much similar to microspheres
but their particle size which is in the nanometer
range (10-1000nm).
 They can also be used for targeted delivery. Owing
to their small size they can pass through the
sinusoidal spaces in the bone-marrow and spleen.
 Targeting moieties like monoclonal antibodies can
be attached to Nanoparticles to enhance their
specificity.
 Polycyanoacrylate and glycolic acid co-lacted based
Nanoparticles have been discussed as an effective
adjuvant version that demonstrated effective
aduvanticity.
 The better adjuvanticity is attributed to the
effective presentation of antigens by Nanoparticles.
 The typical constitutive polymers include
cyanoacrylate, polymethacrylate, polystyrene poly
co-glyco-lactide, albumin and acrylic resins.
 The methods employed for preparation are
conventional solution, desolvation, in situ
micellar polymerization etc.
 AQUASOMES
 Aquasomes are self-assembling nanoconstructs
comprising of a solid ceramic core and a glassy
polyhydroxyl oligomeric surface coating.
 The system has been studied for the
immobilization of various bioactive molecules.
 These include insulin, antigen for Epstein-Barr
virus, HIV, Mussel adhesive protein, hemoglobin
etc.
 For example, aquasome-delivered insulin
showed 149.31-156.99 mg/dL fall in blood
glucose concentration.
 LIPOSOMES
 Liposomes are spherical vesicles formed when
phospholipids are allowed to hydrate in an
aqueous media. They consist of one or more
concentric bilayers surrounding aqueous phases.
 Protein and proteinaceous drug(s) are
incorporated in liposomes using dehydration
rehydration vesicle (DRV) and reverse phase
evaporation methods.
 The protein(s) bearing liposomes can further be
surface modified in order to endow them with
long circulatory character.
 PEG, pullulan coating, GM coating etc are used as
surface modifier.
The advantages of liposomes are:
 Flexible in size, shape and structure.

 Relatively nontoxic deposition.

 Ability to encapsulate both hydrophilic and lipophilic
peptide and proteins.
The drawbacks of liposomes are:
 The constituent phospholipids have an inherent
tendency to interact with peptides and proteins.
 Their capacity as adjuvants.
 EMULSIONS
 Colloid sized emulsion
droplets can be utilized for
parenteral delivery of
peptides.
 This delivery system can be
of great significance and
utility in protecting
hydrophilic or hydrophobic
drugs from direct contact
with body fluids and also in
delivering the drugs over a
prolonged period of time.
Advantages of emulsion
system:
 Large clinical acceptability.
 The amenability to large
scale production.

Disadvantage is of this
system:
 It is rather limited use but
investigations are in progress
to utilize their potential for
delivery of peptides.
 CELLULAR CARRIERS
 Enzymes and other
proteinaceous
pharmaceuticals can be
encapsulated in erythrocytes
to achieve a prolonged release
or targeting of the same.
 Some of the methods of
encapsulation include
hemolysis, dialysis and
electric field breakdown.
 The release of drug occurs by
simple diffusion or by a
specific transport system.
Advantages of erythrocytes include:

  Biodegradability.
 Non-immunogenicity.
 Large circulation life (up to 4 months).
 Easy availability.
 Large quantities of material can be entrapped in small volume of
cells (about 20-80%) extracellular concentration.
 Afford enzymatic and immunological protection.

Drawbacks include:

 Long term storage is problematic.

 Permeable to a large number of drugs.
 Only those drugs that are not susceptible to irreversible
denaturation under hypotonic conditions can be used.
 REPLICATION DEFECTIVE
VIRUSES
 Retroviral gene delivery
systems have been
developed to assist in entry
of genes into the cells. This
system consists of an RNA
copy of a gene package into
a viral particle.
 The basic concept of gene
therapy is that functionally
active genes are delivered
into the somatic cells of a
patient with genetic defect.
SOLUBLE CARRIERS (MACROMECULES)

Soluble carrier systems include :

 conjugates.
 chemically modified drugs and
 hybrid proteins.

The peptide/protein drugs can be conjugated with a

polymer/macromolecule.
Polymer modifications bring with it the
following changes:
 Masking of antigenic determinants.
 Masking of protease- susceptible sites.
 Masking of immunogenic recognition signals.
 Masking of clearance recognition signals.
 Allow free access to low molecular weight
substrates.
 Alter optimum pH by changing
microenvironment.
Protein molecules can themselves act as carriers for
targeting of other peptides/proteins.

The four basic mechanisms involved in targeting:

 Interaction with surface receptor.
 Facilitated uptake and interaction of intact
molecules with intracellular target site.
 Facilitated uptake and intracellular release of
warhead moiety.
 Facilitated uptake and release of a suicide
warhead, which is activated only after interacting
with its target.
Fig: Schematic representation of mechanisms for targeting peptide drugs.
 OTHERS
 On-demand systems
 Self-regulated system
 Temper sensitive systems
 Pumps

 Mechanical pumps
 Osmotic pumps
 Controlled- release micropumps
ON-DEMAND SYSTEMS

 It is beneficial to have externally

augmented delivery on-demand
as in delivery of insulin to patient
with diabetes mellitus.
 Magnetically modulated systems
have been designed to achieve
this end.
 The release rate is influence by
the position, orientation and
strength of the embedded
magnets , the amplitude and
frequency of the applied
magnetic field and the
mechanical properties of polymer
matrix .
 SELF-REGULATED SYSTEM
 The self-regulated systems are of great importance to deliver
insulin in response to blood glucose concentration for diabetic
patients.
 the pH of the microenvironment within the membrane is lowered
and the amine groups in the membrane are protonated, due to
this, the membrane swells and its permeability to the insulin
held in a continuous reservoir increases.
 TEMPERATURE SENSITIVE
SYSTEMS
 Some polymers like polyacrylamide derivatives
have inherent thermosensitive swelling behavior.
 This leads to a temperature-dependent release
pattern that can be exploited in pulsatile
delivery of peptides/proteins.
 PUMPS
 Mechanical pumps: Most of the portable pumps for
insulin delivery are syringe driven, either lead screw or
direct drive.
 Osmotic pumps: Osmotic pumps have been
used extensively for delivery of a large number
of preptides and protein drugs in animals. Some
of the representative examples include insulin,
ACTH, calcitonin, LHRH, growth hormone,
neutrotensin, vasopressin.
 Controlled- release micropumps: The
concentration difference between the drug reservoir and
the delivery site causes diffusion of the drug to the
delivery site to provide basal delivery.