Among drug carriers one can name soluble
polymers, microparticles made of insoluble or biodegradable, natural and
synthetic polymers, microcapsules, cells, cell ghosts, lipoproteins, liposomes,
and micelles. The carriers can be made slowly degradable, stimuli-reactive and
even targeted. Targeting is the ability to release the drug to the site of
interest
(See fig. 1)
FIGURE 1: TYPES OF DRUG DELIVERY
Any drug delivery system may be defined as a
system comprising of:
a) Drug
formulation
b) Medical device
or dosage form/technology to carry the drug inside the body
c) Mechanism for
the release
These systems can be described as controlled
drug release systems and targeted drug delivery systems.
The therapeutic benefits of these new systems
include:
·
Increased efficacy of
the drug
·
Site specific delivery
·
Decreased toxicity/side
effects
·
Increased convenience
·
Potential for prophylactic
applications
·
Better patient
compliance.
Various Drug Delivery Systems:
Carrier based Drug Delivery System:
A) Liposomes
B) Nanoparticles
C) Microspheres
D) Monoclonal antibodies
F) Resealed
erythrocytes as drug carriers
Trasdermal Drug Delivery Systems:
A) Sonophoresis
·
Mucoadhesive delivery
systems
·
Supramolecular delivery
systems
·
Variable release
delivery systems
B) Osmotic pump
C) Microencapsulation
Drug Delivery Carriers: Colloidal drug carrier systems such as micellar
solutions, vesicle and liquid crystal dispersions, as well as nanoparticle
dispersions consisting of small particles of 10–400 nm diameter show great
promise as drug delivery systems. When developing these formulations, the goal
is to obtain systems with optimized drug loading and release properties, long
shelf-life and low toxicity 2(see
fig. 2).
FIGURE 2: DIFFERENT PHARMACEUTICAL CARRIERS
Pharmaceutical Carriers: Micelles formed by self-assembly of amphiphilic
block copolymers (5-50 nm) in aqueous solutions are of great interest for drug
delivery applications. The drugs can be physically entrapped in the core of
block copolymer micelles and transported at concentrations that can exceed
their intrinsic water- solubility. Moreover, the hydrophilic blocks can form
hydrogen bonds with the aqueous surroundings and form a tight shell around the
micellar core. As a result, the contents of the hydrophobic core are
effectively protected against hydrolysis and enzymatic degradation. In
addition, the corona may prevent recognition by the reticuloendothelial system
and therefore preliminary elimination of the micelles from the bloodstream.
A final feature that makes amphiphilic block
copolymers attractive for drug delivery applications is the fact that their
chemical composition, total molecular weight and block length ratios can be
easily changed, which allows control of the size and morphology of the
micelles. Functionalization of block copolymers with crosslinkable groups can
increase the stability of the corresponding micelles and improve their temporal
control. Substitution of block copolymer micelles with specific ligands is a
very promising strategy to a broader range of sites of activity with a much
higher selectivity 3 (see fig. 3).
FIGURE 3: MECHANISM OF MICELLE FORMATION
Liposomes: Liposomes are a form of vesicles that consist
either of many, few or just one phospholipid bilayers. The polar character of
the liposomal core enables polar drug molecules to be encapsulated. Amphiphilic
and lipophilic molecules are solubilised within the phospholipid bilayer
according to their affinity towards the phospholipids. Participation of
nonionic surfactants instead of phospholipids in the bilayer formation results
in niosomes. Channel proteins can be incorporated without loss of their
activity within the hydrophobic domain of vesicle membranes, acting as a
size-selective filter, only allowing passive diffusion of small solutes such as
ions, nutrients and antibiotics.
Thus, drugs that are encapsulated in a
nanocage-functionalized with channel proteins are effectively protected from
premature degradation by proteolytic enzymes.
The drug molecule, however, is able to diffuse
through the channel, driven by the concentration difference between the
interior and the exterior of the nanocage 4 (see
fig. 4).
FIGURE 4: STRUCTURE OF LIPOSOME
Dendrimers are nanometer-sized, highly branched
and monodisperse macromolecules with symmetrical architecture. They consist of
a central core, branching units and terminal functional groups. The core
together with the internal units, determine the environment of the nanocavities
and consequently their solubilizing properties, whereas the external groups the
solubility and chemical behaviour of these polymers. Targeting effectiveness is
affected by attaching targeting ligands at the external surface of dendrimers,
while their stability and protection from the Mononuclear Phagocyte System
(MPS) is being achieved by functionalization of the dendrimers with
polyethylene glycol chains (PEG). Liquid Crystals combine the properties of
both liquid and solid states. They can be made to form different geometries,
with alternative polar and non-polar layers (i.e., a lamellar phase) where
aqueous drug solutions can be included.
TABLE 1: EXAMPLES OF PATENTS FOR LIPOSOMES
Patent No
Assignee/Inventors
Filed On
Title
US201002094925
SDG,Inc, Cleveland,OH
January 14,2010
Targeted Liposomal Drug Delivery System
US200702868986
Astellas Pharma Inc., Tokyo, JP
August 30,2005
Intracellular Drug Delivery Improving Liposome
US200701047777
Lau; John R; et al.
December 21, 2006
Targeted Liposomal Drug Delivery System
US200700148458
Zhang; Yuanpeng; et al.
June 30, 2006
Liposomal Delivery Vehicle For Hydrophobic Drugs
US200201822489
Daiichi Pharmaceuticals Co. Ltd.
August 29, 2001
Liposomes And Liposomal Dispersions
TABLE 2: SOME COMMERCIALLY AVAILABLE MARKETED
LIPOSOMAL BASED PRODUCTS 10
Trade Name
Trade Name
Manufacturer
Indication
AmBisome
Amphotericin B
NeXstar Pharmaceuticals
Systemic fungal infections
Abelcet
Amphotericin B
The Liposome Company
Systemic fungal infections
Amphotec
Amphotericin B
Sequus Pharmaceuticals
Systemic fungal infections
Doxil
Doxorubicin
Sequus Pharmaceuticals
Kaposi’s sarcoma
DaunoXome
Daunorubicin
NeXstar Pharmaceuticals
Kaposi’s sarcoma
Nanoparticles: Nanoparticles (including nanospheres and
nanocapsules of size 10-200nm) are in the solid state and are either amorphous
or crystalline. They are able to adsorb and/or encapsulate a drug, thus
protecting it against chemical and enzymatic degradation. In recent years,
biodegradable polymeric nanoparticles have attracted considerable attention as
potential drug delivery devices in view of their applications in the controlled
release of drugs, in targeting particular organ/or tissue, as carriers of DNA
in gene therapy, and in their abilities to deliver proteins peptides and genes
through peroral route 11.
Classification of nanomaterials :
A) Nanotubes-
They are hallow cylinders made of carbon atoms. They can also be filled and
sealed, forming test tubes or potential drug delivery devices.
B) Nanowires-
Glowing silica nano wire is wraped around a single stand of human hair. It
looks delicate. It is about five times smaller than virus applications for nano
wires include the early sensing of breast and ovarian malignancies.
C) Nanocantilever-
The honey comb mesh behind this tiny carbon cantilever is surface of fly’s eye.
Cantilevers are beams anchored at only one end. In nano world they function as
sensors ideal for detecting the presence of extremely small molecules in
biological fluid.
D) Nanoshells-
Nanoshells are hollow silica spheres covered with gold. Scientists can attach
antibodies to their surfaces enabling the shells to target certain shells such
as cancer cells. Nano shells one day also are filled with drug containing
polymers.
E) Quantum
dots- Quantum dots are miniscule semiconductor particles that can serve as
sign pots of certain type of cells or molecules in the body. They can do this
because they emit different wavelengths of radiations depending upon the type
of cadmium used in their cores. Cadmium sulphide for ultraviolet to blue,
cadmium selinide for most of the visible spectrum and cadmium telluride for far
infra red and near infra red.
F) Nano
pores- Nano pores have cancer research and treatment applications.
Engineered into particles, they are holes that are so tiny that DNA molecules
can pass through them one strand at a time allowing for highly precise and
efficient DNA sequencing. By engineering nanopores into surface of drug capsule
that are only slightly larger than medicines molecular structure, drug
manufacturers can also use nanopores to control rate of drug’s diffusion in
body.
G) Gold
nanoparticles- These nanoparticles seen in transmission electron micrograph
image, they have solid core. Researchs at north western university are using
gold particles to develop ultra sensitive detection systems for DNA and protein
markers associated with many forms of cancer including breast, prostate cancer.
H) Bucky balls-
Bucky ball is common for a molecule called buckminsterfullerene, which is made
of 60 carbon atoms formed in shape of hollow ball discovered in 1985. Bucky
balls and other fullerenes because of their chemistry and their unusual hollow
cage like shape extremely stable and can withstand high temperatures.
Applications- Bucky balls may see widespread use in future
products and applications, from drug delivery vehicles for cancer therapy to
ultra hard coating and military harmor.
Bucky ball- Antibody combination delivers
antitumor drugs.
·
Bucky balls to fight allergy.
·
Bucky balls as powerful antioxidants and also
inhibitor of HIV.
Demerits:
·
Bucky balls hurt cells.
·
Bucky balls have high potential to accumulate in
living tissue.
·
Difficulty of targeting drug delivery location.
Carbon nanotubes: Carbon nanotubes can be modified to circulate
well within the body. Such modifications can be accomplished with covalent or
non covalent bonding. Modifications can increase or decrease circulation time
within the body. Carbon nanotubes no significant toxicity when they have
modified so as to be soluble in aqueous body type fluids. They enter readily into the cells.
Cancer cells in tumor are larger than normal
cells and also exhibit leakage. Large molecules which circulate slowly can leak
into and accumulate in cancer cell. Carbon nanotubes carrying active agents
have been demonstrated in animal studies to do this. Researches have also used
carbon tubes to deliver the precursors of active drug which they call a
prodrug. eg: Cisplatin 12.
TABLE 3: EXAMPLES OF PATENTS FOR NANOPARTICLES
Patent No
Assignee/Inventors
Filed On
Title
US20100278920 13
University of South Florida, Tampa, FL
April 26, 2010
Polyacrylate Nanoparticle Drug Delivery
US20090155374 14
Sung; Hsing-Wen; et al.
January 15, 2009
Nanoparticle For Protein Drug Delivery
US20080095856 15
Jacobson; Gunilla B; et al.
May 14, 2007
Encapsulated Nanoparticle For Drug Delivery
US20080145439 16
Neurosystec Corporation, Valencia, CA
July 31, 2007
Nanoparticle Drug Formulation
Transdermal Drug Delivery System: Transdermal drug delivery is defined as self
contained, discrete dosage forms which, when applied to the intact skin,
deliver the drug, through the skin at controlled rate to the systemic
circulation. Transdermal drug delivery system (TDDS) established itself as an
integral part of novel drug delivery systems 28. Delivery
via the transdermal route is an interesting option because transdermal route is
convenient and safe.
The positive features of delivery drugs across
the skin to achieve systemic effects are:
·
Avoidance of first pass
metabolism
·
Avoidance of gastro
intestinal incompatibility
·
Predictable and extended duration of activity
·
Improving physiological
and pharmacological response
·
Termination of therapy is easy at any point of
time
·
Greater patient compliance due to elimination of
multiple dosing profile
·
Provide suitability for
self administration
·
Enhance therapeutic
efficacy29.
TABLE 7: EXAMPLES OF PATENTS FOR TRANSDERMAL
DRUG DELIVERY
Patent No
Assignee/Inventors
Filed On
Title
US20110190716 30
Easterbrook;Timothy J.et al.
June 2,2009
Transdermal Drug Delivery Device
US20110182949 31
Tang; Jiashang
May 29,2009
Stabilised Transdermal Drug Delivery System
US20100222751 32
Pharmapatch LLC San Diego, CA
September 22,2009
Transdermal Drug Delivery Patch
US20100143448 33
Koninklijke Philips Electronics N.V., Eindhoven,NL
September 26,2007
Multiple Nozzle Transdermal Drug Delivery System
TABLE 8: SOME COMMERCIALLY AVAILABLE MARKETED
TRANSDERMAL SYSTEMS- 10
Product name
Chemical
Developer/Marketer
Indication
Alora
Estradiol
TheraTech/Proctor and Gamble
Postmenopausal syndrome
Catapres-TTS
Clonidine
Alza/Boehinger Ingelheim
Hypertension
Deponit
Nitroglycerin
Schwarz-Pharma
Angina pectoris
Minitran
Nitroglycerin
3M Pharmaceuticals
Angina pectoris
Transderm-Scop
Scopolamine
Alza/Novartis
Motion sickness
Motion sickness
Estradiol
Noven Pharmaceuticals, Inc./ Novartis
Postmenopausal syndrome
Novel Drug Delivery System: In Herbal
Formulations: In the past few decades, considerable attention has been focused on the
development of novel drug delivery system (NDDS) for herbal drugs. The novel
carriers should ideally fulfill two prerequisites. Firstly, it should deliver
the drug at a rate directed by the needs of the body, over the period of
treatment. Secondly, it should channel the active entity of herbal drug to the
site of action. Conventional dosage forms including prolonged-release dosage
forms are unable to meet none of these.
The variety of novel herbal formulations like
polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions,
microsphere, transferosomes, and ethosomes has been reported using bioactive
and plant extracts 45.
TABLE 12: EXAMPLES OF HERBAL NDDS FORMULATIONS
FORMULATIONS
TYPE
OF NDDS
APPLICATION
BIOLOGICAL
ACTIVITY
Ampelopsin Liposomes46
Liposome
Increase efficiency
Anticancer
Paclitaxel Liposomes47
Liposome
High entrapment efficiency & pH sensitive
Anticancer
Colchicine Liposomes48
Liposome
Prolong drug release
Antigout
Artemisinin Nanocapsules49
Nanocapsule
Sustained drug release
Anticancer
Ginkgo biloba Nanoparticles50
Nanoparticles
Improve cerebral blood flow
Brain function activation
Hawthorn Phytosomes51
Phytosome
Increase therapeutic efficacy
& absorption
Cardioprotective
Quercetin Phytosomes52
Phytosome
Better therapeutic efficacy
Antioxidant
