Journal of Biomaterials and Nanobiotechnology, 2011, 2, 544-556
doi:10.4236/jbnb.2011.225065 Published Online December 2011 (http://www.scirp.org/journal/jbnb)
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug
Pramod Vishwanath Prasad1*, Anand Kumar2, Pramod Chandra Pal3, Radhey Shyam Sharma4,
Donthamsetty Nageswara Rao3, Tulsidas G. Shrivastav5, Ren-Shan Ge1
1Center for Biomedical Research, Population Council, The Rockefeller University, New York, USA; 2Department of Reproductive
Biology, All India Institute of Medical Sciences, New Delhi, India; 3Department of Biochemistry, All India Institute of Medical Sci-
ences, New Delhi, India; 4Division of RHN, Indian Council of Medical Research, New Delhi, India; 5Department of Reproductive
Biomedicine, National Institute of Health and Family Welfare, New Delhi, India.
E-mail: *email@example.com, *firstname.lastname@example.org
Received September 5th, 2011; revised October 14th, 2011; accepted November 20th, 2011.
Successful treatment of most of the diseases is limited by a lack of safe and effective methods of drug delivery. Drug
delivery methods have significant effects on the pharmacological efficacy of a drug. Every drug has an optimum con-
centration range within which maximum benefit is derived; and concentrations above or below the range can be toxic
or provide no therapeutic benefits at all. Therefore, development of an efficient drug delivery system remains an im-
portant challenge in medicine, and this can be achieved only through multidisciplinary approaches to the mechanisms
of delivery of drugs to targets in tissues. Thus, several drug delivery and drug targeting systems are currently being
developed. Targeting is an ability to direct the drug(s) to the desired site. There are two major mechanisms, viz., active
and passive for drug targeting. Controlled drug release and subsequent biodegradation are also indispensable for de-
veloping successful formulations. Colloidal drug vehicles such as micelles, vesicles, liquid crystal dispersions, and
nanomaterials consisting of miniscule nanoparticles of 5 - 200 nm diameter have shown great promise as drug delivery
systems. In this context, past decades have witnessed certain major advancements. This review article emphasizes on
these advances in the field of drug delivery systems.
Keywords: Drug Delivery Vehicles, Nanoparticles, Colloidosomes, Dendrimer s, Nanorobots
Drug delivery system is a process of administering
drug(s) to achieve its maximal therapeutic benefits in
humans or animals. The main objective of developing
new drug delivery systems is to promote the therapeutic
effects of a drug by 1) increasing drug’s bioavailability, 2)
preventing its toxic, harmful side-effects by increasing
the amount and persistence of a drug in the vicinity of
target cell and reducing the drug exposure of non-target
cells, and 3) minimizing drug degradation and loss [1-3].
Taking these challenges into account, various drug de-
livery and drug targeting systems are currently under
development. There are, however, some drug delivery
vehicles (carriers) viz., soluble polymers, micro- and
nano-particles made up of insoluble or biodegradable
natural and synthetic polymers, microcapsules, cells,
micelles, liposomes etc. have been developed. The carri-
ers can be made stimuli-reactive (for instance, pH- or
temperature-sensitive), slowly degradable, and targeted
(e.g., by coupling them with specific antibodies against
certain characteristic components of the area of interest).
Targeting is the ability to direct the drug-loaded system
to the site of interest. There are two mechanisms viz., 1)
passive and 2) active by which drug(s) are targeted (re-
leased) at the desired site(s). An example of passive tar-
geting is the preferential accumulation of chemothera-
peutic agents in solid tumors as a result of the enhanced
vascular permeability of tumor tissues compared with
healthy tissue; whereas active targeting involves the sur-
face functionalization of drug carriers with ligands that
are selectively recognized by receptors on the surface of
the cells of interest. Since ligand-receptor interactions
can be highly selective, this could allow a more precise
targeting of the site of interest.
Drug delivery systems are based on physical and bio-
chemical mechanisms. Physical mechanisms also re-
Bird’s Eye View on the Recent Advances in Drug Delivery Systems545
ferred as controlled drug delivery systems. It includes: 1)
desorption of adsorbed or surface-bound drug(s), 2) dif-
fusion through the carrier matrix, 3) diffusion (in the case
of nanocapsules) through the carrier wall, 4) carrier ma-
trix erosion, and 5) a combined erosion and diffusion
process. Biochemical mechanisms involve monoclonal
antibodies, gene therapy, vector systems, liposomes and
polymer drug adducts. Sustained or continuous drug de-
livery systems involve polymer(s) that release drug(s) at
a controlled rate due to diffusion out of the polymer(s) or
by degradation of the polymer(s) over time. Drug deliv-
ery systems exhibiting pulsatile release of drug(s) closely
mimics the way by which the body naturally produces
certain hormones like cortisol, insulin etc. It is achieved
by using drug-carrying polymers that respond to specific
stimuli (such as, changes in pH or temperature, exposure
to light etc). The mode of delivery can be the difference
between a drug’s success and failure, as the choice of a
medicine is often influenced by the way the drug is ad-
In recent years, the emergence of nanotechnology has
had a profound effect on many areas of healthcare and
scientific research. Scientists have known the potential
benefits of nanotechnology in providing remarkable im-
provements in drug delivery and drug targeting. Any
improvement in delivery techniques which minimize
toxicity and improve efficacy offers great potential bene-
fits to patients. Attempts are being made to better target
the drug and improve its effectiveness by 1) crossing
particular physical barriers, like the blood-brain barrier,
and 2) finding alternative and acceptable routes for the
delivery of protein drugs other than the gastro-intestinal
tract, where degradation can usually occur.
Pharmacological efficacy of any drug significantly
depends on the methods of its delivery. Every drug has
an optimum concentration range within which maximum
benefit is obtained, and concentrations above or below
the range can be harmful or provide no therapeutic bene-
fits. Therefore, determination of optimum dose of any
therapeutics and its efficient delivery to target tissues for
successfully treating diseases needs a multidisciplinary
approach. In this approach, several innovative and strate-
gic ideas on controlling the pharmacokinetics, pharma-
codynamics, non-specific toxicity, immunogenicity, bio-
recognition, and efficacy of drug(s) were generated and
utilized. As well, the combined approaches from various
disciplines viz., polymer science, pharmaceutics, bio-
conjugate chemistry, and molecular biology and highly
integrated efforts of biologists, chemists, nanotechnolo-
gists, biochemical- and biophysical-engineers resulted
into the development of several new drug delivery sys-
tems over the past decade. In the present review, an ex-
tensive effort has been made to bring them together on a
single platform, under following headings:
2. Drug Delivery Vehicles
Drug delivery vehicles are substances that serve as me-
chanisms to improve the delivery and the effectiveness of
drug(s). Vehicles are also used in designs to increase the
effectiveness of drug delivery to the target sites of phar-
macological actions. The aims of developing drug deliv-
ery vehicles are to obtain systems with optimized drug
loading and release properties, long shelf-life and low
toxicity. Some of the recently developed drug delivery
vehicles are briefed here.
1) Nanomaterials are hollow or solid structure, with
diameter in the 1 - 1000 nm range, and can be filled or
loaded with drugs and detection agents. Targeting moie-
ties can also be attached to their surface to make them
useful for targeted drug delivery. The nanomaterials in-
clude nanoparticles, lipid core micelles, polymeric mi-
celles, biodegradable polymeric nanoparticles, liposomes,
nanopores, nanospheres, nanocapsules, nanotubes, nano-
wires, nanoshells, nanocantilever, dendrimers, gold nano-
particles, protein nanoparticles, buckminsterfullerene
(commonly called bucky balls) and quantum dots. It must
be noted that all of the nanomaterials mentioned are
commonly termed as ‘nanoparticles’, depending on the
ease of user. However, nanoparticles include only solid
2) Nanoparticles are either amorphous or crystalline
solid. They are typically made up of a single material and
measure about 5 - 200 nm in size. They have the property
to absorb and (or) encapsulate drug(s), thus protecting
it(them) against chemical and enzymatic degradation.
They have emerged as potential drug delivery devices
because of their applications in the controlled release of
drugs . They have been particularly employed in tar-
geting particular tissues/organs as carriers of DNA in
gene-therapy, and in their ability to deliver proteins, pep-
tides, genes through oral route. Efforts for application of
protein nanoparticles in drug delivery are being made .
Superparamagnetic iron oxide nanoparticles (SPIONs)
are commonly produced by reduction of iron salts under
alkaline condition. They have proved to be promising
drug delivery vehicles for some biomedical applications
such as targeted drug delivery and imaging, hyperthermia,
magneto-transfections, gene therapy [6,7], stem cell
tracking, molecular/cellular tracking, magnetic separa-
tion technologies (e.g. rapid DNA sequencing), and de-
tection of liver and lymph node metastases. Most re-
cently, SPIONs have been successfully used for early
detection of inflammatory diseases, cancer, diabetes and
atherosclerosis . Currently, poly ethylene glycolpoly-
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug Delivery Systems
hedral oligosilsesquioxane (PEG-POSS) amphiphilic
nanoparticles are being investigated to encapsulate insu-
lin as new drug delivery vehicles. Insulin release tests
have indicated that insulin was well-protected inside
PEG-POSS nanoparticles at gastric pH for 2 hrs, and was
released at intestinal pH (pH 6 - 7) where the absorption
and activation of the drug are necessary. Therefore, such
nanostructured PEG-POSS nanoparticles seemed to be
useful as a potential carrier for oral insulin drug delivery
systems, in near future .
3) Lipid core micelles and polymeric micelles are
nanosized colloidal particles. Both of them are made up
of hydrophobic core and hydrophilic shell. They are suc-
cessfully used for the solubilization of various poorly
soluble drugs (particularly anticancer drugs) and demon-
strate attractive properties as drug carriers for targeted
drug delivery. Drug-loaded lipid-core micelles can spon-
taneously target body areas with compromised vascula-
ture (viz., tumors, infarcts) via the enhanced permeability
and retention (EPR) effect . Biodegradable polymeric
nanoparticles or microspheres are potential drug delivery
carriers of peptide and protein drugs and vaccines .
4) On contrary to the lipid core micelles and polymeric
micelles, liposomes are microscopic nanoparticles made
up of phospholipid bilayers surrounding an aqueous core.
The polar nature of liposomal core facilitates polar drug
moieties to be encapsulated. However, amphiphilic and
lipophilic drug moieties are also encapsulated by solubi-
lizing them within phospholipid bilayer . On the ba-
sis of size and lamellarity (number of bilayers present
within a liposome), liposomes are classified into three
types: small unilamellar vesicles (SUVs), large unilamel-
lar vesicles (LUVs), and multilamellar vesicles (MLVs).
Different types of liposomes are widely used for deliver-
ing certain vaccines, cancer treatment, and against infec-
tious diseases. Liposomes treat cancer by encapsulating
drugs, shielding healthy cells from drug’s toxicity and
prevent drug’s concentration in vulnerable tissues like
liver and kidneys. They also eliminate some side-effects
(like nausea, hair loss etc.) of cancer treatment. Moreover,
fusogenic liposomes have the potential to deliver drugs
intracellularly and therefore, markedly enhance therapeu-
tic activity [12-15].
5) Nanowires are nanoscale sensing wires. They can
be coated with molecules such as antibodies to bind to
proteins of choice and transmit their information through
sensing electrodes to the computers . They have ap-
plications in the early sensing of breast and ovarian ma-
lignancies. In the rapidly emerging field of nanoneuro-
sciences, nanowired drug delivery using Titanium diox-
ide (TiO2)-based nanowires (50 - 60 nm) tagged with
drugs have been found to enhance the neuroprotective
efficacy of drugs in spinal cord injury following trauma
[17,18]. Therefore, the use of nanowires as drug carriers
significantly enhances the delivery and therapeutic effi-
cacy of drug(s). Silicon nanowire-coated beads (i.e., nano-
wire coatings) paired with epithelial physiology have
shown significantly increased adhesion (almost 100-fold),
in mucosal conditions. Without these bioadhesive deliv-
ery devices, complex compounds were undergoing typi-
cal degradation and clearing from mucosal tissues by the
mucous layer . Currently, a novel hybrid nano-mate-
rials such as iron nanowires are being developed for use
in high thermal efficiency hyperthermia therapy .
6) Nanoshells are composite nanoparticles made up of
a hollow silica core (SiO2, semiconductor) surrounded by
a gold shell (Au). Silica-gold (SiO2-Au) nanoshells are
unique because their peak extinctions are very easily
tunable over a wide range of wavelengths, particularly in
the near infrared region (800 - 1200 nm) of the spectrum.
Light in this region is transmitted through tissue with
relatively little attenuation due to absorption. In addition,
irradiation of SiO2-Au nanoshells at their peak extinction
coefficient results in the conversion of light to heat en-
ergy that produces a local rise in temperature. This makes
nanoshell hot, consequently the heat kills the cancer cell.
Thus, to develop a photothermal modulated drug delivery
system, some groups of scientists have fabricated a non-
toxic hydrogel polymer network encapsulating silica-
gold (SiO2-Au) nanoshells. The hydrogel coatings can be
collapsed by exposure to light via excitation of the strong
Plasmon resonance of the silica-gold nanoshells; this
excitation provides a ready source of heat to the system.
Photothermally modulated drug delivery profiles for me-
thylene blue, insulin, and lysozyme have been achieved
by irradiation of the drug-loaded nanoshell-composite
hydrogels, which showed that drug release was depend-
ent upon the molecular weight of the therapeutic mole-
cule. Currently, these nanoparticles are further being de-
veloped as photothermally responsive drug-delivery ve-
hicles that undergo structural changes slightly above
physiological temperature [21-24]. Moreover, antibodies
can be attached to the surfaces of nanoshells, thus ena-
bling the shells to target certain cancer cells .
7) Nanotubes are hollow cylindrical tubes made up of
carbon atoms, with cross-sectional dimensions in the
nanometer range, and lengths can be extended over a
thousand times their diameters. They can be filled with
drug(s) and sealed and thus serve as potential drug deliv-
ery vehicles. Currently, Aluminium oxide nanotubes
have been fabricated and found to have many favorable
properties as drug carrier for controlled release of drug(s)
. It has potential for therapeutic surface coatings on
medical implants, as well. Nanotubes have been reported
as high-specificity sensors of antibody signatures of
autoimmune disease  and of single-nucleotide poly-
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug Delivery Systems547
morphisms (SNPs) [16,27].
8) Nanobots are nanotubes intercalated with anti-
cancer drug(s). They release drug(s) only near a tumor in
response to pH stimulus, since tumors and inflammated
places are typically more acidic (pH 6.5) than normal
tissues (pH 7.4) .
9) Nanoneedles are hollow, tubular or conical needles
in the nanometer size range. They are nontoxic, biode-
gradable and made up of eco-friendly materials silicon or
boron-nitride. Nanoneedles have central bore of suffi-
cient size to allow passage of molecules. They can be
mounted in arrays and used to deliver any drug or vacci-
nation antigen, straight through the cellular wall, either in
the cytoplasm, or inside the very nucleus of the cell. The
array is pressed against the skin. This may reduce the
volume of antigen required to ensure adequate immunity,
as well as creating multiple immune pathways. This sys-
tem was found to deliver insulin and diclofenac effec-
tively in the animal models . Due to non-invasive
penetration method, nanoneedles avoid pain sensation
during drug or vaccine delivery (that will engender
greater patient compliance). This simultaneously mini-
mizes vaccine or drug degradation and enhances bioa-
vailability. Nanoneedles serve as a powerful new tool for
a) quantitatively examining biological processes occur-
ring within a cell’s nucleus or cytoplasm; b) studying
biophysical properties at the molecular level inside living
cells. Combined with molecular targeting strategies using
quantum dots and magnetic nanoparticles as molecular
probes, the nanoneedle drug delivery method can poten-
tially enable the simultaneous observation and manipula-
tion of individual molecules [30,31]. In future, nanon-
eedles can also be used as electrochemical probes and as
optical biosensors to study cellular environments.
10) Nanorods are solid nanoneedles. They are also
made up of silicon or boron-nitride. They are useful in
light emitting diodes (LED), and laser diodes . They
have the potential to be used as drug delivery vehicles.
11) Nanocantilevers are made up of flexible beams of
carbon atoms. Their beams are anchored at only one end,
resembling a row of diving boards. The beams of nano-
cantilever deflect when the biomolecules of interest bind.
The deflections are either observed directly by laser light
or generate detectable shifts in the physical properties of
the beam, such as their resonant-vibration frequency.
Therefore, these biomolecular sensors have the ability to
“multiplex” massively—that is, to detect a large number
of different molecular species at the same time. Thus, the
nanocantilevers (like microcantilevers) are being devel-
oped for serum and tissue proteomics-based cancer di-
agnostics, prognostics and therapeutic-efficacy monitor-
12) Nanopo res are tiny holes engineered into particles.
The holes are engineered so tiny that DNA molecules can
pass through them one strand at a time, allowing for
highly precise and efficient DNA sequencing. Drug
manufacturers can engineer nanopores into the surface of
a drug capsule which are only slightly larger than the
medicine’s molecular size, thus controlling the rate of a
drug’s diffusion in the body. Currently, nanoporous sys-
tems engineered to mimic natural filtration systems are
actively being developed for use in smart implantable
drug delivery systems, bioartificial organs, and other
novel nano-enabled medical devices. Synthetic nanopor-
ous materials have numerous potential biological and
medical applications that involve sorting, sensing, isolat-
ing, and releasing biological molecules . Scientists
have used mesoporous thin silica films with nanopores as
anticancer drug carriers and gained mechanistic insights
into the feasibility of using such films for drug delivery
at the target-site . Thus, nanoporous systems have
applications in the cancer research and treatment.
13) Bucky balls (Fullerene) are common name given
to a recently discovered molecule called buckminster-
fullerene . Bucky ball is made up of 60 carbon atoms
arranged in a soccer ball-like structure. Unlike other
molecules that have applications as cancer drug delivery
vehicles, fullerenes do not break down in the body and
are excreted intact. This trait helps for some cancer
treatment compounds that are dangerous to healthy cells.
For example, fullerene drug delivery particles that con-
tain radioactive atoms would allow for the complete re-
moval of radiation from the body following treatment
. Bucky balls and other fullerenes because of their
chemistry and their unusual hollow, cage-like shape ex-
tremely stable and can withstand very high temperatures
and pressures. Bucky ball is the only molecule composed
of a single element to form a hollow spheroid which
gives the potential for filling it, and using it as novel drug
delivery systems. Bucky balls have some demerits like: it
hurts cells, have high potential to accumulate in living
tissues, and difficulty in targeting drug delivery site. But
it may find global use in future products and applications
a) drug delivery vehicles for antitumor drugs or cancer
b) to fight allergy,
c) as inhibitor of HIV, and
d) as powerful anti-oxidant, and
e) in ultra-hard coating in the military services.
14) Gold Nanoparticles are made up of solid cores of
Gold (Au). Scientists are using gold nanoparticles to de-
velop ultrasensitive detection systems for DNA diagnos-
tics, biosensors and protein markers associated with
many forms of cancer, including breast and prostate can-
cer . Colloidal gold nanoparticles represent a com-
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug Delivery Systems
pletely novel technology in the field of particle-based
tumor-targeted drug delivery. Recently, it has been suc-
cessfully used for targeted delivery of tumor necrosis
factor to treat a solid tumor growing in mice .
15) Quantum Dots are miniscule semiconductor na-
noparticles with an inert, non-toxic polymer coating. The
core material can be chosen depending on the emission
wavelength range being targeted. Targeting molecules
can be attached to the coating. They serve as sign posts
of certain types of cells or molecules in the body because
they emit different wavelengths of radiations depending
upon the type of Cadmium used in their cores. Cadmium
sulfide (CdS) for ultra violet to blue, Cadmium selinide
(CdSe) for most of the visible spectrum and Cadmium
telluride (CdTe) for far-infra red and near infra red.
Quantum dot bioconjugates with targeting antibodies
have been used to recognize molecular signatures in-
cluding ERBB2 [16,40,41]. Quantum dots are very stable
under complex in vivo conditions that make them suit-
able for advanced molecular and cellular imaging, drug
delivery and for highly sensitive bioassays and diagnos-
tics [42-45]. Advances in the quantum dot technology
can provide a great deal of information about the mo-
lecular events in tumor cells and early diagnosis of can-
16) Carbon nanotubes (CNT) are hollow nanostruc-
tures made up of carbon. They can be covalently or
non-covalently modified to circulate well within the body.
Such modifications can increase or decrease circulation
time with in the body. CNT can be functionalised with
bioactive peptides, proteins, nucleic acids and drugs, and
used to deliver their cargos to cells and organs. Because
functionalised CNT display non-significant toxicity and
are non-immunogenic, therefore, they hold great poten-
tial as drug delivery vehicles and have emerged as an
efficient nanovector for transporting and translocating
therapeutic molecules [46-48]. Scientists have used CNT
to deliver active agents, drugs in the animals. Carbon
nanotubes have been developed to seek and destroy tu-
mor cells .
17) Na norobots are capable of treatment, prophylaxis,
and diagnosis of certain ailments. They represent the next
generation of drug delivery devices [50-52]. Coming era
is most likely to see its usefulness in treating and diag-
nosing certain diseases.
18) Dendrimers are synthetic nanovectors (nanoparti-
cles) measuring about 5 - 10 nm in diameter. They are
made up of polymers with a central core. Dendrimers
render drug molecules a greater water-solubility, bioa-
vailability, and biocompatibility. They are hyperbranched
(like a tree) and monodisperse three-dimensional mole-
cules with defined molecular weights and have large
numbers of functional groups to which drugs (and other
molecules) can be attached. They have well-established
host-guest entrapment properties. As the dendrimers have
many different functional groups (sites), therefore drugs,
and other molecules like polyethylene glycol can be at-
tached. Polyethylene glycol attached to dendrimer pre-
vents the body’s immune system to detect it as foreign,
thereby slows the process of breakdown of “drug loaded
dendrimers”. This fascinating nanovector holds signifi-
cant promise for cancer diagnosis and treatment. Re-
cently, scientists have fashioned dendrimers into sophis-
ticated anticancer machines carrying five molecules as
five different tools: a) a molecule designed to bind to
cancer cells, b) second molecule that fluoresce upon lo-
cating genetic mutations, c) a third to assist in imaging
tumor shape using X-rays, d) a fourth carrying drugs
released on demand, and e) a fifth that would send a sig-
nal when cancerous cells are eventually dead. Therefore,
dendrimers have significant promise as delivery vehicles
for drugs, particularly, the non-steroidal anti-inflamma-
tory, anti-microbial/anti-viral and potent anti-cancer drugs.
A new generation of dendrimer-based delivery systems
will enable the efficient transport of drugs across cellular
19) Hydrogels are enviro-intelligent and stimuli-sen-
sitive three-dimensional gel systems . They are made
up of hydrophilic and polymeric networks capable of
imbibing large amounts of water or biological fluids. The
networks are composed of homopolymers or copolymers,
and are insoluble due to the presence of chemical
crosslinks (tie-points, junctions), or physical crosslinks,
such as crystallites or entanglements. Hydrogels exhibit a
thermodynamic compatibility with water, which allows
them to swell in aqueous media. They are used to regu-
late drug release in reservoir-based, controlled release
systems or as carriers in swellable and swelling-con-
trolled release devices. As they are stimuli-sensitive so
modulate release of drugs in response to electric field,
temperature, pH, ionic strength, and specific analyte
concentration differences. In these controlled drug deliv-
ery systems, release can be made to occur within specific
areas of the body (e.g., within a certain pH of the diges-
tive tract) or also via specific sites (adhesive or cell-re-
ceptor specific gels via tethered chains from the hydrogel
surface). Hydrogels as drug delivery systems can be very
promising materials if combined with the technique of
molecular imprinting (nanoscale templating). Chitosan is
a cationic polymer (polysaccharide). It is gaining impor-
tance in the development of mucoadhesive hydrogel-
based drug delivery system because of its good biocom-
patibility, biodegradability and non-toxic nature [56,57].
Pectin-based biodegradable hydrogels consist of pectin
and polyacrylonitrile, have exhibited a pH-responsive
swelling-deswelling behavior at pH’s 2 and 8. This on-
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug Delivery Systems549
off switching behavior provides the hydrogel with the
potential to serve as drug delivery vehicles . Poly-
meric biomaterial based hydrogels viz., gelatin (G) and
sodium alginate (SA) as base bio polymer(G/SA); or in
combination with seabuckthron oil (SB) i.e., G/SA/SB;
or polyvinylpyrrolidone (PVP) and carboxymethylcellu-
lose (CMC) i.e., PVP/CMC; or with boric acid (BA) i.e.,
PVP/CMC/BA have the ability to be used as a tool for
transdermal drug delivery .
20) Colloidosomes are made up of an aqueous or hy-
drogel core that is coated by a semi-permeable colloidal
shell. Among several methodologies of colloidosome
synthesis, it is generally performed by self-assembly of
colloidal particles on the hydrogel core. The properties of
the shell can be varied to control the rate of release of
encapsulated drugs [60,61].
21) Thin film drug delivery vehicles are made up of
hydrophilic polymers. They rapidly dissolve on the
tongue or buccal cavity and delivers the drug(s) to the
systemic circulation via dissolution when contact with
liquid is made. Thin film drug delivery vehicles have
emerged as an advanced alternative to the traditional
tablets, capsules and liquids. Similar in size, shape and
thickness to a postage stamp, thin film strips are typically
designed for oral administration, with the user placing
the strip on or under the tongue (sublingual) or along the
inside of the cheek (buccal). These drug delivery options
allow the medication to bypass the first pass metabolism
thereby making the medication more bioavailable .
As the strip dissolves, the drug can enter the blood
stream enterically, buccally or sublingually.
22) Fast dissolving tablet is designed for oral admini-
stration of solid dosage form of medicine in absence of
fluid or water. Such tablets, when put on tongue dissolve
in saliva instantaneously (within 60 sec) and release
drug(s). They are found to be suitable during traveling
where water may not be available [63,64].
Recently, tablets with dual-delivery capabilities using
“bi-layered dual-release technology” have been devel-
oped. Such tablets incorporate both an immediate-release
and one or two controlled-release components having
unique release profiles at different rates for one or more
23) Implantable drug delivery vehicles developed till
date includes 1) Ceramic implants and 2) Silastic im-
plants. Ceramic implants are made up of bioceramics.
Among bioceramics, silica-based ordered mesoporous
materials are unique candidates as bone implants due to
two reasons: a) bioactive nature of such materials in
contact with simulated body fluids, i.e., a carbonate hy-
droxyapatite similar to the mineral phase of bone is
formed onto the material surfaces; b) their ability to act
as delivery systems of many drugs to treat bone inflam-
mation, infection, diseases and promote bone tissue re-
generation using proteins, peptides, growth factors, and
other osteogenic agents [66-69]. Therefore, in recent
years, ceramic implants have gained attention as drug
delivery carriers/ systems for bone regeneration therapies.
On the other hand, silastic implants are made up of a
silicon rubber membrane. These implants filled with
drug(s) have been designed to provide a convenient and
reliable method for the delivery of physiological concen-
trations of drug(s) viz., progesterone, nestorone [70,71].
These vehicles offer various advantages such as mainte-
nance of therapeutic blood levels, improved patient com-
pliance, and improved safety.
24) Controlled release formulations can be catego-
rized into 3 subgroups: a) rate controlled release, b) de-
layed release, and c) pulse release formulations. Pulse
release formulations are dealt with a branch of medicine
called “chronotherapeutics”. It deals with effects of bio-
logical clocks or circadian rhythms in human health .
It is a method of treatment where in vivo availability of
drug is timed to match rhythms of disease. Therefore,
this method optimizes therapeutic effects/ out comes of
drug(s) and minimizes its side effects.
25) Drug loaded erythrocytes is one of the potential
systems for targeted delivery of drugs, particularly to the
reticulo-endothelial system. Erythrocytes are biocom-
patible, biodegradable, and possess long circulation half-
life. They can be loaded with variety of biologically ac-
tive substances. Through Erythrocyte Engineering, “car-
rier erythrocytes” are prepared by collecting blood sam-
ple from the organism of interest and separating RBCs
from plasma. By using various physico-chemical meth-
ods, RBCs are systematically ruptured and the drug is
entrapped into the erythrocytes, finally they are resealed
and the resultant carriers are then called “resealed eryth-
rocytes”. Upon reinjection, the drug loaded erythrocytes
serve as slow circulation depots, and prevents degrada-
tion of loaded drug(s) from inactivation by endogenous
enzymes and chemicals. They provide steady state con-
centration of drug(s) and decrease the side-effects of
loaded drug(s). Nowadays, through Erythrocyte Engi-
neering, Nanoerythrosomes based drug delivery systems
are being developed [72,73].
26) Self-emulsifying drug delivery systems (SEDDS)
is an isotropic mixture of oils, surfactants and sometimes
co-solvents. Self-emulsifying sustained/controlled-release
pellets, capsules, suppositories and nanoparticles are be-
ing extensively investigated as drug delivery carriers.
These multi-component delivery systems have been op-
timized by evaluating their ability to self-emulsify when
introduced to an aqueous medium under gentle agitation,
and by determination of particle size of the resulting
emulsion. Upon oral administration, these systems form
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug Delivery Systems
micro-emulsions in the gastrointestinal tract . As
drug delivery vehicles, SEDDS are best suited for the
delivery of hydrophobic or lipophilic drugs. This self-
emulsifying formulation greatly enhances the bioavail-
ability and site-specific targeting of highly lipophilic
27) Research in micro-endoscopy is devoted to minia-
turization of drug delivery devices/systems for intra-
corporeal use. In this approach, endoscopic function is
increased by integrating its tip with Microsystems. The
main aim of this research on diagnostic and therapeutic
procedures is to reduce pain and discomfort and improve
the quality of patient care. Recently, two groups of in-
vestigators have reported the development of endoscopic
pills or endoscopic wireless devices .
28) Topical systems include phonophoresis and ionto-
phoresis. Phonophoresis (a combination of ultrasound
therapy and topical drug therapy) is a method of trans-
porting drug(s) through skin using ultrasound (a sound
wave outside the normal human hearing range). Now it is
being used by physiotherapists to achieve therapeutic
drug(s) concentrations at specific sites below skin .
Iontophoresis is an electro-chemical method of inducing
migration of ionic drugs into skin by electrostatic repul-
sion at active electrode (by creating a potential gradient).
Positively charged drugs are delivered by anode, whereas
negatively charged ones by cathode. Its merits and limi-
tations are well explained by Manabe and colleagues
3. Drug Delivery Routes
The routes of administration of a drug(s) are mainly de-
pendant on the properties of the drug(s) (for example,
solubility, susceptibility to degradation by enzymes etc),
access to a disease location, effectiveness in dealing with
the specific disease and patient acceptability. The most
preferred drug delivery route is the oral route. It is well
known that most of the drugs which offer the greatest
potential for more effective therapeutics are protein- and
peptide-based. Therefore, they do not easily cross muco-
sal surfaces and biological membranes; they are easily
denatured or degraded; prone to rapid metabolic clear-
ance in the liver and other tissues of the body; and re-
quire precise dosing. At present, peptide, protein, anti-
body, vaccine and gene based drugs are generally ad-
ministered by injection or a nanoneedle array . This
route is, however, less pleasant and also poses problems
of oscillating blood-drug concentrations. Thus, despite
the barriers to successful drug delivery that exists in the
gastrointestinal tract, the oral route of drug administra-
tion is still the most preferred one; as it offers advantages
of convenience and cheapness of administration. At pre-
sent, drug(s) are also administered through other routes,
such as topical (skin), transmucosal (buccal, sublingual,
ocular, nasal, vaginal and rectal) and inhalation routes
1) Oral route of mucoadhesive drug delivery systems
provides advantages of high accessibility and low enzy-
matic activity. Earlier the hydrophilic polymers (like
SCMC, HPC and polycarbophil) were used for the treat-
ment of periodontal diseases, but now attempts are being
made to the effective utilization of these systems to the
delivery of peptides, proteins and polysaccharides .
2) Parenteral routes include all routes which are
other than oral. They are very promising and include
subcutaneous, intravenous, intramuscular routes etc.
Among nanomaterials, only liposomes have been admin-
istered intravenously. Nanoscale drug vehicles have been
found to have great potential for improving the delivery
of drugs through sublingual and nasal routes, as both of
them avoid first-pass metabolism and for difficult-access
brain, intra-articular and ocular cavities . The active
drug macromolecules are capable of associating with
nanoparticles, thus making the systemic delivery of pep-
tides and vaccines feasible through the nasal route.
Moreover, there is a feasibility of improving the occular
bioavailability of drugs if administered through a colloi-
dal drug carrier . Buccal and (or) sublingual routes of
drug delivery uses a “dissolving film” or “oral drug strip”
to administer drug(s) via absorption in the mouth and/or
via the small intestines (enterically). Evaluating the sys-
temic transmucosal drug delivery, the buccal mucosa is
the preferred region as compared to the sublingual mu-
3) Trans-tissue and local delivery systems are needed
to be firmly fixed to resected tissues during surgery with
an aim to produce an enhanced pharmacological effect,
while minimizing systemic, administration-associated
toxicity. Trans-tissue systems include: drug-loaded ge-
latinous gels, which are formed in-situ and adhere to re-
sected tissues, releasing drugs, proteins or gene-encoding
adenoviruses; antibody-fixed gelatinous gels (cytokine
barrier) that form a barrier, which, on a target tissue
could prevent the permeation of cytokines into that tissue;
cell-based delivery, which involves a gene-transduced
oral mucosal epithelial cell (OMEC)-implanted sheet;
device-directed delivery—a rechargeable drug infusion
device that can be attached to the resected site.
4) Transdermal delivery of drug(s) is accompanied
by formulations like transdermal patches, gels and sprays.
A transdermal patch is placed on the skin to deliver a
sustained release dose of medication through the skin.
This system provides controlled release of the drug in the
patient, and enables a steady blood-level profile, leading
to reduced systemic side effects and, sometimes, im-
proved efficacy over other dosage forms. A less elegant
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug Delivery Systems551
but effective alternative to a transdermal patch system is
a conventional topical vehicle such as a gel. Such a for-
mulation shows a clinically equivalent performance to
that of a patch with lesser skin irritation and good com-
pliance. Recently developed “Metered dose transdermal
spray” (MDTS) is better alternative to both the patch and
gel systems, as the sprays form the film that is quick
drying, easy to use, well tolerated and non-occlusive. The
MDTS formulations are topical aerosols formulated as
single phase solutions consisting of drug, polymers and
penetration enhancers [Axiron (testosterone transdermal
metered-dose transdermal system) by Acrux/Eli Lilly]
[81,82]. New metered dose transdermal sprays have
broadened the patient acceptance and compliance. These
methods can be used for symptoms of menopause, fe-
male androgen insufficiency, severe pain, central nervous
system disorders, male androgen insufficiency, urinary
incontinence, contraception and smoking cessation.
Transdermal drug delivery systems have potential for
systemic delivery of drugs with low oral bioavailability
and high first pass effect. Transdermal delivery systems
skip the problems of interference due to presence of food
in the stomach, gastrointestinal modification (viz., hy-
drolytic, enzymatic, bacterial fermentation), metabolism,
and variation in delivery rates. This technique is aes-
thetically accepted and usually non-invasive; and can be
used to provide topical (local) delivery over weeks/
months. It is suitable for unconscious patients but suffers
from lack of dose flexibility, slow penetration rates and
restricted to low dosage drugs .
5) Pulmonary delivery of drug(s) is accomplished by
aerosols, nebulizers (solutions), powders (dry powder
inhaler, DPIs), and metered-dose inhalers (MDIs). All of
these utilize nanostructures like dendrimers, micelles,
nanoparticles etc. Pulmonary drug delivery systems have
been successfully used for local targeting for the treat-
ment of respiratory diseases, as well it has the potential
for effective delivery of numerous drugs systemically, as
explicitely explained by Shaikh and coworkers .
6) For gene delivery, the plasmid DNA must be intro-
duced into the host cells, followed by its transcription
and translation into the corresponding protein. To
achieve this goal, few hurdles must be overcome by the
gene delivery system as the transfection is affected by: 1)
targeting the delivery system to the host cell, 2) transport
through the cell membrane, 3) uptake and degradation in
the endolysosomes, and 4) intracellular trafficking of
plasmid DNA to the nucleus. Therefore, the delivery of
genes for treating genetic diseases still remains a chal-
7) Acoustic targeted drug delivery (ATDD) is a
method that uses ultrasound energy to enhance the
transport of molecules into and (or) across specific tis-
sues . Generally, this class of ultrasound energy falls
under the class of therapeutic ultrasound, and ranges in
ultrasonic frequencies of 1 - 20 MHz. The use of ATDD
in conjunction with local drug delivery by injection,
topical application and convection-enhanced delivery
shows promise to significantly enhance the treatment of
various diseases in the human body by specifically tar-
geting the drug(s) into the tissue .
4. Applications of Drug Delivery Technology
Significant changes in the healthcare industry have led
pharmaceutical companies to depend mainly on ad-
vanced drug delivery technology to produce distinctive
drugs and remain competitive. In addition, soaring R&D
costs, long timeframes for developing drugs from new
chemical entities, and increasing consumer demand for
better, more convenient medicines, pharmaceutical com-
panies are using creative strategies that capitalize on the
capabilities of drug delivery technology. Therefore, a
growing number of pharmaceutical companies are now
applying the technologies of drug-delivery companies to
enhance the convenience, safety, and efficacy of cur-
rently marketed drugs and drug products. Drug delivery
companies, in turn, are developing more sophisticated
technologies to meet new demands of patients and the
pharmaceutical industry. Against this background, inno-
vative pharmaceutical companies are partnering with
drug delivery companies to find new ways of developing
advanced medications to meet these market demands.
Therefore, they are employing lower-risk strategies to
develop existing medicines into improved therapies rap-
idly, with lower development costs and attrition rates.
For example, a UK-based pharmaceutical company
named “Arakis Limited” formed a strategic partnership
with US-based Penwest (an oral drug delivery and de-
velopment company) to develop ‘Performance-Enhanced
Medicines’ (PEMs). PEMs are drugs that have been sub-
stantially improved, clinically and commercially, by drug
delivery technology. The strategy for producing PEMs is
creatively simple. Arakis takes advantage of new discov-
eries in medical science and genomics to identify and
acquire existing drugs that can be improved through drug
delivery to satisfy the unmet medical needs of specific
disease populations. Patient genotyping and metabolic
profiling are valuable tools for selecting specific patient
populations in which a drug will be particularly effective.
Thus, successful development of PEMs improve the
drug’s therapeutic benefit, efficacy, safety, delivery pro-
file or dosage, and reduce side effects.
The applications of fine particle approach based drug
delivery technology to the pharmaceutical industries
have the potential to:
1) extend patent life of existing drugs through re-for-
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug Delivery Systems
mulation based upon fine-particle platform;
2) improve the likelihood of development success for
new compounds and novel agents which face a) water
solubility problems, b) protein and peptide drugs delivery
problems by stabilizing them through Supercritical Fluid
(SCF) Technology [86-90];
3) improve effectiveness of a drug and/or device
4) help solve drug delivery problems.
Thus, application of drug delivery technology to
pharma companies provides immense opportunity to en-
hance value for currently marketed drugs, drug-related
5. Market Scenario of Drug Delivery
Recent report of the major types of drug delivery systems
used in the healthcare industry and comprehensive cov-
erage of the pharmaceuticals markets has documented
that the global market for advanced drug delivery sys-
tems amounted to $139 billion in 2009. The estimate for
2014 is $196.4 billion, for a compound annual growth
rate (CAGR) of 7.2% in the 5-year period. The largest
segment of the market is targeted drug delivery ($50.9
billion in 2009) which is expected to increase to $80.2
billion in 2014, for a CAGR of 9.5%. Sustained-release
products have the second largest market share ($ 36.1
billion in 2009) and are expected to rise to $ 45.8 billion
in 2014, for a CAGR of 4.9% .
6. Conclusions with Future Opportunities
In nutshell, majority of recent advances in drug delivery
systems are primarily based on the nanotechnology.
Nanomaterials and nanoformulations provide immense
benefits to the drug delivery, targeting, release and have
additional potential to combine diagnosis and therapy.
Therefore, they are emerging successfully as one of the
major tools in nanomedicine.
Nanomaterials based drug delivery systems have
greater potential for many applications, like AIDS ther-
apy, anti-tumor therapy, gene therapy, radiotherapy, in
the delivery of antibiotics, proteins, vaccines, virostatics,
and as vesicles to pass the blood-brain barrier. The main
goals are to improve their stability in the biological en-
vironment, to mediate the bio-distribution of active com-
pounds, improve drug loading, targeting, transport, re-
lease, and interaction with biological barriers. In certain
cases, cytotoxicity of nanomaterials or their degradation
products remains a major problem. Thus, improvements
in biocompatibility of such materials are major concern
of future research. Moreover, there are several techno-
logical challenges to be overcome, in developing nano-
materials based drug delivery systems:
1) Those delivering highly localized, large quantities
of drug(s) to specific sites must release drug(s) in con-
2) Controllable release profiles must be obtained for
3) Nanomaterials must be made up of biocompatible
and biodegradable substances;
4) Structures should be like biomimetic polymers and
5) Should function as active drug targeting/on-com-
mand delivery/systems interacting with the body/targeted
or smart drug delivery/ intelligent drug release devices or
bioresponsive triggered systems/self-regulated delivery
6) Must be virus-like systems for intracellular deliv-
7) Must have nanoparticles to improve devices such as
implantable devices/nanochips for nanoparticle release,
or multi-reservoir drug delivery-chips;
8) Nanoparticles must be made for tissue engineering;
e.g. for the delivery of cytokines to control cellular
growth and differentiation, and stimulate regeneration; or
for coating implants with nanoparticles in biodegradable
polymer layers for sustained release;
9) Advanced polymeric carriers for the delivery of
therapeutic peptide or proteins or biopharmaceutics;
10) In the development of Combined therapy and
medical imaging, for e.g., nanoparticles for diagnosis and
manipulation during surgery (e.g. thermotherapy with
11) Universal formulation schemes that can be used as
intravenous, intramuscular or oral drugs;
12) Cell and gene targeting systems;
13) Must be user-friendly lab-on-a-chip devices for
point-of-care and disease prevention and control at home;
14) Devices for detecting changes in magnetic or
physical properties after specific binding of ligands on
paramagnetic nanoparticles that can correlate with the
amount of ligand;
15) Must serve as better disease markers in terms of
sensitivity and specificity;
16) Insolubility issues of the past have provoked a
paradigm change, which now offered a novel solution
called SEDDS which needs further exploration and re-
search so as to bring out commercially available self-
Apart from these, developing oral drug delivery vehi-
cles for e.g. “oral strips” need plasticizers in its formula-
tions. However, plasticizers are not free from health haz-
ards, as 90% of the plasticizers belong to a family of in-
dustrial compounds called “Phthalates”. All of the phtha-
lates are ubiquitous environmental contaminants or per-
Copyright © 2011 SciRes. JBNB
Bird’s Eye View on the Recent Advances in Drug Delivery Systems553
sistent organic pollutants (POP) or POP-like compounds,
as well linked to a range of adverse reproductive effects
[92-95]. Therefore, utmost care must be taken about any
adverse health impact associated with the organic or in-
organic elements and compounds used in developing any
drug delivery systems.
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