Vol.2, No.1, 41-48 (2010) Natural Science
Copyright © 2010 SciRes. OPEN ACCESS
Review on nano-drugs
Yong Liu1,3, Tian-Shui Niu2, Long Zhang1, Jian-She Yang1,2
1Key Laboratory for Natural Medicine, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, China
2China Life Science College of Northwest Normal University, Lanzhou, China
3Graduate School of Chinese Academy of Sciences, Beijing, China
Received 25 September 2009; revised 20 October 2009; accepted 22 October 2009.
Nano materials is a new type of drug carriers
with very promising application. In recent years,
great progress was achieved in making drugs
own the characteristics of targeted and con-
trolled release via nanotechnologies. This paper
addressed the capability of nano drugs on tar-
geting to cells, penetrating through epicyte,
controlled release and the security issues re-
sulting from its using. We gave the prospect of
nano drugs in biology and medicine applying.
Keywords: Nano Drug; Targeting; Cell Penetration;
Controlled Release
Nano drug is an important product of the rapidly devel-
oping nanotechnologies in biology and medicine field
[1]. Drug is wraped in or adsorbed on surface of
nanoparticles, when the specific targeting molecules
combining with the receptor of cell surface, nano-drug is
taken into cells, to achieve the safe and effective targeted
drug delivery and gene therapy. Because Nano-drug car-
riers have high targeting, favorable sustained, controlled
release capability and superior cell penetration ability, it
can improve efficacy of drugs and reduce side effects. It
is the production of nano-technology combining with
modern medicine [2-3].
There are three main types of drug-loaded nanoparti-
cles at the present time. First, the common drug-loaded
particles: according to pharmacy technology bind with
nanotechnology, with special methods to make the drug
that physical-chemical property are unsteady and easy to
be degradated or has considerable bad reaction to impact
on the use highly dispersed in the drug carrier. Second,
the controlled-release drug-loaded particles: be different
from routine drug-loaded particles, this kind of drug’s
release process of nano-particles have a specific law. The
dissolution of sac wall and the role of micro-organisms
could make the drug in the heart of sac spread out.
According to different purposes, choose a suitable tim-
ber and technology to make particles gather on the local
tissue and attaine effective concentration, without caus-
ing general toxicity reaction. Third, the targeting drug-
loaded particles: according to the needs of clinical,
choose different carriers that have different affinity to
different organizations or diseased region to make dif-
ferent carrier particles, or combine monoclonal antibody
with the carrier, or under the effect of external magnetic
field so that the drug can be transported to the particular
site that we expected. Because nano-technology has
changed the physical space of the drug, physical-
chemical and biological property of drugs has surprising
change. The changes mainly include the following as-
pects [2-7]: 1) Nanoscale drug carriers can enter into the
capillaries, and freely flow in the blood circulation. It
also can go through cells, be absorbed though pinocyto-
sis by histiocyte and enhance bio-availability of drug; 2)
Because the specific surface area of nano-drug carriers is
very high, solubility of poor water-soluble drugs in the
nano-carrier is relative enhanced and overcome the
problems preparation with conventional methods; 3)
Nano-carriers can be made to targeted position system,
decrease the dose of drug and reduce the side effects
with special processing. 4) By controlling the degradable
speed of polymers in vivo, Nano-carriers can extend
biological half-life of drug, improve the efficacy of the
short-half-life drugs and reduce side effects of medication.
5) Because of Eliminateing the limit of specifial barriers
such as blood-brain barrier, blood-ocular barrier and cell
membrane barrier to the drug, nano-particulate drug carri-
ers can pass through these barriers to treat scathing sites.
The central principle of nano-drug carrier is to realize
drugs delivery “effective, safe and controllable”. There-
fore, targeting, controlled release and safety of drugs is
an important and topical issues in pharmacy researchful
area. The emergence of nano-delivery system make fea-
sible to realize targeting and controlling release of drug.
This paper expounds nano-drug delivery research in the
field of medicine around the core.
Nano-drugs can selective distribute the object, to en-
42 Y. Liu et al. / Natural Science 2 (2010) 41-48
Copyright © 2010 SciRes. OPEN ACCESS
hance efficacy and reduce side effects. The role of the
object from the target organ, target cell to the most ad-
vanced structure in the target cells. The three levels
method of targeted therapy all could complete with
nanotechnology. Nano-targeting drugs can be divided
into passive targeting and active targeting.
2.1. Passive Targeting
Studies found that small particle size passive targeting
drugs can spontaneously gather the diseased region
making use of EPR (Enhanced Permeability and Reten-
tion) to achieve the purpose of passive targeting [8]. Be-
cause the blood capillary's permeability of the damage
spot which caused by tumor, inflammation, hypertension
and so on is higher than that of the normal blood vessel,
simultaneous discharge capacity of lymph blood vessel
is weaken. So in vivo long circulation the biological
compatible macro-molecule, the medicine carrier, the
molecular assembly are easier through blood vessel that
injuries portion into the organization and assemble. The
EPR is special useful to treat the tumor and blocks [9].
One of the ways to enhance EPR is strengthening the
stability of drug to lengthen circulation time of drug in
vivo. So the drug carriers have more opportunities to go
through the target position and get together [10]. The
passive targeting preparation include of micro-capsule,
microsphere, nanopartieleliposome and so on. The
liquid crystal, fluid film, lipin, lipoid, protein and bio-
degradation high polymer material is often used as car-
rier material.
Mitra [11] studied the tumor targeting using dex-
tran-doxorubicin-chitosan nanoparticles and showed that
nanoparticles was not only reducing peripheral side ef-
fects, but also greatly improving the treatment of solid
tumors. Du, et al. [12] made the carrier complex system
with cyclic arginine-glycine-aspartic acid and lipid and
combined interferon-α1b to treat liver fibrosis in rats,
showed that according to combine with carrier the
concentration of interferon-α1b in the liver of rats was
up to 10 times and the degree of liver fibrosis was sig-
nificantly reduced comparing with non-carrier group.
This illustrated the complex vector had a clear targeting
to the liver. Briz [13-15] made two kinds of chelate
compound with bile acid glycine-cisplatin and ursode-
oxycholic acid-cisplatin, through the result of in vivo
experiments showed that two complexes had a good
affinity to the tumor cells of liver, and the absorbed dose
was obvious higher than the original drug. Because of
lower toxicity, these chelate compounds can extend more
survival time of mice tumor transplant than the original
drug. They also had effect to the chemical sproof tumor
cells, and partly decrease physiological tolerance of tu-
mor to the cisplatin.
2.2. Active Targeting
Active targeting is that drug carriers through the surface
of nano-ligand binding specificity of targeting delivers
drugs to specific organizations or release drugs in vivo
under the certain physical conditions. The conventional
active targeting mechanisms include three kinds. First,
thermal-sensitive and pH-sensitive targeting, that is, suf-
ficiently use the changes of temperature and acidity that
different body tissues and organs in the pathological
process. Choose the polymer containing thermo-sensi-
tive or pH-sensitive (such as N-isopropylacrylamide, etc.)
component to form the polymer micelle. Drug-loaded
micelles in the specific temperature or acidity can be
easily depolymerized and released the drugs [16-18].
Thomas [19] reported a new type of temperature-sen-
sitive nanoparticles. The critical solution temperature is
30. The drug was wraped in the nanoparticles and the
slow releaseing could last one month in vitro. When the
temperature was more than 37, the nanoparticles could
priority be uptaken by the MDA2MB2231 breast cancer
cells. This temperature-sensitive nanoparticles has great
potential in the the treatment of thermal sensitivity tar-
geting to the solid tumors.
Na [20] made PA-SDM nanoparticle with the amy-
lopectin acetate (PA) and sulfanilamidesulfamidyl (SDM)
that loadding adriamycin (ADR). The nanoparticles
could change the rate of ADR release along with the
alkalinity acidity change. As the pH value of the tumor
spot was different from that of normal tissue, PA-SDM
nanoparticles could selectively accumulate on the breast
cancer cells MCF-7 and speed up the release, enhanced
cytotoxicity to the tumour.
Yoo [21] got the pH-sensitive polymer micelles com-
plex by linking ADR with acid-sensitive. Taking advan-
tage of meta-acid physiological characteristic of the tu-
mor organization partial micro environment, adriamycin
hydrolysis from the polymer micelles down when the
drugs reached to the tumor site. Thereby enhanced the
concentration of ADR in the tumor cells and increased
efficacy of the drug.
These belong to the studies of the targeted drug deliv-
ery that in response to the environment, when the drug
carriers meet with environmental stimulative, they are
depolymerized to the monomers and drugs releases out
of the vector. When combine EPR effect, nano-drug car-
riers that environment respond can further enhance the
efficacy of antineoplastic.
Secondly, drug carriers can be modifed by combining
with special targeting ligand (antibodies, lectins, sugars,
hormones, etc.). Thereafter, this carrier-ligand complex-
ity can be specifically identified by the epicyte receptors
and accurately transmitted to the target spot.
Xiao [22] made the starch nanoparticles (StNP)
charged negative electricity with reverse microemulsion
and cross-linking methods, after StNP was modificed by
a folic acid active substances (FA-PEG-NH2) modific-
tion, they successfully prepared the folic acid-starch
Y. Liu et al. / Natural Science 2 (2010) 41-48 43
Copyright © 2010 SciRes. OPEN ACCESS
nanoparticles (FA-PEG/StNP) which the average diame-
ter was about 130 nm. FA-PEG/StNP was combined
with the anti-cancer drug doxorubicin (DOX) through
penetration and got nano-drug containing folic acid-
starch. Compared with StNP through hepatoma cells
(BEL7404) culture experiments found that the cell le-
thality of using FA-PEG/StNP carrier was 3 times higher
than that of StNP carrier. The result proved that FA was
modified on the particles can significantly increased the
particle targetting to the liver targeting cancer cells,
made more drugs actting on the tumor cells and en-
hanced the drug’s effect.
Jie [23] synthesized nanoparticles (NPs) of the blend
of a component copolymer for targeted chemotherapy
with paclitaxel used as model drug. The component was
poly (lactide)-D-a-tocopheryl polyethylene glycol suc-
cinate (PLA-TPGS), which was of desired hydropho-
bic-lipophilic balance, which facilitates the folate con-
jugation for targeting. The nanoparticles were decorated
by folate. The drugs were evidently promoted to target-
ing gather the surface of the breast cancer cells (MCF-7)
and C6 glioma cells, thereby enhancing its efficacy.
Terada [24] established the specific targetting drug
delivery system to the human hepatoma cell line (HCC).
Through amino of dioleoyl phosphatidylethanolamine
(DOPE) linked to substrate peptide of peginterferon ma-
trix metalloproteinase-2 that was modified by PEG and
obtained PEG-PD, which could be enzymed cut by ma-
trix metalloproteinase-2, then integrated the PEG-PD
into the galactose-liposome and got the GaL-PEG-PD-
liposomes. Because the steric effect caused by PEG
shielding the galactosyl of the surface of liposome com-
plex, GaL-PEG-PD-liposomes could not be uptaken by
the normal liver cells. But there was has high concentra-
tion of secreted matrix metalloproteinase-2 around the
HCC cells and could hydrolysis the peptide of Gal-
PEG-PD-liposomes to remove the polyethylene glycol,
relief the steric effects of polyethylene glycol, exposure
the galactose residues of liposome surface. At this time
the liposome could be recognised and uptaken by HCC
cells and got the purpose of specific targeting to HCC
Thirdly, suitable adjuvant was encapsulated into the
micelles with physical method. The micellar will pulse
release drug under the influence of the external excita-
tion conditions (such as IR light, magnetic field). The
adjuvant does not affect performance of micelles (stabil-
ity, permeability, etc.), but impact the performance of the
drug that is wrapped up in micellars (under certain con-
ditions, hydrophilic can be converted to lipophilic, etc.).
For example, Sershen [25] prepared N-isopropylacry-
lamide hydrogel could encapsulate γ-Fe2O3. Under the
effect of outside magnetic field, when the temperature of
hydrogel rised 10 and is higher than the critical so-
lution temperature, hydrogel will rupture and sudden
release the drugs.
Nanoparticles interacte with electromagnetic pulse or
ultrasonic pulse can also enhance the release of drug.
When the nanoparticles reach to the tumor vascular sys-
tem and was adsorbed to the vessel wall, because elec-
tromagnetic pulse or ultrasonic pulse lead to the local
thermal effects and further caused cavitation, tumor cell
membrane is perforated, large molecular drugs enter into
the cancer cells from blood, play the therapeutic effect.
There are many natural biological barriers to prevent the
body suffering damage, such as blood brain barrier,
blood-eye barrier, biomembrane barrier and so on, but
the existence of these barriers also gives the difficulty to
the treatment of morbidity spot. Nanoparticles is solid
colloid particles that composed of macromolecule sub-
stance and the particlesize is 1~1000nm. It can pass
various barriers. But as drug-carrier, if it can use its cell
penetration and carries bioactive molecules into the tar-
geting cell is the key problem of drug playing curative
effect. In order to solve this problem, the researchers
tested many sorts of nanomaterials. Yue [26] prepared
nanometer sized-liposome that was produced from
phosphatidylcholine to encapsulate fluorescent dyes 10-6
fluorescein isothiocyanate ihydrochloride (FITC), 10-6
Rhodamine B (RhoB). Liposome and fluorescent dyes
was put into culture medium. After 2h, the result of con-
focal microscope screen showed that the FITC and Rho
B couldn’t go through cell membranes, fluorescence
didn’t exist in the cell, but green and red fluorescence
were obserived in the liposomes groups. This explained
that nano-liposomes could go into cell by cell endocyto-
sis or fusion process, transfer fluorescent reagent that
couldn’t through membrane into cells. When the
FITC-liposomes and liposomes Rho B coacted on cell,
yellow fluorescence exited in cell, this account for lipo-
somes containing different substances could into the cell
at the same time.
According to Sivararnakrishnan [27] report, Be-
tamethasone 17-valerat (BMV)-SIM had a good stability
compared to traditional drug emulsion and skin absorp-
tion increased. In recycling experiments, the drug dose
of skin containing was above 75%.
Ding [28] prepared monostearin solid lipid nanoparti-
cles (MSIN), investigated the cellular uptake of MSIN
and the influence on the cellular uptake by MSIN modi-
fied with PEG2000 in human-type cell alveolar epi-
thelial cell line (A549) and murine macrophages cell line
(J774A1). Rhodamine was incorporated into solid lipid
nanopartides as fluorescent marker. The experimental
results showed MSIN that was modified with PEG2000
had low toxicity to cell and had good physiological
compatibility. It was also highly taken by A549 cell line
44 Y. Liu et al. / Natural Science 2 (2010) 41-48
Copyright © 2010 SciRes. OPEN ACCESS
and could be fast reached to saturation. Pantarotto [29]
prepared single walled carbon nanotubes modified by
derivatization and single walled carbon nanotubes cou-
pling peptides. They were all marked by FITC. Investi-
gated the cellular uptake of the two-type functionalized
carbon nanotubes (f2CNTs) and found that they all could
penetrate the cell membrane: CNT1 mainly entered into
the cytoplasm and the CNT2 that was modified by pep-
tide could enter into the nucleus.
The studies also found that nano-materials that were
uptaken by cells have the size critical point. Becker [30]
prepared DNA-wrapped single-walled cabon and inves-
tigated length-dependent cellular uptaken of these car-
bon nanotubes. Studies showed that the cellular uptake
of carbon nanotubes had a choice of lengths and the
cut-off point was (180±17) nm. They speculated that
different cell might have different selective range of
length to uptake the carbon nanotubes. Ito [31] used
carbon nanotubes as EPO (erythropoietin, EPO) oral
agent vector and found that the short carbon nanotubes
could be used to carry more EPO to the target cells ap-
proved the speculation of Becker.
Nano-drug interactions with nano-carrier and made to be
the controlled-release formulations with appropriate
methods. When drug-carrier complex enter into the body,
the drug is slowly released out of nanoparticles at the
constant speed automatic in the scheduled time through
the leaching, infiltration and proliferation or dissolution
and act on the specific organ, tissue and cell. In addition,
the nano-carriers prevent drug be degraded by various
enzyme, extends the effective time of drugs. At the same
time this controlled-release nano-drug can reduce the
peak phenomenon of blood concentration, reduce side
effects and improve efficacy. Mainly through diffusion
control, chemical control, solvent control and other
methods to achieve the purpose of controlled release of
drug. Generally speaking, a controlled-release prepara-
tion has two or more controlled-release mechanisms.
4.1. Diffusion-Controlled Release
Drugs or other biologically active substances are com-
bined with carriers; the drug is released in a certain of
time and at a certain rate to the environment through
diffusion. Diffusion-controlled is the most common
mechanism in the controlled-release of drug delivery
system, especially the nondegradable polymers carriers;
the drug is mainly through this way released. In a biode-
gradable polymer carriers, when material degradation
rate is slower than the diffusion of drug, diffusion of the
drug still play a leading role in the release. There are
many factors impact the diffusion-controlled release,
such as geometric designs of system, condition and qual-
ity of ambient medium, the character and structure of the
host materials, the solubility and loading amount of the
drug [32].
4.2. Chemical-Controlled Release
Through hydrolysis, zymohydrolysis and other chemical
reactions, chemical-controlled release system control the
rate of drug release. According to the role of drug and
substrate, mechanism of release, Chemical controlled
system can be divided into degradable system and
side-chain system. 1) Degradable system: the biological
activity drugs is embedded or dispersed in biodegradable
polymer, but there is no chemical bonding effects be-
tween drug and polymer, the rate of drug release is con-
trolled by the rate of polymer degradation and erosion.
The material of drug carrier is mainly include of biode-
gradable poly vinegar (such as polylactic acid, poly-
caprolactone with vinegar), poly polysaccharide (such as
chitosan, gelatin), and so on. These materials is non-
toxic, and the ultimate metabolites can be discharged in
vitro or absorbed by organism, through regulating the
rate of polymer degradation or dissolution to controll the
release of drug on a specific location within regular hour.
In these systems, the rate of polymer degradation or dis-
solution mainly influence the rate of drug’s release, but
the speed of degradation or dissolution also has an im-
portant relationship with the quality of the polymer (such
as polymer molecular weight, crystallinity, the hydro-
philic property and hydrophobicity, etc.), many re-
searchers controlled and regulated the rate of degrada-
tion or dissolution material with chemical or physical
methods such as reshaping, modification, blending to the
polymer, further regulate the speed of drug release. But
the nature of drug is also an important factor of the
drug’s release [33]. 2) The side-chain system of drug
carrier may be degradable type or nondegradable type.
Through the chemical bond that can be hydrolyzed or
enzymolied, drugs in the side-chain system can be con-
nected to the primary chain or side chain (side chain can
be used to change the drug’s release rate) of polymer.
The release of drug is controllied through hydrolysis or
Qing [34] used bovine serum albumin (BSA) as the
model drug, at first, the nanoparticles containing pro-
teins were obtained by absorbing BSA from the solution
onto the surface of nano-scale SiO2, then, PLGA micro-
sphere loading the solid nanoparticles were fabricated
with the solid-in-oil-in-water-emulsion method. Study
found with the increasing of the mass fraction of BSA in
the product of adsorption, the rate of solvent controlled
release of BSA is faster. The main mechanism of drug
release is the diffusion of drugs and the degradation of
the polymer. In the release process, the BSA that was on
the surface of microspheres was first diffused and
Y. Liu et al. / Natural Science 2 (2010) 41-48 45
Copyright © 2010 SciRes. OPEN ACCESS
formed pores. It was conducive to the diffusion of the
BSA in the inner layer. Water also could go into the mi-
crospheres and resulted in the degradation of micro-
spheres. Microspheres that loaded more drugs diffused
more BSA in the early period and also the pores that
formed were more and larger, the degradation of the mi-
crospheres is faster in the late period, so release of BSA
was faster.
Yang [35] prepared microspheres that containing an-
tiphthisic drug Rifampin was prepared from poly lac-
tic-co-glycolic acid (PLGA) as carrier by emulsion and
solvent evaporation method. In vitro experiment of re-
lease, investigated the performance of PLGA micro-
spheres that was as a carrier of drug delivery. The release
time of rifampicin in the PLGA microspheres was more
than 30 days, and there was no obvious phenomenon of
sudden release. But the release of the mass fraction of
rifampicin without microspheroidization was up to 96%
in 10 minutes. At the same time, they found PLGA mo-
lecular weight and the LLA / GA mass ratio had signifi-
cant impact on the time of the release [36,37]. Because
the rate of degradation of low molecular weight PLGA
was significantly higher than that of high molecular
weight and in the PLGA copolymer, with the GA mass
increaseing, hydrophilicity of PLGA enhanced, the deg-
radation significantly speed up. While the rate of the
drug’s release was mainly controlled by the degradable
rate, so with the reducing of PLGA molecular weight
and LLA/GA mass ratio, the release of rifampicin speed
up. The drug release was simultaneously controlled by
drug-diffusion and degradation of carrier material, but in
this system, degradation played a decisive role in the
mechanism of control. Observed the surface morphology
of the degradation rifampicin-PLGA microspheres, they
found the surface and inside of microspheres appeared
large holes, spherical shape almost disappeared, the red
faded and turned to white. These result showed that in
early period the drug’s release was out of carrier materi-
als only through the drug’s diffusion and dissolution,
with the drug release time prolonging, the mass fraction
of the unit of drugs in microspheres reduced, lead to the
release rate of drug that diffusion and degradation de-
crease, however, with the carrier material degrading and
the rate of degradation speeding up, the primarily release
of drug was degradation of materials, and made up the
rate of diffusion and dissolution release reducing, even-
tually led to the drug in microsphere carrier was release
in a constant velocity.
Solvent-control include of infiltration and swelling
mechanisms. 1) The release of solvent infiltration con-
trolled. It accord to the penetration principle of semi-
permeable membrane. Soluble drug is wrapped in poly-
mer, when it is added in environmental media, the ex-
ternal solvent go into polymer matrix by infiltration and
forms saturated solution and then under the action of
osmotic pressure between saturated solution and envi-
ronmental media to release drugs outside. 2) Matrix sol-
vent control, the more common mechanism is swelling.
The controlled-release mechanism is using solvent pene-
tration to makes polymer swelling and achieve the pur-
pose of release. At the beginning, solvent penetrate into
polymer matrix and cause to swelling, the polymer glass
transition temperature to the environment, and chemical
chain get slack, so that drugs can be released. Solvation
process often contains the spread process of drugs at the
same time.
The release of drug is affected by many factors and
conditions, including nature of polymer and drugs, tem-
perature of environment, pH value of medium and so on.
The change of one factor or condition will affect the
controlled mechanism of drug’s release. For example,
changing the hydrophilicity and hydrophobicity of de-
gradable polymer not only affect the rate of degradation
of materials, but also affect swelling and permeability of
the material, further affect the release of drugs.
Wang [38] prepared self-assembled nanomicelle of
N-acylcholesteryl succinate-O-carboxymethyl chitosan,
paclitaxel was used as a model drug. In vitro experiment,
they found that release rate of paclitaxel in nano-CCMC
micelle was closely related with the pH value. For ex-
ample the rate of release is low when the pH value of
PBS was equal to 7.2, but when pH value was equal to
4.0 or 9.0, the release rate increased. Because CCMC
molecules were a new type of polymer ampholyte and
containing much free-NH2 and-COOH, the isoelectric
point was about 7.14 by the turbidity method detection
[39]. In meta-acid or alkaline solution, the free-NH2
or-COOH in CCMC molecules was ionized to -NH +3
or-COO-. Under the action of charges with the same
electrical sign repel each other; the gel network structure
of self-assembled nano-micelles (CCMC) fully absorbed
water, increased permeability of paclitaxel, accelerated
the release rate.
Accordance to the interpretation of ISO meeting [40]:
biocompatibility means that the capability that the lives
tissue has a reaction to inactive materials. Generally re-
fers to the compatibility between materials and host,
including histocompatibility and blood compatibility.
Nano-bio-medical materials not only has the long-term
stable physical and mechanical properties in the bio-
logical conditions, but also has side effect to the organi-
zation, blood, immune system, etc, that is, non-toxic,
tissue compatibility, blood compatibility and so on. At
the same time biocompatibility is generally considered
to have two major principles, one is the principle of
‘biosafety’ and the second is the principle of ‘biofunc-
tionality’ (or the effect of promoting the function to the
body). Nano-biological materials are a foreign body for
46 Y. Liu et al. / Natural Science 2 (2010) 41-48
Copyright © 2010 SciRes. OPEN ACCESS
the host, so there will be some sort of response or repul-
sive phenomenon in the body. If nano-biological materi-
als could be applied successfully, at least, the response
that it caused should be acceptable by host, and
shouldn’t make harmful effects. So the biological mate-
rials should be carried on the evaluation of the nano-
bio-safety, that is, the biological evaluation. This is also
the key tache that if nano-biological material can enter to
clinical research [41]. So research about this area is ac-
tive. As early as 1999, Richardson, etc. [42] had been
studied the distribution of chitosan gene carriers in vivo.
Highly purified chitosan fractions of <5000 Da, 5000–
10000 Da and >10000 Daltons were prepared and char-
acterised in respect of their cytotoxicity, ability to cause
haemolysis, ability to complex DNA as well as to protect
DNA from nuclease degradation. The observations that
the highly purified chitosan fractions used were neither
toxic nor haemolytic, that they have the ability to com-
plex DNA and protect against nuclease degradation and
that low molecular weight chitosan can be administered
intravenously without liver accumulation suggest there is
potential to investigate further low molecular weight
chitosans as components of a synthetic gene delivery
system. Kim [43] synthesized biocompatible silica-
overcoated magnetic nanoparticles containing rhodamine
B isothiocyanate (RITC) within a silica shell of control-
lable thickness [MNPs@SiO2(RITC)]. In that study, the
MNPs@SiO2(RITC) with 50-nm thickness were used as
a model nanomaterial. After intraperitoneal administra-
tion of MNPs@SiO2(RITC) for 4 weeks into mice, the
nanoparticles were detected in the brain, indicating that
such nanosized materials can penetrate blood–brain bar-
rier (BBB) without disturbing its function or producing
apparent toxicity. After a 4-week observation, MNPs
@SiO2(RITC) was still present in various organs with-
out causing apparent toxicity. Through labeling with
rhodamine and got 50nm MNPs@ SiO2 (RITC). Taken
together, they demonstrated that magnetic nanoparticles
of 50-nm size did not cause apparent toxicity under the
experimental conditions of this study.
Yang [44] studied the distribution and toxicity of sili-
con nanoparticles in vivo. When silica nanoparticles
suspension injected in mice , after 96 h, electron mi-
croscopy result showed that silica nanoparticles distrib-
uted in the brain, liver, heart, spleen, lung, kidney,
stomach, intestines, prostate, testis and other organs, and
found a large quantity of silica nanoparticles had enter
into the cell nucleus of liver and a small amount that cell
nucleus of brain. Gave 4500 ug / kg nanoparticles to
mice through intraperitoneal injection, two weeks later,
there was no obvious abnormalities among mice body
weight, appetite, defecation when compared to the con-
trol group, none was dead. But some scholars also be-
lieve that when the particle size reduced to a certain de-
gree, the substance and material that original have
non-toxic or low toxic begin to appear toxicity or toxic-
ity significantly strengthened ; and nano-materials may
cause special situation of metabolism, have special tox-
Lam et al. [45] studied toxicity of carbon nanotubes to
the organisms. Compared with carbon black and quartz
(pink), carbon nanotubes (0.1-0.5 mg/kg) were injected
into rats through trachea. The result showed that the
group of carbon black rats was normal, the group of
quartz rats had mild to moderate inflammation, observed
lung epithelial granuloma in carbon nanotubes group and
had relationship with dose-response. These results show
that, if carbon nanotubes reach the lungs, they are much
more toxic than carbon black and can be more toxic than
quartz, which is considered a serious occupational health
hazard in chronic inhalation exposures. Service [46]
used polytetrafluorethylene (PTFE)-nano to do the inha-
lation contamination experiment on rat, the diameter of
PTFE-nano was 20 nm, the rats were contaminated 15
min, the majority of rats died within 4 h, but rats would
not be affected when the diameter was 130 nm. Yang [47]
studied the distribution of the original single-walled
carbon nanotubes in rats. They found carbon nanotubes
mainly distributed in the liver, lungs and spleen, and had
long residual time, minute quantity was excluded outer
the body through urine or feces. Though hadn’t found
acute toxicity reaction and allergic reaction, the chronic
toxicity of carbon nanotubes to the human body need to
be studied in-depth.
Because Nano-drug is a new type drug, the development
of nano-drug will cause the revolution of the diagnosis
and treatment. In recent years, nano-technology was
applied in traditional Chinese medicine and birth to the
new concept ‘nano Chinese medicine’. Among the active
ingredients of Chinese medicine, effective site, the
original drug, compound and new agents that using
nano-technology making has made some progress.
However, at present, the basic theory of nano-technology
appiled in medicine and the preparation of nano-drugs
are still incomplete, especially the safety of nano- medi-
cines has many problems remain to be explored in depth.
Therefore, the research in the field of nano-technology
appiled in medicine has a great deal of work needs to be
done, but the superior capability that nano-drugs owns
indicates a very wide range of applications in the clinical
disease treatment.
This work was jointly supported by the Scientific Innovation Project of
Northwest Normal University (Grant Nos: NWNU-KJCXGC-03-57,
NWNU-KJCXGC-03-49) and the Proficient Talent Project of lanzhou
Institute of Chemical Physics, Chinese Academy of Sciences (Grant
Y. Liu et al. / Natural Science 2 (2010) 41-48 47
Copyright © 2010 SciRes. OPEN ACCESS
No: 070430SRC1).
[1] Balogh, L.P. (2009) The future of nanomedicine and the
future of Nanomedicine: NBM. Nanomedicine, 5, 1.
[2] Shephard, M.J., Todd, D., Adair, B.M., Po, A.L.W.,
Mackie, D.P. and Scott, E.M. (2003) Immunogenicity of
bovineparainfluenza type 3 virus proteins encapsulated in
nanoparticle vaccines, following intranasal administra-
tion to mice. Res. Vet. Sci., 74, 187-190.
[3] Cui, Z.R.and Mumper, R.J. (2002) Intranasal administra-
tion of plasmid DNA-coated nanoparticles results in en-
hanced immune responses. J. Pharm. Pharmacol., 54,
[4] Vijayanathan, V., Thomas, T. and Thomas, T.J. (2002)
DNA nanoparticles and development of DNA delivery
vehicles for gene therapy. Biochemistry, 41,
[5] Cleland, J.L. (1998) Solvent evaporation processes for
the production of controlled release biodegradable mi-
crosphere formulations for therapeutics and vaccines.
Biotechnol. Prog., 14, 102-107.
[6] Esfand, R.and Tomalia, D.A. (2001) Poly (amidoamine)
(PAMAM) dendrimers:from biomimicry to drug delivery
and biomedical applications. Drug Discovery Today, 6,
[7] Aukunuru, J.V., Ayalasomayajula, S.P. and Kompella,
U.B. (2003) Nanoparticle formulation enhances the de-
livery and activity of a vascular endothelial growth factor
antisense oligonucleotide in human retinal pigment
epithelial cells. J. Pharm. Pharmacol., 55, 1199-1206.
[8] Maeda, H., Wu, J., Sawa, Y., Matsumura, Y. and Hori, K.
(2000) Tumor vascular permeability and the EPR effect
in macromolecular therapeutics:a review. J. Control. Re-
lease, 65, 271-284.
[9] Lukyanov, A.N. and Torchilin, V.P. (2004) Micelles from
lipid derivatives of water-soluble polymers as delivery
systems for poorly soluble drugs. Adv. Drug Delivery Rev.
56, 1273-1289.
[10] Torchilin, V.P. (2002) PEG-based micelles as carriers of
contrast agents for different imaging modalities. Adv.
Drug Delivery Rev., 54, 235-252.
[11] Mitra, S., Gaur, U., Ghosh, P.C. and Maitra, A.N. (2001)
Tumour targeted delivery of encapsulated dextran
doxorubicin conjugate using chitosan nanoparticles as
carrier. J. Control. Release, 74, 317-323.
[12] Du, S.L., Pan, H., Lu, W.Y., Wang, J., Wu, J. and Wang J.
Y. (2007) Cyclic Arg-Gly-Asp peptide-labeled liposomes
for targeting drug therapy of hepatic fibros is in rats. J.
Pharmacol. Exp. Ther., 322, 560-568.
[13] Briz, O., Macias, R.I.R., Vallejo, M., Silva, A., Serrano,
M.A. and Marin, J.J.G. (2003) Usefulness of liposomes
loaded with cytos tatic bile acid derivatives to circum-
vent chemotherapy res is tance of enterohepatic tumors.
Mol. Pharmacol., 63, 742–750.
[14] Saul, J.M., Annapragada, A.V. and Bellamkonda, R.V.
(2006) A dual-ligand approach for enhancing targeting
selectivity of therapeutic nanocarriers. J. Control. Re-
lease, 114, 277-287.
[15] Hashida, M., Akamatsu, K., Nishikawa, M., Yamashita,
F., Yoshikawa, H. and Takakura, Y. (2000) Design of
polymeric prodrugs of PGE1 for cell-specific hepatic
targeting. Pharmazie, 55, 202-205.
[16] Chung, J.E., Yokoyama, M., Aoyagi, T., Sakurai, Y. and
Okano, T. (1998) Effect of molecular architecture of hy-
drophobically modified poly (N-isopropylacrylamide) on
the formation of thermoresponsive core-shell micellar
drug carriers. J. Control. Release, 53, 119-130.
[17] Kohori, F., Sakai, K., Aoyagi, T., Yokoyama, M., Sakurai,
Y. and Okano, T. (1998) Preparation a characterization of
thermally responsive block copolymer micelles compris-
ing poly (N-isopropylacrylamide-β-DL-lactide). J. Con-
trol. Release, 55, 87-98.
[18] Meyer, O., Papahadjopoulos, D. and Leroux, J.C. (1998)
Co- polymers of N-isopropylacrylamide can trigger pH
sensitivity to stable liposomes. FEBS Lett. 421, 61-64.
[19] Stover, T.C., Kim, Y.S., Lowe, T.L. and Keste, M. (2008)
Thermoresponsive and bio-degradable linear-dendritic
nanoparticles for targeted and sustained release of a
pro-apoptotic drug. Biomaterials, 29, 359-369.
[20] Na, K., Lee, E.S. and Bae, Y.H. (2003) Adriamycin
loaded pullulan acetate/sulfonamide conjugate nanopar-
ticles responding to tumor pH: pH-dependent cell inter-
action, internalization and cytotoxicity in vitro. J. Con-
trol. Release, 87, 3-13.
[21] Yoo, H.S., Lee, E.A. and Park, T.G. (2002) Doxorubicin-
conjugated biodegradable polymeric micelles having
acid-cleavable linkages. J. Control. Release, 82, 17-27.
[22] Xiao S.Y., Tong, C.Y., Liu, X.M., Yu, D.M., Liu, Q.L.,
Xue, C.G., Tang, D.Y. and Zhao, L.J. (2006) Preparation
of folate-conjugated starch nanoparticles and its applica-
tion to tumor-targeted drug delivery vector. Chin. Sci.
Bull, 51, 1151-1155.
[23] Pan, J. and Feng, S.S. (2008) Targeted delivery of pa
clitaxel using folate-decorated poly(lactide)-vitaminE
TPGS nan-oparticles. Biomaterials, 29, 2663-2672.
[24] Terada, T., Iwai, M., Kawakami, S., Yamashita, F. and
Hashida, M. (2006) Novel PEG-matrix metalloprotei-
nase-2 cleavable peptide-lipid containing galactosylated
liposomes for hepatocellular carcinoma-selective target-
ing. J. Control. Release, 111, 333-342.
[25] Sershen, S.R., Westcoot, S.L., Halas, N.J. and West, J.L.
(2000) Temperature-sensitive polymer-nanoshell com-
posites for photothermally modulated drug delivery. J.
Biomed. Mater. Res., 51, 293-298.
[26] Sun, Y., Lu, M. and Yin, X.F. (2006) Ntracellular deliv-
ery of fluoresent dyes mediated by nanometer-liposomes.
Chem. J. Chin. U., 27, 632-634.
[27] Sivaramakrishnan, R., Nakamura, C., Mehnert, W., Kor-
ting, H.C., Kramer, K.D. and Schafer-Korting, M. (2004)
Glucocorticoid entrapment into lipid carriers-characteri-
zation by parelectric spectroscopy and influence on der-
mal uptake. J. Control. Release, 97, 493-502.
[28] Ding, J.C., Hu, F.Q. and Yuan, H. (2004) Uptake of
mono-stearin solid lipid nanoparticles by A549 cells.
Acta Phamaceutica Sinica, 39, 876-880.
[29] Pantarotto, D., Partidos, C.D., Hoebeke, J., Brown, F.,
Kramer, E., Briand, J.P., Muller, S., Prato, M. and Bianco,
A. (2003) Mmunization with peptide-functionalized car-
bon nanotubes enhances virus-specific neutralizing anti-
body responses. Chem. Biol., 10, 961-966.
48 Y. Liu et al. / Natural Science 2 (2010) 41-48
Copyright © 2010 SciRes. OPEN ACCESS
[30] Becker, M.L., Fagan, J.A., Gallant, N.D., Bauer, B.J.,
Bajpai, V., Hobbie, E.K., Lacerda, S.H., Migler, K.B. and
Jakupciak, J.P. (2007) Length-dependent up take of
DNA-wrapped single-walled carbon nanotubes. Adv.
Mater., 19, 939-945.
[31] Ito, Y., Venkatesan, N., Hirako, N., Sugioka, N. and Ta-
kada, K. (2007) Effect of fiber length of carbon nano-
tubes on the absorption of erythropoietin from rat small
intestine. Int. J. Pharm., 337, 357-360.
[32] Masaro, L. and Zhu, X.X. (1999) Physical models of
diffusion for polymer solutions, gels and solids. Prog.
Polymer Sci., 24, 731–775.
[33] Frank, A., Rath, S.K. and Venkatraman, S.S. (2005) Con-
trolled release from bioerodible polylners : effect of drug
type and polymer composition. J. Control. Release, 102,
[34] Du, Q., Hu, J.L., Han, Y.D., Chen, X.S. and Jing, X.B.
(2008) Preparation of controlled-release microspheres
loading protein through solid-in-oil-water emulsion
method. Chem. J. Chin. U., 29, l262-1266.
[35] Yang, Y.N., Lou, L., Liang, Q.Z., Chen, X.S. and Jing,
X.B. (2004) Preparation and in vitro release of rifampin
microspheres encapsulated in biodegradable polyesters.
Chem. J. Chin. U., 25, 162-165.
[36] Jain, R.A. (2000) The manufacturing techniques of vari-
ous drug loaded biodegradable poly(lactide-co-glycolide)
(PLGA) devices. Biomaterials, 21, 2475-2490.
[37] Wang, Y.M., Sato, H. and Horikoshi, I. (1997) In vitro
and in vivo evaluation of taxol release from
poly(lactic-co-glycolic acid) microspheres containing
isopropyl myri- state and degradation of the micro-
spheres. J. Control. Release, 49, 157-166.
[38] Wang, Y.S., Wang, Y.M., Li, R.S., Zhao, J. and Zhang,
Q.Q. (2008) Chitosan-based self-assembled nanomicelles
as a novel carrier for paclitaxel. Chem. J. Chin. U., 29,
1065- 1069.
[39] Li, J.H., Yu, Y.W., Yu, Y.L. and Shen, W. (2000) Studies
on preparation of carboxymethylchitosan. Chin. J. Bio-
chem. Pharmaceutics, 21, 175-177.
[40] Yang, X.F. and Xi, T.F. (2001) Progress in the studies on
the evaluation of biocompatibility of biomaterials. J.
Biomed. Eng., 18, 123-128.
[41] Fan, C.X. and Chen, L. (2004) Application of molecular
biological methods to the study of biomaterial evaluation.
Biomed. Eng.: Foreign Med. Sci., 27, 375-379.
[42] Richardson, S.C., Kolbe, H.V. and Duncan, R. (1999)
Potential of low molecular mass chitosan as a DNA de-
livery system: biocompatibility, body distribution and
ability to complex and protect DNA. Int. J. Pharm., 178,
[43] Kim, J.S., Yoon, T.J., Yu, K.N., Kim, B.G., Park, S.J.,
Kim, H.W., Lee, K.H., Park, S.B., Lee, J.K. and Cho,
M.H. (2006) Toxieity and tissue distribution of magnetie
nanopartieles in mice. Toxicol. Sci., 89, 338-347.
[44] Yang, J.Y., Chen, Y.X. and Zhang, Y.D. (2005) In vivo
distribution of silicon nanoparticles and toxicity tests,
China Medical Engineering. Chin. Med. Eng., 13,
[45] Lam, C.W., Jmes, J.T., McCluskey, R. and Hunter, R.L.
(2004) Pulmonary toxicity of single-wall carbon nano-
tubes in mice 7 and 90 days after intratracheal instillation.
Toxicol. Sci., 77, l26-134.
[46] Service, R.F. (2003) Nanomaterials show signs of toxic-
ity. Science, 300, 243.
[47] Yang, S.T., Guo, W., Lin, Y., Deng, X. Y., Wang, H. F.,
Sun, H.F., Liu, Y.F., Wang, X., Wang, W., Chen, M.,
Huang, Y.P. and Sun, Y.P. (2007) Biodistribution of pris-
tine single-walled carbon nanotubes in vivo. J. Phys.
Chem. C, 111, 17761-17764.