Vol.1, No.2, 67-75 (2009)
Copyright © 2009 Openly accessible at http://www.scirp.org/journal/HEALTH/
Electrospun nanofiber-based drug delivery systems
Deng-Guang Yu1, Li-Min Zhu1*, Kenneth White2, Chris Branford-White2
1College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China
2Institute for Health Research and Policy, London Metropolitan University, London, UK
Received 15 May 2009; revised 8 June 2009; accepted 11 June 2009.
Electrospinning is a very simple and versatile
process by which polymer nanofibers with di-
ameters ranging from a few nanometers to sev-
eral micrometers can be produced using an
electrostatically driven jet of polymer solution
or polymer melt. Significant progress has been
made in this process throughout the past few
years and electrospinning has advanced its ap-
plications in many fields, including pharmaceu-
tics. Electrospun nanofibers show great prom-
ise for developing many types of novel drug
delivery systems (DDS) due to their special
characteristics and the simple but useful and
effective top-down fabricating process. The
current state of electrospun nanofiber-based
DDS is focused on drug-loaded nanofiber
preparation from pharmaceutical and biode-
gradable polymers and different types of DDS.
However, there are more opportunities to be
exploited from the electrospinning process and
the corresponding drug-loaded nanofibers for
drug delivery. Additionally, some other related
challenges and the possible resolutions are
outlined in this review.
Keywords: Electrospinning; Nanofibers; Drug Delivery
Systems; Controlled Release
Electrospinning, firstly reported in 1934, has been used
for more than 60 years, and yet is under developed in
studying the fabrication of continuous nanofibers. The
term “electrospinning”, derived from “electrostatic spin-
ning”, was coined relatively recently. Since 1980s and
especially in recent years, the electrospinning process
has regained more attention probably due in part to a
surging interest in nanotechnology, as ultrafine fibers or
fibrous structures of various polymers with diameters in
the submicron/nanometer range can be easily fabricated
using this process. A survey of open publications and
patents related with electrospinning in the past several
years is given in Figure 1 The data were obtained from
Elsevier ScienceDirect, Wily InterScience and the
Dewent Innovations Index, and clearly demonstrates that
electrospinning has attracted increasing attention in re-
cent times. [1-3]
A schematic diagram demonstrating the process of
electrospinning of polymer nanofibers is shown in
Figure 2. There are basically three components: a high
voltage supplier, a capillary tube with a pipette or needle
of small diameter, and a metal collecting screen. In elec-
trospinning a high voltage is used to create an electri-
cally charged jet of polymer solution or melt out of the
pipette. Before reaching the collecting screen, the solu-
tion jet evaporates or solidifies, and is collected as an
interconnected web of small fibers. One electrode is
placed into the spinning solution/melt and the other at-
tached to the collector. In most cases, the collector is
simply grounded. The electric field is applied across the
end of the capillary tube that contains the solution fluid
held by its surface tension. This induces a charge on the
surface of the liquid. Mutual charge repulsion and the
contraction of the surface charges to the counter elec-
trode create a force directly opposite to the surface ten-
sion. As the intensity of the electric field is increased, the
hemispherical surface of the fluid at the tip of the capil-
lary tube elongates to form a conical shape known as the
Taylor cone. Further increasing the electric field, a criti-
cal value is attained with which the repulsive electro-
static force overcomes the surface tension and the
charged jet of the fluid is ejected from the tip of the
Taylor cone. The discharged polymer solution jet un-
dergoes an instability and elongation process, which
allows the jet to become very long and thin. Meanwhile,
the solvent evaporates, leaving behind a charged poly-
mer fiber. In the case of the melt the discharged jet so-
lidifies when it travels in the air stream. [2-12]
Electrospinning appears to be affected by the follow-
ing parameters and variables: 1) system parameters such
as molecular weight, molecular weight distribution and
architecture (branched, linear, etc.) of the polymer, and
polymer solution properties (viscosity, conductivity, di-
electric constant, and surface tension, charge carried by
the spinning jet) and 2) process parameters such as
D. G. Yu et al. / HEALTH 1 (2009) 67-75
Openly accessible at
Figure 1. The increase of literature electrospinning from sev-
eral databases (Search term is “electrospinning” within “source
Figure 2. The process of electrospinning.
electric potential, flow rate and concentration, distance
between the capillary and collection screen, ambient
parameters (temperature, humidity and air velocity in the
chamber) and finally motion of the target screen. By
appropriately varying one or more of the above parame-
ters, nanofibers can be successfully electrospun from a
rich variety of materials that include polymers, biopoly-
mers, DNA, protein, composites, and ceramics and even
relatively small macromolecules such as phospholipids.
A number of processing techniques such as drawing,
template synthesis, phase separation and self-assembly
have been used to prepare polymer nanofibers in recent
years. However these methods have disadvantages such
as: material limitation, they are time-consuming and they
require complicated processing systems. As far as elec-
trospinning is concerned it is not only a simple one-step
top-down process for fabricating nanofibers, but also the
co-processing of polymer mixtures, chemical cross-
linking can be carried out that provide a variety of path-
ways for controlling the chemical composition of the
nanofibers. These provide a wide range of properties
such as strength, weight, elasticity, porosity and charged
surface areas. Moreover electrospinning also provides
the capacity to lace together a variety of nanoparticles or
nanofillers types that can be encapsulated into a nanofi-
ber matrix. Functional micro/nano particles may be dis-
persed in polymer solutions, which are then electrospun
to form composites in the form of continuous nanofibers
and nanofibrous assemblies. All these endow electro-
spinning with outstanding manufacturing capabilities but
utilizing an easy process and capable of excellent flexi-
bility. Additionally, electrospinning seems to be the only
method that can be further developed for mass produc-
tion of one-by-one continuous nanofibers from various
polymers. [3]
Over the past several decades, polymer sciences have
been the backbone of pharmaceutics [13]. Many phar-
maceutical polymer excipients are commonly used in the
development of novel drug delivery systems (DDS) now.
Combined usage of electrospinning with pharmaceutical
polymers provides novel strategies for developing novel
DDS, and through the manipulation of electrospinning
process, may offer flexibility for tailoring DDS’s proper-
Polymer nanofibers have a diameter in the order of a few
nanometers to over 1 μm (more typically 50~500 nm)
and possess unique characteristics, such as: extraordi-
nary high surface area per unit mass (for instance, nano-
fibers with ~100 nm diameter have a specific surface of
~1000m2/g), coupled with remarkably high porosity,
excellent structural mechanical properties, high axial
strength combined with extreme flexibility, low basis
weight, and cost effectiveness are among others.
Another interesting aspect of using nanofibers is that
it is feasible to modify not only their morphology and
their (internal bulk) content but also the surface structure
to carry various functionalities. Nanofibers can be easily
post-synthetically functionalized (for example by che-
mical or physical vapour deposition). Furthermore, it is
even feasible to control secondary structures of nanofi-
bers in order to prepare nanofibers with core/sheath
structures, nanofibers with hollow interiors and nanofi-
bers with porous structures. [10]
Economically, the electrospinning nano-manufactur-
ing process is relatively low cost compared to that of
most bottom-up nanofiber-fabricating methods. The re-
sulting nanofibers are often uniform, continuous and do
not require expensive purification protocols. The nano-
fibers are relatively easy to be scaled up for productivity
due to the top-down process and the designing of multi-
ple jets for synchronous electrospinning. [14] Addition-
ally, the nanofibers have one dimension at the micro-
scopic scale but another dimension macroscopically.
This unique characteristic endows nanofiber mats with
both the merits possessed by functional materials on the
nano-meter scale, and these have advantages over con-
ventional solid membrane such as easy processing, ease
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of packaging and shipping.
These outstanding properties make polymer nanofi-
bers as good candidates for many applications. For ex-
ample nanofibers mats are now being considered for
composite materials reinforcement, sensors, filtration,
catalysis, protective clothing, biomedical applications
(including wound dressing and scaffolds for tissue engi-
neering, implants, membranes and drug delivery sys-
tems), space applications such as solar sails, and micro-
and nanooptoelectronics. Thus the properties of nanofi-
bers make them useful for systems for developing nano-
fibers-based DDS.
Research about electrospun nanofibers as drug delivery
systems is in the early stage of exploration. [3] Many
current researches focus on the preparation and charac-
terization of polymer nanofibers. To date, it is generally
believed that nearly one hundred different polymers,
mostly dissolved in solvents yet some heated into melts,
have been successfully spun into ultrafine fibers. How to
transit nanofibers into DDS is creating much attention. It
is clear from Figure 3 that the open publications related
to electrospun nanofiber-based DDS are increasing more
sharply than those related with nanofibers.
The first report about electrospinning fibers as DDS
was noted by Kenawy et al. [5] Electrospun fiber mats
were explored as drug delivery vehicles using tetracy-
cline hydrochloride as a model drug. The mats were
made either from poly (lactic acid) (PLA), poly (ethyl-
ene-co-vinyl acetate) (PEVA), or from a 50:50 blend of
the two from chloroform solutions. Release profiles
showed promising results when they were compared to a
commercially available DDS--Actisite® (Alza Corpora-
tion, Palo Alto, CA), as well as to the corresponding cast
films. An early patent registered by Ignatious and
Baldoni described electrospun polymer nanofibers for-
pharmaceutical compositions, which can be designed to
provide rapid, immediate, delayed, or modified dissolu-
tion, such as sustained and/or pulsatile release character-
istics. [6]
Later studies on the preparation of nanofibers from
polymers with different drug-loaded capabilities and the
corresponding DDS were reported, such as transdermal,
fast dissolving and implantable DDS (Figure 4). Most of
the early work focused on the sustained release profiles
and all types of active pharmaceutical ingredients were
used as model drugs, such as small molecular drug,
herbs, proteins, poorly water-soluble and water-soluble
drugs, DNA, genes and vaccines. The polymers include
biodegradable hydrophilic polymers, hydrophobic poly-
mers and amphiphilic polymers. [3,15,16]
Zhang et al. reported that degradable heparin-loaded
poly (ε-caprolactone) fiber mats were successfully fab-
ricated by electrospinning. The highly sulphated heparin
hetropolymer remained homogenous in the spinning
solution and was evenly distributed throughout the fab-
ricated polymers. A sustained release of heparin could be
achieved from the fibers over 14 days with the release
diffusionally controlled over this period. The released
heparin retained biological properties and functionality.
[17] Chew et al. investigated the feasibility of encapsu-
lating human β-nerve growth factor (NGF) that was sta-
bilized in the carrier protein, bovine serum albumin
(BSA) in a copolymer of ε-caprolactone and ethyl eth-
ylene phosphate. Partially aligned protein encapsulated
fibers were obtained and the protein was found to be
randomly dispersed throughout the electrospun fibrous
mesh in an aggregated form. The sustained release of
NGF by diffusion was obtained for at least 3 months.
PC12 neurite outgrowth assay confirmed that the bioac-
tivity of electrospun NGF was retained throughout the
period of sustained release. [18] Luu et al. utilized elec-
trospinning to fabricate synthetic polymer/DNA compos-
ite for therapeutic application in gene delivery designed
for tissue engineering. The composite was non-woven,
nano-fibered, membranous structures composed pre-
dominantly of poly(lactide-co-glycolide) (PLGA) random
Figure 3. The increase of literature about e-spinning nanofi-
bers as DDS (Search term is “electrospinning” in “title and
“drug delivery” in “abstract”).
Figure 4. Applications and preparations of electrospun drug-
loaded nanofibers.
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copolymer and a poly(D,L-lactide)–poly(ethylene glycol)
(PLA– PEG) block copolymer. Release of plasmid DNA
from the composite was sustained over a 20-day study
period, with maximum release occurring at ~2 h. Cumu-
lative release profiles indicated amounts released were
approximately 68–80% of the initially loaded DNA.
Results indicated that DNA released directly from these
electrospun fibers was indeed intact, capable of cellular
transfection, and successfully expressed the encoded
protein β-galactosidase. [19]
Electrospun nanofibers are often used to load insolu-
ble drugs for enhancing their dissolution properties due
to their high surface area per unit mass. Tungprapa et al.
prepared ultra-fine fiber mats of cellulose acetate (CA)
for four different types of model drugs, i.e., naproxen
(NAP), indomethacin (IND), ibuprofen (IBU), and su-
lindac (SUL), from 16% w/v CA solutions in 2:1 v/v
acetone/N,N-dimethylacetamide (DMAc) by electro-
spinning. The amount of the drugs in the solutions was
fixed at 20 wt% based on the weight of CA powder. No
drug aggregates were observed on the surfaces of the
fibers. The maximum release of the drugs from loaded
fiber mats were ranked as follows: NAP>IBU>IND>
SUL and this did not correspond to their solubility prop-
erties. [7] Taepaiboon et al. reported that the molecular
weight of the model drugs played a major role on both
the rate and the total amount of drugs released from the
prepared drug-loaded electrospun PVA nanofibers. The
rate and the total amount of the drugs released decreas-
ing with increasing molecular weight of the encapsulated
drugs. [8]
Taepaiboon et al. also reported that mats of PVA nan-
ofibres were successfully prepared by the electrospin-
ning process and were developed as carriers of drugs for
a transdermal drug delivery system. Besides the water
insoluble drugs naproxen (NAP), and indomethacin
(IND), freely water soluble sodium salicylate, was also
spun into the PVA fibers. [8] Xu et al. proposed a novel
process, i.e., ‘emulsion electrospinning’ to prepare
core-sheath fibers to incorporate a water soluble drug
into a hydrophobic or an amphiphilic polymer fiber. [20]
Maretschek et al. [21] recently reported the electrospin-
ning of emulsions composed of an organic poly (L-lac-
tide) solution and an aqueous protein solution, which
yielded protein containing nanofiber nonwovens having
a mean fiber diameter of approximately 350 nm. This
provided the opportunity to tailor the release profile of
macromolecular active ingredients. All the above reports
demonstrated that electrospun drug-loaded nanofibers
were able to provide sustained release profiles for dif-
ferent types of active pharmaceutical ingredients.
Studies previously reported the influence of a high
electrical potential on the chemical integrity of the drugs,
the comparatively controlled release characteristics of
nanofibers and the release-controlled mechanisms.
Tungprapa et al. [7] and Taepaiboon et al. [8] confirmed
that the electrospinning process did not affect the
chemical integrity of the drugs by 1H-nuclear magnetic
resonance. Taepaiboon et al. [8] proved that the
drug-loaded electrospun PVA mats exhibited better re-
lease characteristics of four model drugs than drug-
loaded as-cast films and Tungprapa et al. [7] showed that
the release of drugs from the CA drug- loaded films was
due mainly to the gradual dissolution of aggregates on
the film surfaces, whilst the diffusion of the drugs in-
corporated within the films occurred to a lesser extent.
On the contrary, since no presence of the drug aggre-
gates was found on the surface of the drug-loaded CA
fibers, the release of the drugs from the drug-loaded fi-
ber mats was mainly by the diffusion of the drugs from
the fibers, as the fiber mats could swell appreciably in
the testing medium. Moreover the fibrous morphology of
the drug-loaded fiber mats after the drug release assay at
24h was still intact. Verreck et al. confirmed that the
application of electrostatic spinning to pharmaceutical
applications resulted in dosage forms with better useful
and controllable dissolution properties than the simple
physical mixture, solvent cast or melt extruded samples.
Although many types of DDS have been prepared
from electrospun drug-loaded nanofibers, no related
clinical experiments have been reported and only few in
vivo drug delivery researches have been undertaken,
which were mainly associated with the cancer research.
Ranganath et al. reported the paclitaxel-loaded biode-
gradable implants in the form of microfiber discs and
sheets developed using electrospinning were used to
treat malignant glioma in vitro and in vivo. The fibrous
matrices not only provided greater surface area to vol-
ume ratio for effective drug release rates but also pro-
vided needed implantability into the tumor resected cav-
ity of a post-surgical glioma. [23]
The advantages of employing electrospinning tech-
nology to prepare DDS are not as yet fully exploited.
Nanotechnology is now having an impact in biotechnol-
ogy, pharmaceutical and medical diagnostics sciences.
Nanodrugs are at the forefront of bioengineering for
diseases and represent the next generation of medical
therapies that will impact worldwide markets and espe-
cially the healthcare industry [24]. Furthermore electro-
spinning as noted before has gained more attention due
in part to a surging interest in nanotechnology, as ul-
trafine fibers or fibrous structures of various polymers
with small diameters. [25] On the other hand, electro-
spinning should exert more influence on new DDS de-
velopment through providing novel strategies for con-
ceiving and fabricating them.
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From the current literature, several advantages of using
electrospun polymer nanofibers as DDS are recognized,
and these merit further consideration in developing new
types of DDS.
Firstly, due to the high surface area to volume ratio,
polymer nanofibers provide a useful pathway for deliv-
ery of water insoluble drug. With the recent advent of
high throughput screening of potential therapeutic agents,
the number of poorly soluble drug candidates has risen
sharply and the formulation of poorly soluble com-
pounds for oral delivery now presents one of the most
frequent and greatest challenges to formulation scientists
in the pharmaceutical industry. [26] Solid dispersion is
considered to be the most suitable choice to improve
dissolution rates and hence the bioavailability of the
poorly water soluble drug. [27] However, the practical
applicability of solid dispersion systems has remained
limited due to difficulties in conventional methods of
preparation, poor reproducibility of physiochemical
properties, dosage formulation and lack of feasibility for
scaling-up manufacturing processes. [28] Electrospun
nanofibers may provide novel approaches as to how the
dissolution rate of even very poorly soluble compounds
might be improved to minimize the limitations of oral
Xie et al. developed electrospun PLGA-based nanofi-
bers as implants for the sustained delivery of anticancer
drug to treat C6 glioma cells in vitro. Differential scan-
ning calorimetry (DSC) results suggest that the drug was
in the solid solution state in the polymeric micro- and
nanofibers. In vitro release profiles suggest that pacli-
taxel sustained release was achieved for more than 60
days. Cytotoxicity test results suggest that the IC50 value
of paclitaxel-loaded PLGA nanofibers is comparable to
the commercial paclitaxel formulation-Taxol®. [29]
Figure 5. Fast dissolving drug delivery membrane.
Verreck and co-workers assessed the application of
water-soluble polymer-based nanofibers prepared by
electrostatic spinning as a means of altering the dissolu-
tion rate of the poorly water-soluble drug, itraconazole.
DSC measurements found that the melting endotherm
for itraconazole was not present, suggesting the forma-
tion of an amorphous solid dispersion or solution. Dis-
solution studies assessed several presentations including
direct addition of the non-woven fabrics to the dissolu-
tion vessels, folding weighed samples of the materials
into hard gelatin capsules and placing folded material
into a sinker. [22] Studies in our laboratory have been
undertaken on the solubility improvement of poorly wa-
ter-soluble drugs and the corresponding fast dissolving
DDS. [30] Shown in Figure 5 is a patent product of a
rapid dissolving drug delivery membrane, which can
absorb water and dissolve within several seconds a
poorly water-soluble drug.
Second, the drug release profile can be easily finely
tailored by modulation not only of the composition of
the nanofiber mats but also the morphology of nanofi-
bers, the process and the micro-structure. Core-sheath
structure is a very useful structure for all kinds of appli-
cations. Several fabrication techniques have been pro-
posed to prepare ultrafine fibers configured in a
core-sheath structure, such as self-assembly, laser abla-
tion, template synthesis, and a tube by fiber templates
process. Core-sheath fibers can be prepared by ‘emul-
sion electrospinning’. Xu et al. [16] reported that uni-
form core-sheath nanofibers were prepared by electro-
spinning a water-in-oil emulsion in which the aqueous
phase consists of a poly(ethylene oxide) (PEO) solution
in water and the oily phase is a chloroform solution of an
amphiphilic poly(ethylene glycol)-poly(L-lactic acid)
(PEG-PLA) diblock copolymer. The obtained fibers are
composed of a PEO core and a PEG-PLA sheath with a
sharp boundary in between. By adjusting the emulsion
composition and the emulsification parameters, the
overall fiber size and the relative diameters of the core
and the sheath can be altered. The stretching and evapo-
ration induced de-emulsification and the transformation
from the emulsion to the core-sheath fibers.
Concentric electrospinning is a very promising ap-
proach to fabricate core-sheath fibers. [31] Coaxial elec-
trospinning (Figure 6) is an alternative approach to en-
capsulate drugs or biological activties inside polymer
nanofibers. In a typical process (Figure 6), two or more
polymer liquids are forced by an electrostatic potential to
eject out through different but co-axial capillary chan-
nels, resulting in a core-shell structured composite nano-
fiber. As long as the shell fluid is able to be processed
along with electrospinning, the core fluid can either be
or not be electrospinnable. One advantage in using such
a technique is an effective protection of easily denatured
biological agents and the potential to wrap all substances
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Figure 6. Co-axial electrospinning systems.
in the core regardless of drug-polymer interactions.
Hence, drugs, proteins, growth factors, and even genes
can be incorporated into nanofibers by dissolving them
in the core solutions. [32-34]
Huang et al. used co-axial electrospinning to prepare
core-sheath nanofibers for controlled release of multi
drugs. Polycaprolactone was used as the shell and two
medically pure drugs, Resveratrol and Gentamycin Sul-
fate, were used as the cores. The drugs were released in
a controlled way without any initial burst effect. [32]
Third, there is a lot of flexibility in the use of nanofi-
bers in designing various dosage forms to achieve
maximum bioavailability of a drug moiety for different
drug delivery routes. Electrospun drug-loaded nanofibers
are often used as mid dosage forms. They can be further
turned into different kinds of DDS for all types of drug
delivery routes, such as for transdermal administration,
oral administration, pulmonary administration, subcuta-
neous implant, or for dissolution into a liquid media for
administration, such as a suspension or solution or by
parenteral/intramuscular or intracavernosum injection
and so on. [35]
Besides preparing DDS solely from electrospun fibers,
researchers often combine the electrospinning process
with other special substances to prepare DDS. Shalaby
describes a partially absorbable, fiber-reinforced com-
posite in the form of a ring, or a suture-like thread, with
modified terminals for use as a controlled delivery sys-
tem of bioactive agents. The composite comprised an
absorbable fiber construct capable of providing time-
dependent mechanical properties of a biostable elas-
tomeric matrix containing an absorbable microparticu-
late ion-exchanger to modulate the release of the bioac-
tive agents for a desired period of time at a specific bio-
logical site, such as the vaginal canal, peritoneal cavity,
scrotum, prostate gland, an ear loop or subcutaneous
tissue. [36]
Fourth, electrospun nanofibers often have higher drug
encapsulation efficiency than other nanotechnologies.
Xie et al. reported that the encapsulation efficiency for
paclitaxel-loaded PLGA micro- and nanofibers was more
than 90%. The electrospun paclitaxel-loaded biodegrad-
able micro- and nanofibers are promising for the treat-
ment of brain tumour as alternative drug delivery de-
vices. [29] Xu et al. showed that a water-soluble anti-
cancer agent, doxorubicin hydrochloride, was totally
encapsulated within the electrospun poly (ethylene gly-
col)-poly (l-lactic acid) (PEG-PLLA) fibers when its
content in the fibers was 5 wt %. [37] Other advantages
of drug-loaded nanofibers, such as small diameter of the
nanofibers, can provide short diffusion passage length.
Also, high surface area facilitates mass transfer and ef-
fective drug release.
As mentioned above, the drug-loaded nanofibers de-
rived from electrospinning not only have one dimension
at the microscopic scale but another dimension in the
macroscopic form. This unique characteristic endows the
electrospun drug-loaded nanofibers with both the merits
possessed by the DDS on the nano-meter scale in alter-
ing the biopharmaceutic and pharmacokinetic properties
of the drug molecule for favorable clinical outcomes,
and also the advantages of conventional solid dosage
forms such as easy processing, good drug stability, and
ease of packaging and shipping.
Although some reports in the literature have demon-
strated that electrospinning is useful for preparing new
DDS there are still some challenges associated with the
preparation of electrospun nanofiber-based DDS.
Electrospinning is a simple micro-processing tech-
nique to make ultrafine or nanometer range fibers gener-
ally from high molecular weight polymer solutions or
melts. The largest challenge lies firstly in understanding
the electrospinning process as a fluid dynamics system.
In order to control the properties, geometry, and mass
production of the nanofibers, it is necessary to under-
stand quantitatively how electrospinning transforms the
fluid solution through a millimeter diameter capillary
tube into solid fibers which are four to five orders
smaller in diameter. Secondly, the efficiency of electro-
spinning is still a bottleneck. Studies on multiple nozzles
need to be undertaken and these will form a platform for
electrospinning industrialization. [38-40]
To date, most of the release tests have been done in
vitro. What is more, several problems must be resolved
for further applications such as the drug loading, the
initial burst effect, the residual organic solvent, the sta-
bility of active agents, and the combined usage of new
biocompatible polymers. Drug-loading is always a prob-
lem for nano DDS. Although drug loading over 50% of
the total weight was reported, the drug loading in the
nanofibers still needs to be increased in many cases. The
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D. G. Yu et al. / HEALTH 1 (2009) 67-75
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reason is that drug often influences the spinnability of
the polymer solution. The viscosity range of a polymer
solution which is spinnable is about 1–20 poises and the
surface tension between 35 and 55 dynes/cm is suitable
for fiber formation. Relatively high drug loading may
also easily cause the uneven distribution of the drug in
the nanofiber resulting in initial burst effects for elec-
trospinning fibers except for co-axial fibers. [41]
The initial burst effect is a common phenomenon for
nano drug delivery systems with high surface area such
as nano- or microspheres, liposomes and hydrogels. The
reason for this phenomenon has been investigated by a
number of laboratories. For ordinary electrospinning,
drug-loaded nanofibers electrospun from mixtures of
drugs and polymers the drug release characteristics rely
on the drug being encapsulated within the nanofibers.
However due to surface effects the drug particles in the
nanofibers tend to accumulate on the fiber surface. Thus,
a burst release at an initial stage is inevitable unless the
blend of drug and polymer carrier is fully integrated into
the nanofiber at a molecular level. [32]
Zeng et al. studied the encapsulation of the lipophilic
drug paclitaxel and the hydrophilic drug doxorubicin
hydrochloride in the electrospun PLLA fiber mats and
their release kinetics. Preferable encapsulation of pacli-
taxel was found due to its good compatibility with PLLA
and solubility in chloroform/acetone solvent, whereas
doxorubicin hydrochloride was observed on or near the
surfaces of PLLA fibers. The release results of these
drugs confirmed that the release of paclitaxel from elec-
trospun PLLA fiber samples followed nearly zero-order
kinetics due to the degradation of the fibers. However a
burst release was found for doxorubicin hydrochloride
due to the diffusion of the drug on or near the surfaces of
the fiber sample. Therefore, the solubility and compati-
bility of the drugs in the drug/polymer/solvent system
were the decisive factors for the preparation of the elec-
trospun fiber formulation with constant release of the
drugs. In order to encapsulate a majority of the drugs
inside the polymer fibers and thus to acquire a constant
and stable drug release profile, a lipophilic polymer
should be chosen as the fiber material for a lipophilic
drug while a hydrophilic polymer should be employed
for a hydrophilic drug and the solvents used should be
suitable for both drug and polymer. [41]
To smoothen or even eliminate the initial burst effects,
post-treatment methods are often considered. Within this
context Kenawy et al. reported that the burst release of
ketoprofen was eliminated when the electrospun
poly(vinyl alcohol) fiber mats were stabilized against
disintegration in water by treatment with methanol. [5]
Taepaiboon post-treated electrospun fibre mats of
poly(vinyl alcohol) (PVA) containing sodium salicylate
by exposing the fibre mats to the vapour from 5.6 M
aqueous solution of either glutaraldehyde or glyoxal for
various exposure time intervals, followed by a heat
treatment in a vacuum oven. With increasing the expo-
sure time in the cross-linking chamber, the morphology
of the electrospun fiber mats gradually changed from a
porous to a dense structure. Cross-linking appreciably
reduced the release of sodium salicylate from the
drug-loaded fiber mats and both the rate and the total
amount of the drug released decreased functions with
exposure time interval in the cross-linking chamber. [42]
Certainly, the core-shell structure fiber with the drug
in the core can eliminate the burst effects. Research also
showed that surfactants can reduce the surface tensions
and the diameter of resulted nanofibers, improve the
drug uniformity and thus can smoothen the burst effect.
To adapt the development of pharmaceutics, one of
the emphases is the preparation of novel polymers
drug-loaded nanofibers, for example, polymer with en-
vironmental sensitive characteristics. Chunder et al. re-
ported that ultrathin fibers comprising two oppositely
charged weak polyelectrolytes PAA/PAH were fabri-
cated using electrospinning. These fibers are capable of
controlling drug releasing through pH changes. The re-
leasing properties of PAA/PAH fibers was tuned by de-
positing different coatings onto fiber surfaces. A sus-
tained and a temperature controlled drug releasing in
PBS solutions was achieved by depositing perfluorosi-
lane coatings and PAA/PNIPAAM multilayers onto the
fiber surfaces, respectively. [44]
In theory, comprehension and clarification of the rela-
tionship between the release profiles and the electro-
spinning parameters help to select suitable materials,
optimize electrospinning process, and thus to improve
the consistence between design and manufacturing, re-
duce the time to market for novel DDS. Since the physi-
cal form of the active agent in a dosage form can influ-
ence the product performance, it is often necessary to
quantify the different solid phases in a system for pre-
paring a robust dosage form. In nanofibers, the possible
interactions between the drugs and the excipients in the
dissolution and electrospinning processes should be
thoroughly investigated for further developing novel
Drug release profiles from the drug delivery systems
should be precisely predicted or programmed so that any
possibility of dose dumping and subject-to-subject vari-
ability can be minimized. The relationships between the
drug controlled release profile and the electrospinning
parameters should be elucidated. Mathematical models
of drug release from nanofibers can be used to elucidate
the underlying drug transport mechanism and predict the
resulting drug release kinetics as a function of the nano-
fibers (structure, geometry and composition). In conclu-
sion, there are still many things to do to enable the elec-
trospun nanofiber-based DDS to go into clinical applica-
SciRes Copyright © 2009
D. G. Yu et al. / HEALTH 1 (2009) 67-75
Openly accessible at
We thank the UK-CHINA Joint Laboratory for Therapeutic Textiles
and Biomedical Textile Materials, China Postdoctoral Science Founda-
tion (NO.20080440565), and Grant 08JC1400600 from Science and
Technology Commission of Shanghai Municipality for the financial
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