Nanofiber for drug delivery system – principle and application by R.Rathinamoorthy, Department of Fashion Technology, PSG College of Technology, India. Abstract: The use of nanotechnology in the textile industry has increased rapidly due to its unique and valuable properties. Electrospinning is a novel process for producing superfine nanofibers. Special properties make them suitable for a wide range of applications from medical to consumer products and industrial to high-tech applications. This paper details the different nanofiber manufacturing methods and its pro and cons. Further it explores the different principles of drug delivery and the application of nanofiber in pharmaceutical Drug Delivery System (DDS). Keywords: Nanofiber, Self-assembly, Phase Separation, Electro Spinning, Drug Loading, Drug Delivery. Introduction Self-assembly Electrospinning
otechnology is defined as the utilization of
nents into an ordered and stable structure
fibers of diameters ranging from 10 nm to
has been known since 1934, when the first
material, devices or systems with novel or
patent on electrospinning was filed.
into patterns or structures without human
polymer melt or solution16. A majority of
nature and technology11. Self-assembly of
the published work on electrospinning has
between physics, chemistry and biology.
spinning rather than on melt electrospin-
requirements and the difficulty in produc-
applications such as medical, filtration,
barrier, wipes, personal care, composite,
Spinning
garments, insulation, and energy storage.
the process of electrospinning of polymer
dures and extremely elaborate techniques.
nanofibers is shown in Figure 1. There are
high pore volume, and tight pore size are
The low productivity of the self-assembly
basically three components: a high voltage
the characteristics of the nanofiber2-3.
supplier, a capillary tube with a pipette or
needle of small diameter, and a metal col-
Phase separation
fibers. These Special properties make them
used to create an electrically charged jet of
suitable for a wide range of applications
rich domain and a solvent-rich domain, of
screen, the solution jet evaporates or solid-
ifies, and is collected as an interconnected
energy storage, fuel cells, and information
technology4. In this report, the first phase
ning solution/melt and the other attached
polymer scaffolds. Phase separation can be
to the collector. Another interesting aspect
of using nanofibers is that it is feasible to
by adding nonsolvent to the polymer solu-
Delivery System (DDS), which includes the
modify not only their morphology and their
tion, thus called thermal induced or non-
(internal bulk) content but also the surface
structure to carry various functionalities.
respectively. Polymer scaffolds obtained by
the different applications of nanofiber as
ranging from 50 nm to 1000 nm or greater17
Nano fibers
is a simple technique that does not require
much specialized equipment. It is also easy
to achieve batch-to-batch consistency, and
phase separation, and electrospinning5-7.
tailoring of scaffold mechanical properties
and architecture is easily achieved by vary-
simple and efficient. Electrospinning as a
involving electrospinning first appeared in
polymers and is strictly a laboratory scale
potential to a polymeric solution18. A wide
Table 1: Nanofiber manufacturing methods – merits and demerits
range of polymers has been used to electro-
Lab/ Industrial
spin nanofibers. Natural polymers such as
Advantages Limitations application processing
collagen, gelatin, chitosan, hyaluronic acid,and silk fibroin have been used to produce
nanofibers that can form potential scaffolds
for tissue engineering applications. More
recently, nanofibers of protein have been
demonstrated to have promising use in tissue
engineering19. The unique properties of elec-
trospun mats – high specific surface area and
properties, pore size Matrix directly fabricated.
small pores are very favorable for the adsorp-
tion of liquids and for preventing bacteria
tions for wound healing. The simplicity allows
for electrospinning to be the only nanofi-
brous processing technique that can be taken
out of a laboratory setting and be utilized
successfully in scale-up and mass production.
The following table explains the merits and
demerits of different nanofiber manufactur-ing methods20.
electrospinning). These techniques can be
medical and biotechnological applications
used to give finer control over drug release
nanofibers, the likely modes of the drug in
has some intrinsic advantages. From a bio-
the resulting nanostructed products are28:
logical point of view, a great variety of nat-
1. Drug as particles attached to the sur-
ural biomaterials are deposited in fibrous
Principle
forms or structures. polymer nanofibers can
provide a proper route to emulate or dupli-
cate biosystems—a biomimetic approach.
based on the principle that dissolution rate of
a drug particulate increases with increased
have shown evidences that apart from sur-
surface area of both the drug and the corre-
face chemistry, the nanometer scale surface
sponding carrier if necessary. For controlled
3. The blend of drug and carrier materials
drug delivery, in addition to their large surface
tant effect on regulating cell behavior in
area to volume ratio, polymer nanofibers also
Spinning
terms of cell adhesion, activation, prolifera-
have other additional advantages. For exam-
4. The carrier material is electrospun into
tion, alignment and orientation. The bio-
ple, unlike common encapsulation involving,
tissue engineering, controlled drug release,
improve the therapeutic efficacy and safety of
drugs by delivering them to the site of action
Mechanism of drug delivery
implants, nanocomposites for dental appli-
at a rate dictated by the need of the physio-
cations, molecular separation, biosensors
logical environment. A wide variety of poly-
and preservation of bioactive agents.
meric materials have been used as delivery
vide insight into the direct incorporation of
matrices, and the choice of the delivery vehi-
bioactive growth factors into scaffolds. Nanofibers for controlled
cle polymer is determined by the require-
Additionally, drug delivery systems can be
drug delivery
ments of the specific application24. Polymeric
combined with implantable tissue engineering
nanofibers have recently been explored for
scaffolds to prevent infection while repair and
their ability to encapsulate and deliver bioac-
regeneration occur. Biodegradable polymers
agents to patients in a most physiologically
tive molecules for therapeutic applications.
release drug in one of two ways29: erosion and
diffusion. Release from biodegradable poly-
Drug loading
mers in vivo is governed by a combination of
both mechanisms, which depends on the rel-
amount of drug efficiently, precisely and for
ative rates of erosion and diffusion.
tic drugs into nanofibers involves solubiliz-
a defined period of time. New technologies
ing the drug into the polymer solution to
and materials will have a profound impact
drug delivery are degraded by hydrolysis.
on drug delivery. Either biodegradable or
Hydrolysis is a reaction between water mole-
control whether drug release occurs via dif-
typically ester bonds, which repeatedly cuts
fusion alone or diffusion and scaffold degra-
the polymer chain until it is returned to
dation. Additionally, due to the flexibility in
material selection a number of drugs can be
are enzymatically degradable, which is also a
delivered including: antibiotics, anticancer
type of chain scission. As water molecules
drugs, proteins, and DNA. Using the various
electro spinning techniques a number of dif-
chain, the physical integrity of the polymer
burst release may also be indicative of the
ferent drug loading methods can also be uti-
degrades and allows drug to be released. The
drug being attached only on the surface.
different mechanisms were given below29. Types of drug release
compared to non-degradable materials,which tend to release drug primarily by dif-
In general a few typical different types of
fusion. Generally it is desirable to design a
release can be recognised relevant in textile
drug delivery device that gives controlled
drug delivery systems; immediate release,
release of the desired agent; however, this
extended release and triggered or delayed
release The different mechanisms are 30,31.
degrading as the drug is being released. Immediate release
This type of release is required in situ-
from chloroform solutions. Release profiles
reaching toxic levels. Thus, special care
compared to a commercially available DDS--
rate and the degradation rate if a degrad-
Actisite® (Alza Corpora-tion, Palo Alto, CA).
Extended release
finely tailored by modulation not only of
spinning for pharmaceutical application.
the composition of the nanofiber mats but
be designed as rapid, immediate, delayed,
sheath structure is a very useful structure
polymer carrier used. It was found that the
for all kinds of applications. Xu et al.32
tively smooth release of drug over a period
nanofibers were prepared by electro-spin-
of five days. In a different report 35, bioab-
Triggered or delayed release
ning a water-in-oil emulsion in which the
aqueous phase consists of a poly(ethylene
poly(lactic acid) was used for loading an
oxide) (PEO) solution in water and the oily
antibiotic drug mefoxin. The efficiency of
Spinning
amphiphilic poly(ethylene glycol)-poly(L-
bulk film was demonstrated. For potential
lactic acid) (PEG-PLA) diblock copolymer.
drugs loaded in water-soluble and wateri-
were investigated. It was shown that drug
a specific event, situation, or change in
fication parameters, the overall fiber size
loaded polymer nanofibers by electrospin-
and the relative diameters of the core and
the sheath can be altered. Different release
would facilitate the drug dissolution.
drug delivery device a number of require-
Application
ments must be met. As with materials used
in tissue engineering applications, materials
scaffolds produced by electrospinning for
that undergo biodegradation are generally
fibers as DDS was noted by Kenawy et al.33
the delivery of water-insoluble drugs such
more popular due to the fact that they elim-
Electrospun fiber mats were explored as drug
as intraconazole and ketanserin. In their
inate the need for explantation. However,
biodegradable materials add an extra level
nanodispersion of the waterinsoluble drug
of complexity to drug delivery devices as
nanofibers from polymers with differentdrug-loaded capabilities and the corre-sponding DDS were reported, such astransdermal, fast dissolving andimplantable DDS. Electrospun nanofibersare often used to load insoluble drugs forenhancing their dissolution properties dueto their high surface area per unit mass. Taepaiboon et al. reported that the molec-ular weight of the model drugs played amajor role on both the rate and the totalamount of drugs released from the pre-pared drug-loaded electrospun PVAnanofibers. The rate and the total amountof the drugs released decreasing with
Figure 2: Different mechanism of drug release.
hydrochloride from electrospun poly(ethyl-
ene-co-vinylacetate), poly(lactic acid), and a
Publishers, Stevenson Ranch, CA, 2005, pp.
blend. J.Contr. Release 81, 57, 2002.
26. Thanou, M., and Duncan, R. Polymer-pro-
tein and polymer-drug conjugates in cancer
preparing artificial threads. U.S. patent
therapy. Curr. Opin. Invest.Drugs 4, 701,
S. Zhang, Fabrication of novel biomaterials
27. Jiang, H., Fang, D., Hsiao, B., Chu, B., and
Chen, W. Preparation and characterization of
Biotechnology 21 (2003) 1171–1178.
10. J.D. Hartgerink, E. Beniash, S.I. Stupp,
glycolide)/poly(ethylene glycol)-g-chitosan
Peptide-amphiphile nanofibers: a versatile
electrospun membranes. J. Biomater. Sci.
Figure 4: Applications and preparations of
scaffold for the preparation of self-assem-
electrospun drug- loaded nanofibers36.
bling materials, Proceedings of the National
Academy of Sciences of the United States of
increasing molecular weight of the encap-
Antonios G. Mikos,. “Electrospinning of
sulated drugs38. Verreck et al. confirmed
Polymeric Nanofibers for Tissue Engineering
11. Whitesides, G.M., and Grzybowski, B. Self-
that the application of electrostatic spin-
Applications: A Review”, Tissue Engineering,
assembly at all scales. Science 295, 2419,
resulted in dosage forms with better useful
12. Chiti, F., Stefani, M., Taddei, N., Ramponi,
than the simple physical mixture, solvent
effect of mutations on peptide and protein
Engineering and technology”, CRC Press,
aggregation rates. Nature 424, 805, 2003.
13. Hua, F.J., Kim, G.E., Lee, J.D., Son, Y.K., and
Taylor & Francis Group, 2007, ISBN-10: 0-8493-7563-0.
Lee, D.S. Macroporous poly(L-lactide) scaf-fold Preparation of a macroporous scaffold
30. Uekama, K., Hirayama, F. and Irie, T. (1998),
by liquid–liquid phase separation of a PLLA–
dioxane–water system. J. Biomed. Mater.
spinning technology to prepare DDS are not
31. L. Van Langenhove, “Smart textiles for medi-
as yet fully exploited. Nanotechnology is
14. Nam, Y.S., and Park, T.G. Biodegradable
cine and healthcare”, Woodhead Publishing
polymeric microcellular foams by modified
Limited, 2007. ISBN-13: 978-1-84569-027-4.
pharmaceutical and medical diagnostics sci-
thermally induced phase separation method.
32. Xu, X., Chen, X., Wang, Z. and Jing, X.
ences. Furthermore electro-spinning as noted
(2009) Ultrafine PEG–PLA fibers loaded with
before has gained more attention due in part
15. V.J. Chen, P.X. Ma, Nano-fibrous poly(-lactic
both paclitaxel and doxorubicin hydrochlo-
acid) scaffolds with interconnected spherical
ride and their in vitro cytotoxicity, Euro. J.
to a surging interest in nanotechnology, as
macropores, Biomaterials 25 (2004) 2065–
ultrafine fibers or fibrous structures of various
33. Kenawy, E.R., Bowlin, G.L., Mansfield, K.,
16. Yury Gogotsi, “ Nano Material Hand Book” ,
Layman, J., Simpson, D.G., Sanders, E.H.,
Spinning
other hand, electro-spinning should exert
and Wnek, G.E. (2002) Release of tetracy-
cline hydrochloride from electrospun poly
through providing novel strategies for con-
(ethylene-co-vinylacetate), poly(lactic acid),
ceiving and fabricating them. Still several
Electrospinning. Nanotechnology, 7:216–23
and a blend, J. Control. Release, 81, 57-64.
problems must be resolved for further appli-
18. Hohman Mm, Shin M, Rutledge G, Et Al.
34. F.Ignatious and J. M. Baldoni, Electrospun
cations such as the drug loading, the initial
Forced Jets. Ii Applications. Phys Fluids,
burst effect, the residual organic solvent, the
35. Zong, K. Kim, J . Chiu, B. S . Hsiao, B. Chu, S
stability of active agents, and the combined
19. Rajesh Vasita, Dhirendra S Katti, “
. Li, B. Garlick, C. Brathwaite, T. Zimmerman
Nanofibers and Their Applications In Tissue
and D. Fang, Polym. Prepr. 44(2) (2003) 89. References
White, Chris Branford-White, “Electrospun
20. Catherine P. Barnes a, Scott A. Sell a, Eugene
nanofiber-based drug delivery systems”,
D. Boland a, David G. Simpson b, Gary L.
“Introduction to Nanotechnology”, ISBN 0-
Bowlin a, “Nanofiber technology: Designing
471-07935-9. John Wiley & Sons, Inc 2003.
the next generation of tissue engineering
K. E. Drexler “Engines of Creation”, Fourth
37. Verreck G, Chun I, Rosenblatt J, Et Al. 2003b.
scaffolds ”, Advanced Drug Delivery Reviews
R.Rathinamoorthy, M.sumothi, “Innovative
State Into Electrospun Nanofibers Composed
Application of Nano Fiber”, Textile Asia, Jan
22. R. G. Flemming, C. J . Murphy, G. A.
Abrams, S . L. Goodman And P . F . Nealey,
Advancements In Electrospun Nanofibers.”
spun mats of poly(vinyl alcohol) fi-bres and
Symposium of Processing and Fabrication of
“Electrospinning: Applications in drug deliv-
their release characteristics of four model
Advanced Materials, Ed Ts Srivatsan & Ra
ery and tissue engineering” Biomaterials 29
39. Verreck, G., Chun, I., Peeters, J., Rosenblatt,
24. Heller J, Hoffman As. 2004. Drug Delivery
J. and Brew-ster, M. E. (2003) Preparation
polymer nanofibers, Journal of Nanoscience
System. In Ratner Bd, Hoffman, As, Schoen
and characterization of nanofibers contain-
and Nanotechnology 4 (2004) 52–65.
ing amorphous drug dispersions gen-erated
L.A. Smith, P.X.Ma, Nano-fibrous scaffolds
Introduction to Materials In Medicine. 2nd
by electrostatic spinning, Pharm Res, 20,
for tissue engineering, Colloids and Surfaces.
Ed. San Diego: Elsevier Academic Pr. P 629–
B, Biointerfaces 39 (2004) 125–131.
40. Rutledge, G.C. and Fridrikh, S.V. (2007)
X. Wen, D. Shi, N. Zhang, Applications of
25. Kenawy, E.R., Bowlin, G.L., Mansfield, K.,
Formation of fibers by electrospinning, Adv.
nanotechnology in tissue engineering, in: H.
Layman, J., Simpson, D.G., Sanders, E.H.,
Fiscal Federalism in Mexico: Distortions and Structural Traps Enrique Cabrero Mendoza*1 The decentralization process in Mexico has shown significant progress by trying to empower local and state governments. However, the Mexican case makes clear that the transfer of greater powers to subnational governments does not necessarily means an increase in their institutional capacities. Th