Untitled

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.
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SAFETY DATA SHEET PRODUCT ID: LIDOCAINE HYDROCHLORIDE AND EPINEPHRINE INJECTION SECTION 1: PRODUCT AND COMPANY IDENTIFICATION Lidocaine hydrochloride 2% and Epinephrine 1:50,000 Injection Lidocaine hydrochloride 2% and Epinephrine 1:100,000 Injection OCTOCAINE® 50 (Lidocaine Hydrochloride 2% and Epinephrine 1:50, 000 Injection) LIGNOSPAN® FORTE (Lidocaine Hydrochloride

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