Presentation: Hydrogel

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Presentation: Hydrogel

  1. 1. Name: Sayyad Ali Presented To Dr. Taos Khan Topic # Hydrogel Dated 27/02/1202 COMSATS ABBOTTABAD. 1
  2. 2. Hydrogel Introduction The method by which a drug is delivered can have a significant effect on its efficacy. Some drugs have an optimum concentration range within which maximum benefit is derived, and concentrations above or below this range can be toxic or produce no therapeutic benefit at all. 2
  3. 3. • To minimize drug degradation and loss, to prevent harmful side-effects and to increase drug bioavailability and the fraction of the drug accumulated in the required zone, various drug delivery and drug targeting systems are currently under development 3
  4. 4. • Among drug carriers one can name soluble polymers, micro particles made of insoluble or biodegradable natural and synthetic polymers, Microchips, microcapsules, cells, cell ghosts,lipoproteins, liposome’s, and micelles. The carriers can be made slowly degradable, stimuli-reactive (e.g., pH or temperature-sensitive), and even targeted. 4
  5. 5. • Hydrogels are water-swollen polymeric materials that maintain a distinct three- dimensional structure. Their classification may be based on the source: natural, synthetic, or hybrid hydrogels (composed of synthetic and natural molecules); on the basis of nature of the crosslinking: covalent or non-covalent (physical) gels; 5
  6. 6. • On the basis of nature of the network: homopolymer, copolymer, interpenetrating, or double networks; physical structure: (optically transparent), microporous, and macroporous hydrogels, and on their fate in the organism: degradable and non-degradable hydrogels. Due to their high water content, most hydrogel structures possess excellent biocompatibility. 6
  7. 7. • There is a wide variety of the design options for the preparation of hydrogels of different structures and properties. The traditional methods of hydrogel synthesis were limited in the control of their detailed structure, but novel approaches based on genetic engineering and hybrid hydrogels, have considerably enhanced this research. 7
  8. 8. • As a result, the application potential of hydrogels, in addition to traditional areas such as biomaterials and drug delivery systems, has expanded to other fields, such as microfluidics and nanotechnology. 8
  9. 9. DISCOVERY• In the early 1950s Otto and Lím from the Prague(Czechoslovakia) Institute of Chemical Technology initiated a research program to design polymers for medical use. Some merchandised polymers had been applied in humans use previously, but this was the first attempt to design polymers for human use with properties to fulfill the criteria of biocompatibility. 9
  10. 10. • The target was the design of new biomaterials for applications in ophthalmology. The main features of their design were (included in their grant proposal in 1952 which stated as• (a)shape stability and softness similar to that of the soft surrounding tissue;• (b) chemical and biochemical stability; 10
  11. 11. • c) high permeability for water-soluble nutrients and metabolites across the biomaterial tissue-interface.• It is amazing that these hypotheses are still valid for soft contact lenses. 11
  12. 12. • Based on this validation, Lím started efforts to synthesize new hydrogels. First, he considered polymerization of N-vinylpyrrolidone. However, it was not available, so Lim’s first experiments focused on partially methacryloylation of polyvinylalcohol. Polyvinylalcohol was chosen due to its previous use in human implants (Ivalon et al). 12
  13. 13. • Methacryloyl esters were chosen because the structure of the polymer reflects a pivalic (trimethyl acetic acid) acid structure. The latter was known to be stable to pure hydrolysis. 13
  14. 14. • The polyvinyl alcohol route produced optically clear hydrogels containing 80–90% water but these hydrogels did not show mechanical properties necessary for use in contact lenses. 14
  15. 15. gelatine hydrogels crosslinked with partiallyoxidised dextrans. 15
  16. 16. 16
  17. 17. • One year later, Lím by chance identified a novel hydrogel material. He was synthesizing the tri ethylene glycol di methacrylate monomer by acid catalyzed trans esterification of methyl methacrylate with tri ethylene glycol. 17
  18. 18. • At the end of the reaction he come across with the neutralization of the acid, dilution with water to isolate the water-insoluble tri ethylene glycol di methacrylate, washing the organic layer with water, drying and isolating the pure product by distillation. 18
  19. 19. • (One day Lím had to catch the train to his home, so he stopped the reaction early, and managed to add water to separate the layers before leaving. In the morning, he noticed that the water layer turned into a clear hydrogel overnight). 19
  20. 20. • Obviously, it was a copolymer of tri- ethylene-glycol, mono-methacrylate with tri-ethylene-glycol di- methacrylate led to the final selection of a hydrogel. 20
  21. 21. • So the existence of hydrogels dates back to 1960, when Otto and Lim first proposed the use of hydrophilic networks of poly- hydroxyl-ethyl methacrylate (PHEMA) in contact lenses.• Since then, the use of hydrogels has extended to various biomedical and pharmaceutical applications. 21
  22. 22. • In comparison to other synthetic biomaterials, hydrogels resemble living tissues closely in their physical properties because of their relatively high water content , soft and rubbery consistency.• Hydrogels show minimal tendency to adsorb proteins from body fluids because of their low interfacial tension. 22
  23. 23. • Further, the ability of molecules of different sizes to diffuse into (drug loading) and out of (drug release) hydrogels allows the possible use of dry or swollen polymeric networks as drug delivery systems for oral, nasal, buccal, rectal, vaginal, ocular and parenteral routes of administration. 23
  24. 24. Hydrogel can be delivered by any of the following routs 24
  25. 25. • Because of these qualities it gained different names like ‘intelligent gels’ or ‘smart hydrogels. The smartness of any material is the key to its ability to receive, transmit or process a stimulus, and respond by producing a useful effect. 25
  26. 26. Hydrogels are ‘smart’ or ‘intelligent’ in thesense that they can recognize thepredominant stimuli and respond bydisplaying changes in their physical orchemical behavior, resulting in the release ofentrapped drug in a controlled manner. 26
  27. 27. • Some hydrogels undergo continuous or discontinuous changes in swelling that are mediated by external stimuli such as changes in pH, temperature, ionic strength, solvent type, electric and magnetic fields, light, and the presence of chelating species. 27
  28. 28. • The majority of stimuli responsive hydrogels were created using conventional (traditional) methods of synthesis of a relatively small number of synthetic polymers, especially (meth) acrylate derivatives and their copolymers. 28
  29. 29. • In 1968, Dusek and Patterson theoretically predicted that changes in external conditions might result in abrupt changes of the hydrogel’s degree of swelling.• Indeed, 10 years later, Tanaka and others have verified the theory by experimental observations 29
  30. 30. Pathways of solid polymer degradation(General) 30
  31. 31. Cont.… pathways of degradation 31
  32. 32. Basic difference in gel and hydrogel• Both gels and hydrogels might be similar chemically, but they are physically distinct.• D. Jordan suitably described gels as ‘The colloidal condition, the gel, is one which is easier to recognize than to define • Technically, gels are semi-solid systems comprising small amounts of solid, dispersed in relatively large amounts of liquid, having more solid-like than liquid-like character. Sometimes, hydrogels are also described as aqueous gels because of the prefix ‘hydro’. 32
  33. 33. • Although the term ‘hydrogel’ implies a material already swollen in water, while in a true sense hydrogel is a cross-linked network of hydrophilic polymers. They possess the ability to absorb large amounts of water and swell, while maintaining their three- dimensional (3D) structure. 33
  34. 34. • hydrogels display swelling in aqueous media for the same reasons that an analogous linear polymer dissolves in water to form an ordinary polymer solution. Thus, the feature central to the functioning of a hydrogel is its inherent cross-linking.• Conventional gels can also develop small levels of cross-links as a result of a gain in energy under the influence of shear forces, but these are reversible 34
  35. 35. • Because of the above quality hydrogels is a polymer network, these polymers produce systems that extend a range of rigidities, beginning with a sol and increasing to jelly, gel and hydrogel. Thus, hydrogel, sometimes referred to as xerogel, is a more rigid form of gel 35
  36. 36. Future perspectives• An interesting characteristic about many responsive hydrogels is that the mechanism causing changes in network structure can be entirely reversible in nature.• This conveys elastic deformability with ‘shape-memory’ behaviors so that hydrogels return back to their original shape at the end of initiating stimuli. 36
  37. 37. • Keeping in view this quality The Jiang’s laboratory developed a tunable (adjustable) liquid lens that permits autonomous focusing. The design was based on a temperature-sensitive hydrogel. 37
  38. 38. • All the scientific evidences seem to indicate that the basic and translational research in hydrogels has a bright future.• Numerous new designs, e.g. involving protein domains containing non-recognized amino acids, successful attempts has done to control the morphology of self-assembling peptide fibers, artificial glycoproteins for controlling cell responses , hydrogels play a key role in the building material for the microchemotaxis and for all the above phenomena. 38
  39. 39. • It has a role in the enhancement of the use of DNA recognition motifs, and an improved synthetic method can be established with hydrgel(Genetic Engineering).• An outstanding example of the potential of stimuli-sensitive hydrogels in the development of bionanotechnology products is the design of optical systems that do not require mechanical components. 39
  40. 40. Application of hydrogel• New researchers have demonstrated that a gel composed of small, woven protein fragments can successfully carry and release proteins of different sizes to different targets in the body.• It is enabling the delivery of drugs such as insulin and trastuzumab (A monoclonal antibody (protein) often used to treat breast and ovarian cancer), hormones, growth factors as well as eye medications. 40
  41. 41. • Furthermore, one can control the rate of release of active ingredients from hydrogel by changing the density of the gel, allowing for continuous drug delivery over a specific period of time.• A newly introduced gel, known as a "nanofiber hydrogel scaffold," enables, over hours, days or even months, a gradual release of the proteins from the gel, and the gel itself is eventually broken down into harmless amino acids (the building blocks of proteins). 41
  42. 42. • Peptide hydrogels are ideally suited for drug delivery as they are pure, easy to design and use, non-toxic, bio-absorbable, and can be locally applied to a particular tissue.• Depending on the size and density of the mesh, it can carry protein molecules between 14,000 and 150,000 daltons (a unit of molecular weight).• Earlier work showed that the hydrogels could also carry smaller molecules, between 300 and 900 daltons. " So it can deliver both small molecules and big molecules,". 42
  43. 43. REFERENCES1. Kopeček J, Yang J. Polymer Int. 2007;56:1078–1098.2. Dušek K, Prins W. Adv Polym Sci. 1969;6:1–102.3. Wichterle O. Encyclopedia of Polymer Science and Technology. In: Mark HF, Gaylord NG, Bikales N, editors. Interscience. Vol. 15.New York, NY: 1971. pp. 273–291.4. Andrade JD, editor. Hydrogels for Medical and Related Applications. ACS Symposium Series. Vol. 31. Washington D.C: 1976.5. Ratner BD, Hoffman A. Hydrogels for Medical and Related Applications. In: Andrade JD, editor. ACS Symposium Series. Vol. 31.Washington D.C: 1976. pp. 1–36.6. Kůdela V. In: Encyclopedia of Polymer Science and Engineering. Mark HF, Kroschwitz J, editors. Wiley; New York, NY: 1987. pp.783–807.7. Peppas NA, editor. Hydrogels in Medicine and Pharmacy. I–III. CRC Press; Boca Ratyon, FL: 1987.8. Brøndsted H, Kopeček J. Polyelectrolyte Gels. In: Harland RS, Prud’homme RK, editors. ACS Symposium Series. Vol. 480.Washington D.C: 1992. pp. 285–304.9. Kamath KR, Park K. Adv Drug Delivery Rev. 1993;11:59–83.10. Osada Y, Gong J. Prog Polym Sci. 1993;18:187–226.11. Peppas NA, Bures P, Leobandung W, Ichikawa H. Eur J Pharmaceutics Biopharm. 2000;50:27–46.12. Hoffman AS. Adv Drug Delivery Rev. 2002;54:3–12.13. Nayak S, Lyon LA. Angew Chem Int Ed. 2005;44:7686–7708.14. Lím, D., Personal communication, 2001.15. Lím D. RNDr Thesis. Technical University Prague; 1953.16. Grindlay JH, Clagett OT. Proc Staff Meet Mayo Clin. 1949;24:538.17. Wichterle O, Lím D. Nature. 1960;185:117–118.18. Kopeček J, Lím DJ. Polym Sci Part A-1. 1971;9:147–154.19. Dreifus M, Klenka L. Československá oftalmologie (in Czech) 1959;15:95–101.20. Dreifus M, Wichterle O, Lím D. Československá oftalmologie (in Czech) 1960;16:154–159.21. Dreifus M, Herben T, Lím D, Wichterle O. Sb Lék (In Czech) 1960;62:212–218. 43
  44. 44. 22. Wichterle O. Original Czech version (“Vzpomínky”) in 1992. 1994. Recollections.23. Wichterle O. Czechoslovak Academy of Sciences. U.S. Patents. 3,660,545; 3,408,429; 3,496,254;3,499,86224. Wichterle O. In: Soft Contact Lenses. Ruben M, editor. Wiley; New York: 1978. pp. 3–5.25. Wichterle O. Czechoslovak Academy of Sciences. U.S. Patents. 3,361,858; 3,497,577; 3,542,90726. It was an interesting time to be a graduate student in the early 60s at IMC Prague. In addition tobeing exposed to an exciting new research field, it was possible to witness soccer and movie starsvisiting Prof. Wichterle and trying to get a free sample of soft contact lenses that were not commerciallyavailable at that time.27. Kolařík J, Migliaresi CJ. Biomed Mater Res. 1983;17:757–767.28. Tighe BJ. In: Hydrogels in Medicine and Pharmacy. Peppas NA, editor. III. CRC Press; BocaRaton, Florida: 1987. pp. 53–82.29. Nicolson PC, Vogt J. Biomaterials. 2001;22:3273–3283. [PubMed]30. Krejčí L, Harrison R, Wichterle O. Arch Ophthal. 1970;84:76–80. [PubMed]31. Křístek A, König B, Wichterle O. Klin Abl Augenheilk (in German) 1966;149:219–227.32. Kresa Z, Rems J, Wichterle O. Arch Otholaryngol. 1973;17:360–365.33. Hubáček J, Wichterle O, Kliment K, Hubáček Jar, Dušek J. Československá otolaryngologie (inCzech) 1968;17:211–215.34. Šprincl L, Vacík J, Kopeček J, Lím D. J Biomed Mater Res. 1971;5:197–205. [PubMed]35. Kopeček J, Šprincl L, Bažilová H, Vacík J. J Biomed Mater Res. 1973;7:111–121. [PubMed] Thank you 44

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