Polymers in Medicine

Polim. Med.
Index Copernicus (ICV 2022) – 121.55
MEiN – 70
Average rejection rate – 39.13%
ISSN 0370-0747 (print)
ISSN 2451-2699 (online) 
Periodicity – biannual

Download PDF

Polymers in Medicine

2014, vol. 44, nr 2, April-June, p. 119–127

Publication type: review article

Language: Polish

Wykorzystanie pokryć z poli(glikolu etylenowego) i chitozanu do zapewnienia biokompatybilności nanocząstkom w aplikacjach biomedycznych

The Use of Shells Made of Poly(Ethylene Glycol) and Chitosan to Ensure the Biocompatibility of Nanoparticles in Biomedical Applications

Tomasz Kubiak1,

1 Zakład Fizyki Medycznej, Uniwersytet Adama Mickiewicza w Poznaniu, Poznań, Polska

Streszczenie

Biomedyczne aplikacje nanocząstek wymagają, aby struktury te charakteryzowały się szeroko pojętą biokompatybilnością. Najlepszym sposobem na jej osiągnięcie jest zastosowanie pokrycia z odpowiedniego polimeru, który pozwoli zmienić właściwości powierzchniowe rdzenia nanocząstek. Otoczki tworzy się z materiałów biodegradowalnych tak, by produkty rozkładu mogły być łatwo eliminowane z organizmu. Opłaszczenie nanocząstek pozwala na zwiększenie ich stabilności (zarówno w roztworach wodnych, jak i w krwiobiegu), przeciwdziała aglomerowaniu, zapewnia hydrofilowość powierzchni oraz pozwala na dołączanie do niej różnych cząsteczek, np. leków lub ligandów kierujących, stosowanych w terapii celowanej nowotworów. Polimerowe pokrycie wpływa też w istotny sposób na zmniejszenie toksyczności nanocząstek i ich interakcje z różnymi typami komórek. Do opłaszczania nanostruktur często wykorzystuje się chitozan i poli(glikol etylenowy) (PEG) ze względu na ich dostępność i korzystne właściwości. Ogromną zaletą PEG jest jego zdolność do wydłużania czasu cyrkulacji wprowadzonych do krwiobiegu nanocząstek przez zapobieganie ich opsonizacji i ograniczenie wychwytu przez makrofagi. Chitozan ze względu na swój dodatni ładunek silnie oddziałuje z błonami komórkowymi i powierzchniami śluzowymi, co może być przydatne w systemach dostarczania leków. Należy jednak pamiętać, iż masa molowa oraz stopień deacetylacji użytego chitozanu znacząco wpływają na jego charakterystykę. Opłaszczanie nanostruktur jednocześnie poli(glikolem etylenowym) i chitozanem bądź też pokrywanie ich nowymi kopolimerami na bazie PEG ma na celu dalszą optymalizację właściwości nośników nanocząsteczkowych, aby zwiększyć ich bezpieczeństwo i niezawodność w zastosowaniach biomedycznych.

Abstract

Biomedical applications of nanoparticles require that these structures are characterized by broadly defined biocompatibility. The best way to achieve this goal is to use an appropriate polymer coating, which can modify the surface properties of the nanoparticles core. The shells are formed from biodegradable material, so that the products of their decomposition can be easily eliminated from the body. Coating of nanoparticles allows to increase their stability (both in aqueous solutions and in the bloodstream), prevents agglomeration, provides the hydrophilicity of the surface and allows to attach various molecules such as drugs and tumor targeting ligands in cancer therapy. The polymer coating significantly affects the reduction of toxicity of nanoparticles and their interactions with different cell types. Chitosan and poly(ethylene glycol) (PEG) are frequently used for coating of nanostructures due to the availability and favourable properties. A major advantage of PEG is its ability to prolong the circulation time of nanoparticles injected into the bloodstream by preventing their opsonization and reducing the uptake by macrophages. Chitosan, because of its positive charge, strongly interacts with cell membranes and mucosal surfaces, which can be useful in drug delivery systems. However, it should be remembered that the molar mass and the degree of deacetylation of the used chitosan significantly affect its characteristics. The use of combined shells made of poly(ethylene glycol) and chitosan or coatings formed from new PEG based copolymers aims at further optimization of the properties of nanoparticle carriers to increase their safety and reliability in biomedical applications.

Słowa kluczowe

PEG, chitozan, nanocząstki, biokompatybilność, terapia celowana

Key words

PEG, chitosan, nanoparticles, biocompatibility, targeted therapy

References (43)

  1. Naahidi S., Jafari M., Edalat F., Raymond K., Khademhosseini A., Chen P.: Biocompatibility of engineered nanoparticles for drug delivery. J. Control. Release 2013, 166, 182–194.
  2. Filippousi M., Papadimitriou S.A., Bikiaris D.N., Pavlidou E., Angelakeris M., Zamboulis D., Tian H., Van Tendeloo G.: Novel core–shell magnetic nanoparticles for Taxol encapsulation in biodegradable and biocompatible block copolymers: Preparation, characterization and release properties. Int. J. Pharm. 2013, 448, 221–230.
  3. Rodrigues S., Dionisio M., López C.R., Grenha A.: Biocompatibility of Chitosan Carriers with Application in Drug Delivery. J. Funct. Biomater. 2012, 3, 615–641.
  4. Tan W.B., Zhang Y.: Surface modification of gold and quantum dot nanoparticles with chitosan for bioapplications. J. Biomed. Mater. Res. Part A 2005, 75, 56–62.
  5. Sahay G., Alakhova D.Y., Kabanov A.V.: Endocytosis of nanomedicines. J. Control. Release 2010, 145, 182–195.
  6. Li S.D., Huang L.: Stealth nanoparticles: High density but sheddable PEG is a key for tumor targeting. J. Control. Release 2010, 145, 178–181.
  7. Köseoglu Y., Yildiz F., Kim D.K., Muhammed M., Aktas B.: EPR studies on Na-oleate coated Fe3O4 nanoparticles. Phys. Stat. Sol. (C). 2004, 1, 3511–3515.
  8. Huang M., Khor E., Lim L.Y.: Uptake and Cytotoxicity of Chitosan Molecules and Nanoparticles: Effects of Molecular Weight and Degree of Deacetylation. Pharm. Res. 2004, 21, 344 –353.
  9. Zhang M., Li X.H., Gong Y.D., Zhao N.M., Zhang X.F.: Properties and biocompatibility of chitosan films modified by blending with PEG. Biomaterials 2002, 23, 2641–2648.
  10. Majeti N.V., Kumar R.: A review of chitin and chitosan applications. React. Funct. Polym. 2000, 46, 1–27.
  11. Molinaro G., Leroux J.C., Damas J., Adam A.: Biocompatibility of thermosensitive chitosan-based hydrogels an in vivo experimental approach to injectable biomaterials. Biomaterials 2002, 23, 2717–2722.
  12. Schipper N.G.M., Varum K.M., Artursson P.: Chitosans as Absorption Enhancers for Poorly Absorbable Drugs. 1: Influence of Molecular Weight and Degree of Acetylation on Drug Transport Across Human Intestinal Epithelial (Caco-2) Cells. Pharm. Res. 1996, 13, 1686–1692.
  13. Vauthier C., Zandanel C., Ramon A.L.: Chitosan-based nanoparticles for in vivo delivery of interfering agents including siRNA. Curr. Opin. Colloid Interface Sci. 2013, 18, 406–418.
  14. Shi S.F., Jia J.F., Guo X.K., Zhao Y.P., Chen D.S., Guo Y.Y., Cheng T., Zhang X.L.: Biocompatibility of chitosan-coated iron oxide nanoparticles with osteoblast cells. Int. J. Nanomedicine 2012, 7, 5593–5602.
  15. Boca S.C., Potara M., Gabudean A.M., Juhem A., Baldeck P.L., Astilean S.: Chitosan-coated triangular silver nanoparticles as a novel class of biocompatible, highly effective photothermal transducers for in vitro cancer cell therapy. Cancer Lett. 2011, 311, 131–140.
  16. Ma Z., Lim L.Y.: Uptake of Chitosan and Associated Insulin in Caco-2 Cell monolayers: A Comparison Between Chitosan Molecules and Chitosan Nanoparticles. Pharm. Res. 2003, 20, 1812–1819.
  17. Nam H.Y., Kwon S.M., Chung H., Lee S., Kwon S.H., Jeon H., Kim Y., Park J.H., Kim J., Her S., Oh Y.K., Kwon I.C., Kim K., Jeong S.Y.: Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles. J. Control. Release 2009, 135, 259–267.
  18. Chuah L.H., Roberts C.J., Billa N., Abdullah S., Rosli R.: Cellular uptake and anticancer effects of mucoadhesive curcumincontaining chitosan nanoparticles. Colloids Surf. B. 2014, 116, 228–236.
  19. Martins M.L., Saeki M.J., Telling M.T.F., Parra J.P.R., Landsgesell S., Smith R.I., Bordallo H.N.: Development and characterization of a new bio-nanocomposite (bio-NCP) for diagnosis and treatment of breast cancer. J. Alloy Comp. 2014, 584, 514–519.
  20. Vivek R., Nipun Babu V., Thangam R., Subramanian K.S., Kannana S.: pH-responsive drug delivery of chitosan nanoparticles as Tamoxifen carriers for effective anti-tumor activity in breast cancer cells. Colloids Surf. B. 2013, 111, 117–123.
  21. Vivek R., Thangam R., Nipun Babu V., Ponraj T., Kannan S.: Oxaliplatin-chitosan nanoparticles induced intrinsic apoptotic signaling pathway: A “smart” drug delivery system to breast cancer cell therapy. Int. J. Biol. Macromol. 2014, 65, 289–297.
  22. Kofuji K., Qian C., Nishimura M., Sugiyama I., Murata Y., Kawashima S.: Relationship between physicochemical characteristics and functional properties of chitosan. Eur. Polym. J. 2005, 41, 2784–2791.
  23. Zhang H., Neau S.H.: In vitro degradation of chitosan by bacterial enzymes from rat cecal and colonic contents. Biomaterials 2002, 23, 2761–2766.
  24. Henning T.: Polyethylene glycols (PEGs) and the pharmaceutical industry. Pharma Chem. 2002, 1, 57–59.
  25. Alcantar N.A., Aydil E.S., Israelachvili J.N.: Polyethylene glycol-coated biocompatible surfaces. Inc. J. Biomed. Mater. Res. 2000, 51, 343–351.
  26. Zhang Y., Kohler N., Zhang M.: Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials 2002, 23, 1553–1561.
  27. Parveen S., Sahoo S.K.: Long circulating chitosan/PEG blended PLGA nanoparticle for tumor drug delivery. Eur. J. Pharmacol. 2011, 670, 372–383.
  28. Park J.Y., Daksha P., Lee G.H., Woo S., Chang Y.: Highly water-dispersible PEG surface modified ultra small superparamagnetic iron oxide nanoparticles useful for target-specific biomedical applications. Nanotechnology 2008,19, 365–603.
  29. Mondini S., Drago C., Ferretti A.M., Puglisi A., Ponti A.: Colloidal stability of iron oxide nanocrystals coated with a PEGbased tetra-catechol surfactant. Nanotechnology 2013, 24, 105702.
  30. Lei P., Girshick S.L.: PEGylation of gold-decorated silica nanoparticles in the aerosol phase. Nanotechnology 2013, 24, 335602.
  31. Arima Y., Toda M., Iwata H.: Complement activation on surfaces modified with ethylene glycol units. Biomaterials 2008, 29, 551–560.
  32. Park K.: To PEGylate or not to PEGylate, that is not the question. J. Control. Release 2010, 142, 147–148.
  33. Narayanan D., Geena M.G., Lakshmi H., Koyakutty M., Nair S., Menon D.: Poly-(ethylene glycol) modified gelatin nanoparticles for sustained delivery of the anti-inflammatory drug Ibuprofen-Sodium: An in vitro and in vivo analysis, Nanomedicine 2013, 9, 818–828.
  34. Chen H., Paholak H., Ito M., Sansanaphongpricha K., Qian W., Che Y., Sun D.: Living PEGylation on gold nanoparticles to optimize cancer cell uptake by controlling targeting ligand and charge densities. Nanotechnology 2013, 24, 355101.
  35. Pozzi D., Colapicchioni V., Caracciolo G., Piovesana S., Capriotti A.L., Palchetti S., De Grossi S., Riccioli A., Amenitschf H., Lagana A.: Effect of polyethyleneglycol (PEG) chain length on the bio-nano-interactions between PEGylated lipid nanoparticles and biological fluids: from nanostructure to uptake in cancer cells. Nanoscale 2014, 6, 2782–2792.
  36. Lehner R., Wang X., Marsch S., Hunziker P.: Intelligent nanomaterials for medicine: Carrier platforms and targeting strategies in the context of clinical application. Nanomedicine 2013, 9, 742–757.
  37. Chao X., Guo L., Zhao Y., Hua K., Peng M., Chen C., Cui Y.: PEG-modified GoldMag nanoparticles (PGMNs) combined with the magnetic field for local drug delivery. J. Drug Target. 2011, 19, 161–170.
  38. Degliangeli F., Kshirsagar P., Brunetti V., Pompa P.P., Fiammengo R.: Absolute and Direct MicroRNA Quantification Using DNA-Gold Nanoparticle Probes. J. Am. Chem. Soc. 2014, 136, 2264–2267.
  39. Cao T., Yang Y., Sun Y., Wu Y., Gao Y., Feng W., Li F.: Biodistribution of sub-10 nm PEG-modified radioactive/upconversion nanoparticles. Biomaterials 2013, 34, 7127–7134.
  40. Iyer A.K., Khaled G., Fang J., Maeda H.: Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov. Today 2006, 11, 812– 818.
  41. Aggarwal S., Gupta S., Pabla D., Murthy R.S.R.: Gemcitabine-loaded PLGA-PEG immunonanoparticles for targeted chemotherapy of pancreatic cancer. Cancer Nano. 2013, 4, 145–157.
  42. Devanand Venkatasubbu G., Ramasamy S., Ramakrishnan V., Kumar J.: Folate targeted PEGylated titanium dioxide nanoparticles as a nanocarrier for targeted paclitaxel drug delivery. Adv. Powder Technol. 2013, 24, 947–954.
  43. Ding Y., Zhou Y.Y., Chen H., Geng D.D., Wu D.Y., Hong J., Shen W.B., Hang T.J., Zhang C.: The performance of thiolterminated PEG-paclitaxel-conjugated gold nanoparticles. Biomaterials 2013, 34, 10217–10227.
© Wroclaw Medical University