مروری کوتاه بر کیتوسان و میکروذرات آن به عنوان حامل در سامانه ‏های دارورسانی

نوع مقاله: تالیفی

نویسندگان

1 دانشگاه تربیت مدرس

2 استادیار دانشکده مهندسی شیمی، گروه زیست پزشکی، دانشگاه تربیت مدرس

3 استادیار گروه سامانه های نوین دارورسانی، پژوهشگاه پلیمر و پتروشیمی ایران

چکیده

تهیه، تولید و توسعه هر مولکول دارویی بسیار پرهزینه و زمان‌بر است. ازاین‌رو، تلاش‌هایی به‌منظور افزایش ایمنی و اثربخشی داروهای رایج، با روش‌هایی مانند دارودرمانی شخص‌محور، تعیین غلظت و ردیابی داروها افزایش یافته است. از روش‌های بسیار کارآمد در این زمینه، انتقال هدفمند و کنترل سرعت رهایش داروهاست. علم دارورسانی به‌دنبال افزایش زیست‌ دسترس‌پذیری، کاهش عوارض جانبی، انتقال هدفمند داروها به محل‌های مدنظر و نیز گذر از سدِ برخی موانع، مانند موانع خونی-مغزی، است. در تهیه هر سامانه دارورسانی، انتخاب پلیمر از بخش‌های بسیار مهم و حیاتی به‌شمار می‌رود. طی سه دهه اخیر کاربردهای زیست‌پزشکی گسترده برای ترکیب کیتوسان از خانواده کیتین، گزارش شده است. در این مقاله، ویژگی‌های طبیعی‌بودن این پلیمر، به‌عنوان عامل اصلی کاربرد گسترده آن در زمینه‌های مختلف زیست‌پزشکی و روش‌های تهیه میکروذرات کیتوسان، بر پایه کاربردهای آن در دارورسانی نوین، بررسی می‌شود.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Chitosan and Its Microparticles as Carriers in Drug Delivery Systems: An Overview

نویسنده [English]

  • Mohsen Sadeghi 1
چکیده [English]

The development of a new drug molecule is an expensive and time consuming effort. Improving the safety efficacy ratio of old drugs has been attempted by different methods focused on each individual drug therapy, dose specification and therapeutic drug monitoring. Controlled rate delivery, slow delivery and targeted delivery are other very promising methods which have been pursued intensively. Methods for increasing bioavailability, diminishing side-effects, promoting targeted delivery and treating conditions such as blood-brain barrier disorders, are the main topics in novel drug delivery explorations. Choosing a suitable polymer is one of the most important aspects in development of a drug delivery system. In the last three decades, avast number of biomedical applications have been reported for a chitin derivative, known as chitosan. In this overview the properties of this polymer, as a natural compound, which are the main criteria for its extensive application in different areas of biomedicine are described, specifically in relation to synthesis of chitosan microparticles applied in novel drug delivery.

کلیدواژه‌ها [English]

  • chitosan properties
  • chitosan microparticles
  • drug delivery
  • spray drying
  • ionic gelation
1. Reddy P.D. and Swarnalatha D., Recent Advances in Novel Drug Delivery Systems, Int. J. Pharm. Tech. Res., 2, 2025-
2027, 2010.
2. Mainardes R.M. and Silva L.P., Drug Delivery Systems: Past, Present, and Future, Curr. Drug Targets., 5, 449-455, 2004.
3. Sinha V.R., Singla A.K., Wadhawan S., Kaushik R., Kumria R., Bansal K., and Dhawan S., Chitosan Microspheres as a
Potential Carrier for Drugs, Int. J. Pharm., 274, 1-33, 2004.
4. Nikander K., Drug Delivery Systems, J. Aerosol. Med., 7, 19- 24, 1994.

5. Anitha A., Sowmya S., Kumar P.T.S., Deepthi S., Chennazhi K.P., Ehrlich H., Tsurkan M., and Jayakumar R., Chitin and Chitosan in Selected Biomedical Applications, Prog. Polym. Sci., 39, 1644-1667, 2014.

6. Rinaudo M., Chitin and Chitosan: Properties and Applications, Prog. Polym. Sci., 31, 603-632, 2006.
7. Pillai C.K.S., Paul W., and Sharma C.P., Chitin and Chitosan Polymers: Chemistry, Solubility and Fiber Formation, Prog.
Polym. Sci., 34, 641-678, 2009.
8. Ravi Kumar M.N.V., A Review of Chitin and Chitosan Applications, React. Funct. Polym., 46, 1-27, 2000.
9. Raymond L., Morin F.G., and Marchessault R.H., Degree of Deacetylation of Chitosan Using Conductometric Titration
and Solid-State NMR, Carbohydr. Res., 246, 331-336, 1993.
10. Zając A., Hanuza J., Wandas M., and Dymińska L., Determination of N-acetylation Degree in Chitosan Using Raman
Spectroscopy, Spectrochim. Acta, Part A, 134, 114-120, 2015.
11. Bagheri-Khoulenjani S., Taghizadeh S.M., and Mirzadeh H., An Investigation on The Short-Term Biodegradability of Chitosan with Various Molecular Weights and Degrees of Deacetylation, Carbohydr. Polym., 78, 773-778, 2009.
12. Taghizadeh S.M., Takroosta M., Davoodi G., and Yousefi M., Preparation of Chitosan with Different Degree of Deacetylation and Comparison of Its Different Characterization Methods, Iran. J. Polym. Sci. Technol. (Persian), 17, 291-297, 2004.
13. Wu A.C., Bough W.A., Conrad E.C., and Alden K.E. (Jr.), Determination of Molecular-Weight Distribution of Chitosan by
High-Performance Liquid Chromatography, J. Chromatogr., 128, 87-99, 1976.
14. Taghizadeh S.M. and Davari G., Preparation, Characterization, and Swelling Behavior of N-Acetylated and Deacetylated
Chitosans, Carbohydr. Polym., 64, 9-15, 2006.
15. Kumar M.N. and Kumar N., Polymeric Controlled Drug-Delivery Systems: Perspective Issues and Opportunities, Drug.
Dev. Ind. Pharm., 27, 1-30, 2001.
16. Tokura S., Nishi N., and Noguchi J., Studies on Chitin. III. Preparation of Chitin Fibers, Polym. J., 11, 781-786, 1979.
17. Rinaudo M., Pavlov G., and Desbrières J., Influence of Acetic Acid Concentration on the Solubilization of Chitosan, Polymer, 40, 7029-7032, 1999.
18. Rinaudo M., Pavlov G. and Desbrières J., Solubilization of Chitosan in Strong Acid Medium, Int. J. Polym. Anal. Charact., 5, 267-276, 1999.
19. Cho J., Heuzey M.C., Bégin A., and Carreau P.J., Physical Gelation of Chitosan in the Presence of β-Glycerophosphate:
The Effect of Temperature, Biomacromolecules, 6, 3267- 3275, 2005.
20. Zoldners J., Kiseleva T., and Kaiminsh I., Influence of Ascorbic Acid on The Stability of Chitosan Solutions, Carbohydr.
Polym., 60, 215-218, 2005.
21. Hsu S.C., Don T.M., and Chiu W.Y., Free Radical Degradation of Chitosan with Potassium Persulfate, Polym. Degrad.
Stabil., 75, 73-83, 2002.
22. Yang Y.M., Hu W., Wang X.D., and Gu X.S., The Controlling Biodegradation of Chitosan Fibers by N-Acetylation In Vitro
and In Vivo, J. Mater. Sci. Mater. M., 18, 2117-2121, 2007.
23. Taghizadeh S.M. and Javan R.S., Dynamic Parameters in Preparing Chitosan Nanoparticles with Incorporation Method Using Novel Drug Delivery Systems, Iran. J. Polym. Sci. Technol (Persian), 23, 103-110, 2010.
24. Sadeghi M., Ganji F., and Taghizadeh S.M., Preparation and Optimization of Labeled Chitosan Nanoparticles and Evaluation of Their Release from Transdermal Drug Delivery System,
Iran. J. Polym. Sci. Technol. (Persian), 28, 333-344, 2015.
25. Sadeghi M., Ganji F., Taghizadeh S.M., and Daraei B., Preparation and Characterization of Rivastigmine Transdermal
Patch Based on Chitosan Microparticles, Iran. J. Pharm. Res., 15, 283-294, 2016.
26. Khodaverdi E., Ganji F., Tafaghodi M., and Sadoogh M., Effects of Formulation Properties on Sol-Gel Behavior of Chitosan/ Glycerolphosphate Hydrogel, Iran. Polym. J., 22, 785- 790, 2013.
27. Ganji F. and Abdekhodaie M.J., The Effects of Reaction Conditions on Block Copolymerization of Chitosan and
Poly(Ethylene Glycol), Carbohydr. Polym., 81, 799-804, 2010.
28. Ganji F. and Abdekhodaie M.J., Synthesis and Characterization of a New Thermosensitive Chitosan–PEG Diblock Copolymer, Carbohydr. Polym., 74, 435-441, 2008.
29. Ghasemi Tahrir F., Ganji F., Mani A.R., and Khodaverdi E., In Vitro and In Vivo Evaluation of Thermosensitive Chitosan
Hydrogel for Sustained Release of Insulin, Drug Deliv., 23, 1038-1046, 2016.
30. Jayakumar R., Menon D., Manzoor K., Nair S.V., and Tamura H., Biomedical Applications of Chitin and Chitosan Based

Nanomaterials-A Short Review, Carbohydr. Polym., 82, 227- 232, 2010.
31. Grenha A., Chitosan Nanoparticles: A Survey of Preparation Methods, J. Drug. Target., 20, 291-300, 2012.
32. Nair R., Reddy B.H., Kumar A., Kumar C.K., and Jayraj K., Application of Chitosan Microspheres as Drug Carriers: A Review, Pharm. Sci. Res., 1, 1-12, 2009.
33. Yun Y.H., Lee B.K., and Park K., Controlled Drug Delivery: Historical Perspective for The Next Generation, J. Control.
Release., 2015, doi: 10.1016/j.jconrel.2015.10.005.
34. Mitra A. and Dey B., Chitosan Microspheres in Novel Drug Delivery Systems, Indian. J. Pharm. Sci., 73, 355-366, 2011.
35. Denkbas E.B., Odabasi M., Kiliçay E., and Özdemir N., Human Serum Albumin (HSA) Adsorption with Chitosan Microspheres, J. Appl. Polym. Sci., 86, 3035-3039, 2002.
36. Sun Y., Liu Y., Liu W., Lu C., and Wang L., Chitosan Microparticles Ionically Cross-Linked with Poly(Γ-Glutamic
Acid) as Antimicrobial Peptides and Nitric Oxide Delivery Systems, Biochem. Eng. J., 95, 78-85, 2015.
37. Coppi G. and Iannuccelli V., Alginate/Chitosan Microparticles for Tamoxifen Delivery to the Lymphatic System, Int. J.
Pharm., 367, 127-132, 2009.
38. Guliyeva U., Oner F., Ozsoy S., and Haziroglu R., Chitosan Microparticles Containing Plasmid DNA as Potential Oral
Gene Delivery System, Eur. J. Pharm. Biopharm., 62, 17-25, 2006.
39. He P., Davis S.S., and Illum L., Chitosan Microspheres Prepared by Spray Drying, Int. J. Pharm., 187, 53-65, 1999.
40. Filipovic-Grcic J., Perissutti B., Moneghini M., Voinovich D., Martinac A., and Jalsenjak I., Spray-Dried Carbamazepine-
Loaded Chitosan and HPMC Microspheres: Preparation and Characterisation, J. Pharm. Pharmacol., 55, 921-931, 2003.
41. Takahashi H., Chen R., OkamotoH., and Danjo K., Acetaminophen Particle Design Using Chitosan and a Spray-Drying
Technique, Chem. Pharm. Bull. (Tokyo), 53, 37-41, 2005.
42. Alhalaweh A., Andersson S., and Velaga S.P., Preparation of Zolmitriptan-Chitosan Microparticles by Spray Drying for
Nasal Delivery, Eur. J. Pharm. Sci., 38, 206-214, 2009.
43. Lim S.T., Martin G.P., Berry D.J., and Brown M.B., Preparation and Evaluation of The In Vitro Drug Release Properties
and Mucoadhesion of Novel Microspheres of Hyaluronic Acid and Chitosan, J. Control. Release, 66, 281-292, 2000.
44. Bogataj M., Mrhar A., Grabnar I., Rajtman Z., Bukovec P., Srcic S., and Urleb U., The Influence of Magnesium Stearate
on The Characteristics of Mucoadhesive Microspheres, J. Microencapsul., 17, 499-508, 2000.
45. Kriznar B., Mateovic T., Bogataj M., and Mrhar A., The Influence of Chitosan on In Vitro Properties of Eudragit RS Microspheres, Chem. Pharm. Bull. (Tokyo), 51, 359-364, 2003.
46. Orienti I., Aiedeh K., Gianasi E., Bertasi V., and Zecchi V., Indomethacin Loaded Chitosan Microspheres. Correlation
Between The Erosion Process and Release Kinetics, J. Microencapsul., 13, 463-472, 1996.
47. Gonzalez-Rodriguez M.L., Holgado M.A., Sanchez-Lafuente C., Rabasco A.M., and Fini A., Alginate/Chitosan Particulate
Systems for Sodium Diclofenac Release, Int. J. Pharm., 232, 225-234, 2002.
48. Rao N.R., Kulkarni U., Deshmukh A., and Suresh D., Preparation and Characterization of Ionotropic Cross-Linked Chitosan Microparticles for Controlled Release of Aceclofenac, Int. J. Pharm. Sci. Drug. Res., 2, 107-111, 2010.
49. Wassmer S., Rafat M., Fong W.G., Baker A.N., and Tsilfidis C., Chitosan Microparticles for Delivery of Proteins to The
Retina, Acta Biomater., 9, 7855-7864, 2013.
50. Wilson B., Brain Targeting PBCA Nanoparticles and The Blood-Brain Barrier, Nanomedicine (Lond), 4, 499-502, 2009.
51. Martins A.F., de Oliveira D.M., Pereira A.G., Rubira A.F., and Muniz E.C., Chitosan/TPP Microparticles Obtained by Microemulsion Method Applied in Controlled Release of Heparin, Int. J. Biol. Macromol., 5, 1127-1133, 2012.
52. Pichayakorn W. and Boonme P., Evaluation of Cross-Linked Chitosan Microparticles Containing Metronidazole for Periodontitis Treatment, Mater. Sci. Eng. C: Mater., 33, 1197- 1202, 2013.
53. Pavanetto F., Perugini P., Conti B., Modena T., and Genta I., Evaluation of Process Parameters Involved in Chitosan
Microsphere Preparation by The O/W/O Multiple Emulsion Method, J. Microencapsul., 13, 679-688, 1996.
54. Kumbar S.G., Kulkarni A.R., and Aminabhavi M., Crosslinked Chitosan Microspheres for Encapsulation of Diclofenac
Sodium: Effect of Crosslinking Agent, J. Microencapsul., 19, 173-180, 2002.
55. Kumbar S.G., Soppimath K.S., and Aminabhavi T.M., Synthesis and Characterization of Polyacrylamide-Grafted Chitosan Hydrogel Microspheres for The Controlled Release of Indo methacin, J. Appl. Polym. Sci., 87, 1525-1536, 2003.

56. Berthold A., Cremer K., and Kreuter J., Preparation and Characterization of Chitosan Microspheres as Drug Carrier for
Prednisolone Sodium Phosphate as Model for Anti-Inflammatory Drugs, J. Control. Release, 39, 17-25, 1996.
57. Vasconcellos F.C., Goulart G.A.S., and Beppu M.M., Production and Characterization of Chitosan Microparticles Containing Papain for Controlled Release Applications, Powder. Technol., 205, 65-70, 2011.
58. Dhanasingh S. and Nallaperumal S.K., Chitosan/Casein Microparticles: Preparation, Characterization and Drug Release
Studies, Int. J. Res. Eng. Appl. Sci., 6, 234-238, 2010.
59. Butstraen C. and Salaün F., Preparation of Microcapsules by Complex Coacervation of Gum Arabic and Chitosan, Carbohydr. Polym., 99, 608-616, 2014.
60. Lacerda L., Parize A.L., Fávere V., Laranjeira M.C.M., and Stulzer H.K., Development and Evaluation of Ph-Sensitive
Sodium Alginate/Chitosan Microparticles Containing The Antituberculosis Drug Rifampicin, Mater. Sci. Eng. C: Mater.,
39, 161-167, 2014.
61. Estevinho B.N., Rocha F., Santos L., and Alves A., Microencapsulation with Chitosan by Spray Drying for Industry Applications – A Review, Trends Food Sci. Tech., 31, 138-155, 2013.
62. Maquet V. and Gautier S., Preparation of Chitosan Microparticles by Spray Drying, http://www.sigmaaldrich.com/
materials-science/polymer-science/chitosan.html, Available in 10/19/2016.
63. Agnihotri S.A., Mallikarjuna N.N., and Aminabhavi T.M., Recent Advances on Chitosan-Based Micro- and Nanoparticles
in Drug Delivery, J. Control. Release., 100, 5-28, 2004.
64. Taranejoo S., Janmaleki M., Rafienia M., Kamali M., and Mansouri M., Chitosan Microparticles Loaded with Exotoxin
A Subunit Antigen for Intranasal Vaccination Against Pseudomonas Aeruginosa: An In Vitro Study, Carbohydr. Polym., 83,
1854-1861, 2011.
65. Mesquita P.C., Oliveira A.R., Pedrosa M.F.F., de Oliveira A.G., and da Silva-Júnior A.A., Physicochemical Aspects Involved in Methotrexate Release Kinetics from Biodegradable Spray-Dried Chitosan Microparticles, J. Phys. Chem. Solids,
81, 27-33, 2015.
66. Cerchiara T., Abruzzo A., Parolin C., Vitali B., Bigucci F., Gallucci M.C., Nicoletta F.P., and Luppi B., Microparticles
Based on Chitosan/Carboxymethylcellulose Polyelectrolyte Complexes for Colon Delivery of Vancomycin, Carbohydr.
Polym., 143, 124-130, 2016.
67. Li Y.P., Machida T.Y., Sannan T., and Nagai T., Preparation of Chitosan Microspheres Containing Fluorouracil Using The
‘Dry-In-Oil’ Method and Its Release Characteristics, STP. Pharma. Sci., 1, 363-368, 1991.
68. Suresh P., Kurrey A., and Singh M., Hollow Microspheres as a Drug Carrier: An Overview of Fabrication Andin Vivocharacterization Techniques, Chron. Young Sci., 5, 1-10, 2014.
69. Liu C., Tan Y., Liu C., Chen X.,  and Yu L., Preparations, Characterizations and Applications of Chitosan-Based Nanoparticles, J. Ocean Univ. China, 6, 237-243, 2007.
70. Chavez de Paz L.E., Resin A., Howard K.A., Sutherland D.S., and Wejse P.L., Antimicrobial Effect of Chitosan Nanoparticles on Streptococcus Mutans Biofilms, Appl. Environ. Microbiol., 77, 3892-3895, 2011.
71. Wassmer S., Rafat M., Fong W.G., Baker A.N., and Tsilfidis C., Chitosan Microparticles for Delivery of Proteins to The
Retina, Acta Biomater., 9, 7855-7864, 2013.
72. Kumar S.S., Saha A.k., Kavitha K., and Basu S.K., Preparation and Characterization of Indomethacin Loaded Ionically
Cross-Linked Microspheres Using Chitosan, Der Pharmacia Lettre (Scholar Research Library), 4, 33-41, 2012.