ceftriaxone sodyumun kontrollü salımı için çok katmanlı polimerik filmler

Abstract

Amaç: Bu çalışmanın amacı konakçı bölgede enfeksiyonu tedavi etmek amacıyla medikal alanda kullanılabilecek kontrollü salım sistemi hazırlamaktır.Yöntem: Mikro katmanlı filmler çözelti döküm metodu ile hazırlanmıştır. Üç katmanlı filmler kitosan CHI , jelatin GEL ve aljinat ALG kullanılarak aljinat tabakasına ceftriaxone sodyum CS yüklenmiş, ayrıca kontrol grubu için ilaç yüklenmemiş olarak hazırlanmış ve sırasıyla CHI /ALG/CHI ve CHI-GEL/ALG-CS/CHI-GEL olarak kodlandırılmıştır. Bütün filmler glutaraldehit GA buharına farklı süre boyunca 2 h, 10 h veya 24 h tabi tutularak çapraz bağlanmıştır. Filmlerin mekanik özellikleri ve CS’nin filmlerden salım kinetikleri üç farklı pH şartlarında pH 5,5, 7,4, ve 10,0 incelenmiştir. Salınan CS’nin Escherichia coli’ye karşı antibakteriyel etkinliği agar spot yöntemiyle test edilmiştir. Bulgular: Sonuçlar üç-katmanlı film yapılarının üst ve alt katmanında GEL varlığının filmlerin kırılganlığı önlediğini ve mekanik dayanımını arttırdığını, ancak orta katmanda CS varlığının mekanik özellikleri düşürdüğünü göstermiştir. Filmlerin GA ile çapraz bağlanması CS’nin salımında anlamlı bir etki göstermemiştir, ancak kitosanın aljinat ve CS ile etkileşiminden dolayı ilaç salım hızında azalma olmuştur. İlaç yüklü filmlerden salınan ilaç çözeltisinin kullanılmasıyla E. coli ile yapılan antibakteriyel deneyler, agar spor testlerinde inhibisyon zonu oluştuğunu göstermiştir. Sonuç: Çözücü döküm metodu ile hazırlanan çok katmanlı filmlerin medikal uygulamalarda ilaç taşıyıcı sistem olarak kullanım için iyi bir aday olduğu düşünülmektedir

Keywords

• Jelatin, kitosan, aljinat, ceftriaxone sodyum, polimerik film, ilaç salımı

Multilayer polymeric films for controlled release of ceftriaxone sodium

Abstract

Objective: The objective of this study was to prepare a controlled release system, which could be used in medical applications in order to treat infections at the host region.Methods: Microlayer films were prepared via solvent casting method. Films with 3-layers were prepared by using chitosan CHI , gelatin GEL and alginate ALG in the form of CHI /ALG/CHI and CHI-GEL /ALG/CHI-GEL with or without ceftriaxone sodium CS which is loaded in the middle ALG layer. All films were crosslinked by exposing them to glutaraldehyde GA vapor for different 2 h, 10 h or 24 h durations. Mechanical properties of the films and release kinetics of CS at three different pH conditions pH 5.5, 7.4, and 10.0 were investigated. The antibacterial efficiency of the released CS against Escherichia coli was examined via agar spot test.Results: The results indicated that the presence of GEL in the upper and lower layers of the 3-layer construct prevented fragility and increased the mechanical strength of the films, whereas the presence of CS in the middle layer caused decrease in the mechanical properties. Crosslinking with GA did not demonstrate a significant effect on the release profile of CS, but salım hızında azalma olmuştur. İlaç yüklü filmlerden salınan ilaç çözeltisinin kullanılmasıyla E. coli ile yapılan antibakteriyel deneyler, agar spor testlerinde inhibisyon zonu oluştuğunu göstermiştir. Sonuç: Çözücü döküm metodu ile hazırlanan çok katmanlı filmlerin medikal uygulamalarda ilaç taşıyıcı sistem olarak kullanım için iyi bir aday olduğu düşünülmektedir

Keywords

• Gelatin, chitosan, alginate, ceftriaxone sodium, polymeric film, drug release

References

1. 1. Song Z, Xu Y, Yang W, Cui L, Zhang J, Liu J. Graphene/ tri-block copolymer composites prepared via RAFT polymerizations for dual controlled drug delivery via pH stimulation and biodegradation. Eur Polym J, 2015; 69: 559-72.
2. 2. Mohanty S, Alm M, Hemmingsen M, DolatshahiPirouz A, Trifol J, Thomsen P, et al. 3D Printed Silicone–Hydrogel Scaffold with Enhanced Physicochemical Properties. Biomacromolecules, 2016, 17(4): 1321-9.
3. 3. Kim J, Hwang J, Seo Y, Jo Y, Son J, Paik T, et al. Engineered self-expander hydrogel for sustained release of drug molecules. J Ind Eng Chem, 2016, 42: 121-5.
4. 4. Dogan S, Demirer S, Kepenekci I, Erkek B, Kiziltay A, Hasirci N. et al. Epidermal growth factorcontaining wound closure enhances wound healing in non-diabetic and diabetic rats. Int Wound J, 2009, 6: 107-15.
5. 5. Ulubayram, K, Kiziltay A, Yilmaz E, Hasirci N. Desferrioxamine release from gelatin based sytems. Biotechnol Appl Bioc, 2005, 42: 237-45.
6. 6. Eke G, Mangir N, Hasirci N, MacNeil S, Hasirci V. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. Biomaterials, 2017, 129: 188-98.
7. 7. İmamoğlu Ö. Biyokontrolde Doğal Ürünlerin Kullanılması, Kitosan. Turk Hij Den Biyol Derg, 2011, 68(4): 215-22.
8. 8. Baghaie, S; Khorasani, M.T; Zarrabi, A; Moshtaghian, J. Wound healing properties of PVA/starch/chitosan hydrogel membranes with nano Zinc oxide as antibacterial wound dressing material. J Biomater Sci Polym Ed, 2017, 28: 2220-41.

9. 9. Dursun Usal T, Yucel D, Hasirci V. A novel GelMA-pHEMA hydrogel nerve guide for the treatment of peripheral nerve damages. Int J Biol Macromol, 2019, 121: 699-706.
10. 10. Reis RL, Neves NM, Mano JF, Gomes ME, Marques AP, Azevedo HS. Natural-Based Polymers for Biomedical Applications. Woodhead Publishing: Cambridge, England 2008.
11. 11. Tchobanian A, Oosterwyck HV, Fardim P. Polysaccharides for tissue engineering: Current landscape and future prospects. Carbohyd Polym, 2019, 205: 601-25.
12. 12. Ucar S, Ermis M, Hasirci N. Modified chitosan scaffolds: Proliferative, cytotoxic, apoptotic and necrotic effects on Saos-2 cells and antimicrobial effect on E.coli. J Bioact Compat Pol, 2016, 31: 304-19.
13. 13. Kara F, Aksoy EA, Calamak S, Hasirci N, Aksoy S. Immobilization of heparin on chitosan grafted polyurethane films to enhance its anti-adhesive and antibacterial properties against bacteria. J Bioact Compat Pol, 2016, 31: 72-90.
14. 14. Endogan T, Kiziltay A, Kose GT, Comunoglu N, Beyzadeoglu T, Hasirci N. Acrylic bone cements: Effects of the poly(methyl methacrylate) powder size and chitosan addition on their properties. J Appl Polym Sci, 2014,131: doi: 10.1002/app.39662.
15. 15. Balun Kayan D, Polat V. Improvement of electrochemical and structural properties of polycarbazole by simultaneous electrodeposition of chitosan. Turk J Chem, 2017, 41: 233-42.
16. 16. Isikli C, Hasirci V, Hasirci N. Development of Porous Chitosan-Gelatin/Hydroxyapatite Composite Scaffolds for Hard Tissue Engineering Applications. J Tissue Eng Regen Med, 2012, 6: 135-43.
17. 17. Sionkowska A, Kaczmarek B, Gadzala-Kopciuch R. Gentamicin release from chitosan and collagen composites. J Drug Deliv Sci Technol, 2016, 35: 353-359.
18. 18. Tønnesen HH, Karlsen J. Alginate in drug delivery systems. Drug Dev Ind Pharm, 2002, 28(6): 621-30
19. 19. Lee H, Woo HM, Kang BJ. Impact of collagenalginate composition from microbead morphological properties to microencapsulated canine adipose tissue-derived mesenchymal stem cell activities. J Biomater Sci Polym Ed, 2017, 6: 1-11.
20. 20. Finotelli PV, Da Silva D, Sola-Penna M, M Rossi A, Farina M, Andrade LR. Et al. Microcapsules of alginate/chitosan containing magnetic nanoparticles for controlled release of insulin. Colloids and Surfaces B, 2010, 81: 206-11.
21. 21. Tigli RS, Gumusderelioglu M. Evaluation of alginatechitosan semi IPNs as cartilage scaffolds. J Mater Sci Mater Med, 2009, 20: 699-709.
22. 22. Hritcu D, Popa MI, Popa N, Badescu V, Balan V. Preparation and characterization of magnetic chitosan nanospheres. Turk J Chem, 2009, 33: 785-96.
23. 23. Hammond PT. Building biomedical materials layerby-layer. Mater Today, 2012, 15: 196-206.
24. 24. Silva D, Pinto LFV, Bozukova D, Santos LF, Serro A P, Saramago B. Chitosan/alginate based multilayers to control drug release from ophthalmic lens. Colloids Surf B Biointerfaces, 2016, 147: 81-89.
25. 25. Zhang YZ, Venugopal J, Huang ZM, Lim C, Ramakrishna S. Crosslinking of the electrospun gelatin nanofibers. Polymer, 2006, 47: 2911-17.
26. 26. Isikli C, and Hasirci N. Surface and cell affinity properties of chitosan-gelatin-hydroxyapatite composite films. Key Eng Mater, 2012, 493-494: 337-342.
27. 27. Bouryabaf LS, Moradi M, Tajik H. Badali A. Biofilm Removal and Antimicrobial Activities of Agar Hydrogel Containing Salmonella typhimurium. J Med Bacteriol, 2017, 6: 51-58.
28. 28. Silva MA, Krause Bierhalz AC, Kieckbusch TG. Alginate and pectin composite films crosslinked with Ca2+ ions: Effect of the plasticizer concentration. Carbohydr Polym, 2009, 77: 736-42.
29. 29. Chou SF, Luo LJ, Lai JY, Kang Ma DH. Role of solventmediated carbodiimide cross-linking in fabrication of electrospun gelatin nanofibrous membranes as ophthalmic biomaterials. Mater Sci Eng C, 2017, 71: 1145-55.
30. 30. Bigi A, Cojazzi G, Panzavolta S, Rubinia K, Roveri N. Mechanical and thermal properties of gelatin films at different degrees of glutaraldehyde crosslinking. Biomaterials, 2001, 22: 763-68.
31. 31. Toncheva A, Mincheva R, Kancheva M, Manolova N, Rashkov I, Dubois P, Markova N. Antibacterial PLA/PEG electrospun fibers: Comparative study between grafting and blending PEG. Eur Polym J, 2016, 75: 223-33.
32. 32. Chou SF, Woodrow KA. Relationships between mechanical properties and drug release from electrospun fibers of PCL and PLGA blends. J Mech Behav Biomed Mater, 2017, 65: 724-33.
33. 33. M. Owens H, K. Dash A. Ceftriaxone Sodium: Comprehensive Profile. Profiles Drug Subst Excip Relat Methodol, 2003, 30: 21-57.
34. 34. Ofokansi KC, Adikwu MU, Okore VC. Preparation and Evaluation of Mucin-Gelatin Mucoadhesive Microspheres for Rectal Delivery of Ceftriaxone Sodium. Drug Dev Ind Pharm, 2007, 33: 691-700.
35. 35. Lalwani D. An oral dosage form of ceftriaxone sodium using enteric coated sustained release calcium alginate beads. MS, the Department of Pharmaceutical Sciences, The University of Toledo, 2015.
36. 36. Pasparakis G, Bouropoulos N. Swelling studies and in vitro release of verapamil from calcium alginate and calcium alginate–chitosan beads. Int J Pharm, 2006, 323: 34-42.