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Aljinat, Karragenan, Jelatin ve Poli-(Laktik-ko-Glikolik Asit) Kompozit Mikroboncukları: Şişme, Sefaklor Yükleme ve Salınımı

Year 2025, Volume: 25 Issue: 4, 738 - 756, 04.08.2025
https://doi.org/10.35414/akufemubid.1560061

Abstract

Kompozit mikroboncuklar, aşağıdaki bileşenlerden ikisinin, üçünün veya dördünün bir kombinasyonu olarak sentezlendi: aljinat (A), karragenan (C), jelatin (G) ve/veya poli (laktik-ko-glikolik asit) (P). Burada, ilaç salınımında boncukların kullanılabilirliğini incelemek için model ilaç olarak Sefaklor (Cef) araştırıldı. İlaçlı ve ilaçsız kompozit mikroküreler farklı koşullar altında sentezlendi. Bu kompozitlerin Fourier Dönüşümlü Kızılötesi (FTIR) spektrumları karşılaştırıldı. Bileşen miktarları, çapraz bağlayıcı iyon miktarları gibi sentez koşullarının şişme, tutulma verimliliği ve malzemelerin salım kinetiği üzerindeki etkileri incelendi. Hidrojel kompozitlerinin maksimum şişme karşılaştırması A(981%)>AP(747%)>ACGP(641%)>ACG(618%)>ACP(464%)>AC(442%)>AGP(295%)>AG(157%) şeklindedir. Aljinat küresine PLGA eklenmesi şişme kontrastını azaltırken, diğer bileşenleri içeren kompozit boncuklara PLGA eklenmesi şişme %'sini artırır. ACP kürelerine eklenen PLGA miktarı arttıkça şişme azalır. Sefaklorun mikro kompozitlerdeki maksimum tutulma etkinliği ACP(93%)>AC(76%)>AP(66%)>ACG=AGP(46%)>AG(40%)>ACGP(39%)>A(36%)'dır. Tüm salım deneyleri, çalkalama ortamında yeni çözeltilerle, vücut sıcaklığında enzimsiz simüle edilmiş mide sıvısında gerçekleştirildi. Sefaklorun kompozit boncuklardan salımında genellikle bir patlama etkisi görülmedi. Seçilen veriler birinci dereceden salım kinetiğine ve Korsmeyer Peppas ve Higuchi ilaç salım modellerine uymaktadır.

References

  • Arsalan, A., Ahmad, I., Ali, S., A. 2017. in. Berthardt, L,V, (ed). Advances in Medicine and Biolog: Nova Science Publishers Inc., 123. pp 1-52. Bak, S., Lee, J.Y., Song, H., Hwang, J.H. and Lee, S.J. (2002). Controlled release and stabilization of Cefaclor from alginate-based matrices for oral delivery design. Journal of Pharmaceutical Investigation, 32, 327-330.
  • Baybaş, D., Serdaroğlu, G. and Semerci, B. 2021. The composite microbeads of alginate, carrageenan, gelatin, and poly (lactic-co-glycolic acid): Synthesis, characterization and Density Functional Theory calculations. International Journal of Biological Macromolecules, 181, 322-338. https://doi.org/10.1016/j.ijbiomac.2021.03.128
  • Brough, C., Miller, D.A., Keen, J.M., Kucera, S.A. and Lubda, D, 2016. Use of polyvinyl alcohol as a solubility-enhancing polymer for poorly water soluble drug delivery (Part 1). An Official Journal of the American Association of Pharmaceutical Scientists, 17(1), 167-179. https://doi.org/10.1208/s12249-015-0458y
  • Cavallaro, G., Fresta, M., Giammona, G., Puglisi, G. and Villari, A. 1994. Entrapment of β-lactams antibiotics in polyethylcyanoacrylate nanoparticles: Studies on the possible in vivo application of this colloidal delivery system. International Journal of Pharmaceutics, 111(1), 31-41. https://doi.org/10.1016/0378-5173(94)90399-9
  • Chilukala,S., Bontha, V.K., Pragada, R.R., 2016. In vitro and in vivo characterization of cefaclor loaded floating microspheres. Indo American Journal of Pharmaceutical Research 6(04), 5277. Chow, A.H., Ho, S.S., Tong, H.H. and Ma, H.H. 1998. Parameters affecting in-liquid drying microencapsulation and release rate of cefaclor. International journal of pharmaceutics, 172(1-2), 113-125. https://doi.org/10.1016/S0378-5173(98)00199-9
  • Chuang, J.J., Huang, Y.Y., Lo, S.H., Hsu, T.F., Huang, W.Y., Huang, S.L. and Lin, Y.S. 2017. Effects of pH on the shape of alginate particles and its release behavior. International Journal of Polymer Science, 2017(1), 3902704. https://doi.org/10.1155/2017/3902704
  • Dash, S., Murthy, P.N., Nath, L. and Chowdhury, P. 2010. Kinetic modeling on drug release from controlled drug delivery systems. Acta Poloniae Pharmaceutica, 67(3), 217-223. Davidovich-Pinhas, M. and Bianco-Peled, H. 2010. A quantitative analysis of alginate swelling. Carbohydrate Polymers, 79(4), 1020-1027. https://doi.org/10.1016/j.carbpol.2009.10.036
  • Faizan, M., Javed, M., Fatima, M., Bahadur, A., Iqbal, S., Mahmood, S. and Ibrahium, H.A. 2024. Incorporation of silane-modified halloysite into hydrogels for Cefaclor drug Release: Potential for wound healing application. Inorganic Chemistry Communications, 163, 112351. https://doi.org/10.1016/j.inoche.2024.112351
  • Jamroży, M., Kudłacik-Kramarczyk, S., Drabczyk, A., and Krzan, M., 2024. Advanced Drug Carriers: A Review of Selected Protein, Polysaccharide, and Lipid Drug Delivery Platforms. International Journal of Molecular Sciences, 25 (2), 786. https://doi.org/10.3390/ijms25020786
  • Karadağ, E., Ödemiş, H., Kundakçi, S. and Üzüm, Ö.B. 2016. Swelling characterization of acrylamide/zinc acrylate/xanthan gum/sepiolite hybrid hydrogels and Its application in sorption of janus green B from aqueous solutions. Advances in Polymer Technology, 35(3), 248-259. https://doi.org/10.1002/adv.21547
  • Kasai, R.D., Radhika, D., Archana, S., Shanavaz, H., Koutavarapu, R., Lee, D.Y. and Shim, J. 2023. A review on hydrogels classification and recent developments in biomedical applications. International Journal of Polymeric Materials and Polymeric Biomaterials, 72(13), 1059-1069. https://doi.org/10.1080/00914037.2022.2075872
  • Kolesnyk, I., Konovalova, V. and Burba, N.A. 2015. Alginate/κ-carrageenan microspheres and their applicatıon for protein drugs controlled release. Chemistry and Chemical Technology, 9(4), 485. Lin, C.C. and Metters, A.T. 2006. Hydrogels in controlled release formulations: network design and mathematical modeling. Advanced drug delivery reviews, 58(12-13), 1379-1408. https://doi.org/10.1016/j.addr.2006.09.004
  • Likhariya, M., Trivedi, D., Bhadoria, J., and Modi, A., 2021. Formulation and evaluation of cefaclor extended-release tablet. Journal of Drug Delivery and Therapeutics, 11(6-S), 33-36. https://doi.org/10.22270/jddt.v11i6-S.5193
  • Lio, D., Yeo, D. and Xu, C. 2016. Control of alginate core size in alginate-poly (Lactic-Co-Glycolic) acid microparticles. Nanoscale Research Letters, 11, 1-6. https://doi.org/10.1186/s11671-015-1222-7
  • Lorenz, L.J., Cefaclor. in: Florey, K. (ed.) 1980. Analytical profiles of drug substances, Academic Press, New York, vol. 9, 107–123. https://doi.org/10.1016/S0099-5428(08)60138-0
  • Mishra, M., (Ed.) 2015. Handbook of encapsulation and controlled release. CRC press. New York. Ofokansi, K.C,. Okorie, O. and Adikwu, M.U. 2009. Biodegradable microspheres based on gelatin–porcine mucin admixtures: In vitro and in vivo delivery studies. Biological and Pharmaceutical Bulletin, 32(10), 1754-1759. https://doi.org/10.1248/bpb.32.1754
  • Öztürk, A.A. and Aygül, A. 2020. Design of cefaclor monohydrate containing nanoparticles with extended antibacterial effect by nano-spray dryer: A nanoenglobing study. Journal of Research in Pharmacy, 24(1), 100-111. https://doi.org/10.35333/jrp.2020.115
  • Popa, E.G., Gomes, M.E. and Reis, R.L. 2011. Cell delivery systems using alginate–carrageenan hydrogel beads and fibers for regenerative medicine applications. Biomacromolecules, 12(11), 3952-3961. https://doi.org/10.1021/bm200965x
  • Rasool, B.K.A. and Fahmy, S. 2013. Development of coated beads for oral controlled delivery of cefaclor: In vitro evaluation. Acta Pharmaceutica, 63(1), 31-44. https://doi.org/10.2478/acph-2013-0003
  • Schott, H. 1992. Kinetics of swelling of polymers and their gels. Journal of Pharmaceutical Sciences, 81, 5, 467-470.
  • Semerci, B. 2019. Biyobozunur Polimer/Polisakkarit Kompozitleri İle Sefaklor Salımı, Yüksek Lisans Tezi, Sivas Cumhuriyet Üniversitesi Fen Bilimleri Enstitüsü, Sivas, 127.
  • Singh, S., Raut, S. Y., Kohli, K., & Kumar, S. 2022. Design and development of montmorillonite-sodium alginate microbeads for oral sustained delivery of cefaclor. Journal of Medical Pharmaceutical and Allied Science, 11 (3), 2634, 4986-4994. https://doi.org/10.55522/jmpas.V11I3.2634
  • Sun, S.B., Liu, P., Shao, F.M. and Miao, Q.L. 2015. Formulation and evaluation of PLGA nanoparticles loaded capecitabine for prostate cancer. International journal of clinical and experimental medicine, 8(10), 19670. Torres, L.G., Velasquez, A. and Brito-Arias, M.A. 2011. Ca-alginate spheres behavior in presence of some solvents and water-solvent mixtures. Advances in Bioscience and Biotechnology, 2, 8-12 https://doi.org/10.4236/abb.2011.210028-12
  • Xiao, C., Liu, H., Lu, Y. and Zhang, L.J, 2007. Blend films from sodium alginate and gelatin solutions. Journal of Macromolecular Science, Part A: Pure and Applied Chemistry A, 38(3), 317-328.

The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-co-Glycolic Acid): Swelling, Cefaclor Loading and Release

Year 2025, Volume: 25 Issue: 4, 738 - 756, 04.08.2025
https://doi.org/10.35414/akufemubid.1560061

Abstract

Composite microbeads were synthesized as a combination of two, three, or four of the following components: alginate(A), carrageenan(C), gelatin(G), and/or poly (lactic-co-glycolic acid)(P). Herein, Cefaclor(Cef) was investigated as a model drug to study the usability of the beads in drug delivery. The composite microspheres with medication and drug-free were synthesized under different conditions. Fourier Transform Infrared (FTIR) spectra of these composites were compared. The effects of synthesis conditions such as component amounts, cross-linker ion amounts on swelling, entrapment efficiency, and release kinetics of materials were examined. The maximum swelling comparison of the hydrogel composites is A(981%)>AP(747%)>ACGP(641%)>ACG(618%)>ACP(464%)>AC(442%)>AGP(295%)>AG(157%). Adding PLGA to the alginate sphere reduces the swelling contrast adding PLGA to the composite beads containing other components increases the swelling %. As the amount of PLGA added to the ACP spheres increases, the swelling decreases. The maximum entrapment efficiency of cefaclor in micro-composites is ACP(93%)>AC(76%)>AP(66%)>ACG=AGP(46%)>AG(40%)>ACGP(39%)>A(36%). All release experiments were carried out in simulated gastric fluid without enzyme at body temperature, with new solutions in a shaking medium. The release of cefaclor from the composite beads did not generally show a burst effect. The selected data fit the first-order release kinetics and the Korsmeyer Peppas and Higuchi drug release models.

References

  • Arsalan, A., Ahmad, I., Ali, S., A. 2017. in. Berthardt, L,V, (ed). Advances in Medicine and Biolog: Nova Science Publishers Inc., 123. pp 1-52. Bak, S., Lee, J.Y., Song, H., Hwang, J.H. and Lee, S.J. (2002). Controlled release and stabilization of Cefaclor from alginate-based matrices for oral delivery design. Journal of Pharmaceutical Investigation, 32, 327-330.
  • Baybaş, D., Serdaroğlu, G. and Semerci, B. 2021. The composite microbeads of alginate, carrageenan, gelatin, and poly (lactic-co-glycolic acid): Synthesis, characterization and Density Functional Theory calculations. International Journal of Biological Macromolecules, 181, 322-338. https://doi.org/10.1016/j.ijbiomac.2021.03.128
  • Brough, C., Miller, D.A., Keen, J.M., Kucera, S.A. and Lubda, D, 2016. Use of polyvinyl alcohol as a solubility-enhancing polymer for poorly water soluble drug delivery (Part 1). An Official Journal of the American Association of Pharmaceutical Scientists, 17(1), 167-179. https://doi.org/10.1208/s12249-015-0458y
  • Cavallaro, G., Fresta, M., Giammona, G., Puglisi, G. and Villari, A. 1994. Entrapment of β-lactams antibiotics in polyethylcyanoacrylate nanoparticles: Studies on the possible in vivo application of this colloidal delivery system. International Journal of Pharmaceutics, 111(1), 31-41. https://doi.org/10.1016/0378-5173(94)90399-9
  • Chilukala,S., Bontha, V.K., Pragada, R.R., 2016. In vitro and in vivo characterization of cefaclor loaded floating microspheres. Indo American Journal of Pharmaceutical Research 6(04), 5277. Chow, A.H., Ho, S.S., Tong, H.H. and Ma, H.H. 1998. Parameters affecting in-liquid drying microencapsulation and release rate of cefaclor. International journal of pharmaceutics, 172(1-2), 113-125. https://doi.org/10.1016/S0378-5173(98)00199-9
  • Chuang, J.J., Huang, Y.Y., Lo, S.H., Hsu, T.F., Huang, W.Y., Huang, S.L. and Lin, Y.S. 2017. Effects of pH on the shape of alginate particles and its release behavior. International Journal of Polymer Science, 2017(1), 3902704. https://doi.org/10.1155/2017/3902704
  • Dash, S., Murthy, P.N., Nath, L. and Chowdhury, P. 2010. Kinetic modeling on drug release from controlled drug delivery systems. Acta Poloniae Pharmaceutica, 67(3), 217-223. Davidovich-Pinhas, M. and Bianco-Peled, H. 2010. A quantitative analysis of alginate swelling. Carbohydrate Polymers, 79(4), 1020-1027. https://doi.org/10.1016/j.carbpol.2009.10.036
  • Faizan, M., Javed, M., Fatima, M., Bahadur, A., Iqbal, S., Mahmood, S. and Ibrahium, H.A. 2024. Incorporation of silane-modified halloysite into hydrogels for Cefaclor drug Release: Potential for wound healing application. Inorganic Chemistry Communications, 163, 112351. https://doi.org/10.1016/j.inoche.2024.112351
  • Jamroży, M., Kudłacik-Kramarczyk, S., Drabczyk, A., and Krzan, M., 2024. Advanced Drug Carriers: A Review of Selected Protein, Polysaccharide, and Lipid Drug Delivery Platforms. International Journal of Molecular Sciences, 25 (2), 786. https://doi.org/10.3390/ijms25020786
  • Karadağ, E., Ödemiş, H., Kundakçi, S. and Üzüm, Ö.B. 2016. Swelling characterization of acrylamide/zinc acrylate/xanthan gum/sepiolite hybrid hydrogels and Its application in sorption of janus green B from aqueous solutions. Advances in Polymer Technology, 35(3), 248-259. https://doi.org/10.1002/adv.21547
  • Kasai, R.D., Radhika, D., Archana, S., Shanavaz, H., Koutavarapu, R., Lee, D.Y. and Shim, J. 2023. A review on hydrogels classification and recent developments in biomedical applications. International Journal of Polymeric Materials and Polymeric Biomaterials, 72(13), 1059-1069. https://doi.org/10.1080/00914037.2022.2075872
  • Kolesnyk, I., Konovalova, V. and Burba, N.A. 2015. Alginate/κ-carrageenan microspheres and their applicatıon for protein drugs controlled release. Chemistry and Chemical Technology, 9(4), 485. Lin, C.C. and Metters, A.T. 2006. Hydrogels in controlled release formulations: network design and mathematical modeling. Advanced drug delivery reviews, 58(12-13), 1379-1408. https://doi.org/10.1016/j.addr.2006.09.004
  • Likhariya, M., Trivedi, D., Bhadoria, J., and Modi, A., 2021. Formulation and evaluation of cefaclor extended-release tablet. Journal of Drug Delivery and Therapeutics, 11(6-S), 33-36. https://doi.org/10.22270/jddt.v11i6-S.5193
  • Lio, D., Yeo, D. and Xu, C. 2016. Control of alginate core size in alginate-poly (Lactic-Co-Glycolic) acid microparticles. Nanoscale Research Letters, 11, 1-6. https://doi.org/10.1186/s11671-015-1222-7
  • Lorenz, L.J., Cefaclor. in: Florey, K. (ed.) 1980. Analytical profiles of drug substances, Academic Press, New York, vol. 9, 107–123. https://doi.org/10.1016/S0099-5428(08)60138-0
  • Mishra, M., (Ed.) 2015. Handbook of encapsulation and controlled release. CRC press. New York. Ofokansi, K.C,. Okorie, O. and Adikwu, M.U. 2009. Biodegradable microspheres based on gelatin–porcine mucin admixtures: In vitro and in vivo delivery studies. Biological and Pharmaceutical Bulletin, 32(10), 1754-1759. https://doi.org/10.1248/bpb.32.1754
  • Öztürk, A.A. and Aygül, A. 2020. Design of cefaclor monohydrate containing nanoparticles with extended antibacterial effect by nano-spray dryer: A nanoenglobing study. Journal of Research in Pharmacy, 24(1), 100-111. https://doi.org/10.35333/jrp.2020.115
  • Popa, E.G., Gomes, M.E. and Reis, R.L. 2011. Cell delivery systems using alginate–carrageenan hydrogel beads and fibers for regenerative medicine applications. Biomacromolecules, 12(11), 3952-3961. https://doi.org/10.1021/bm200965x
  • Rasool, B.K.A. and Fahmy, S. 2013. Development of coated beads for oral controlled delivery of cefaclor: In vitro evaluation. Acta Pharmaceutica, 63(1), 31-44. https://doi.org/10.2478/acph-2013-0003
  • Schott, H. 1992. Kinetics of swelling of polymers and their gels. Journal of Pharmaceutical Sciences, 81, 5, 467-470.
  • Semerci, B. 2019. Biyobozunur Polimer/Polisakkarit Kompozitleri İle Sefaklor Salımı, Yüksek Lisans Tezi, Sivas Cumhuriyet Üniversitesi Fen Bilimleri Enstitüsü, Sivas, 127.
  • Singh, S., Raut, S. Y., Kohli, K., & Kumar, S. 2022. Design and development of montmorillonite-sodium alginate microbeads for oral sustained delivery of cefaclor. Journal of Medical Pharmaceutical and Allied Science, 11 (3), 2634, 4986-4994. https://doi.org/10.55522/jmpas.V11I3.2634
  • Sun, S.B., Liu, P., Shao, F.M. and Miao, Q.L. 2015. Formulation and evaluation of PLGA nanoparticles loaded capecitabine for prostate cancer. International journal of clinical and experimental medicine, 8(10), 19670. Torres, L.G., Velasquez, A. and Brito-Arias, M.A. 2011. Ca-alginate spheres behavior in presence of some solvents and water-solvent mixtures. Advances in Bioscience and Biotechnology, 2, 8-12 https://doi.org/10.4236/abb.2011.210028-12
  • Xiao, C., Liu, H., Lu, Y. and Zhang, L.J, 2007. Blend films from sodium alginate and gelatin solutions. Journal of Macromolecular Science, Part A: Pure and Applied Chemistry A, 38(3), 317-328.
There are 24 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other), Biomaterial , Polymer Science and Technologies
Journal Section Articles
Authors

Buse Semerci Arıkan 0000-0002-7899-1073

Demet Baybaş 0000-0002-7712-754X

Early Pub Date July 21, 2025
Publication Date August 4, 2025
Submission Date October 4, 2024
Acceptance Date February 3, 2025
Published in Issue Year 2025 Volume: 25 Issue: 4

Cite

APA Semerci Arıkan, B., & Baybaş, D. (2025). The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-co-Glycolic Acid): Swelling, Cefaclor Loading and Release. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 25(4), 738-756. https://doi.org/10.35414/akufemubid.1560061
AMA Semerci Arıkan B, Baybaş D. The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-co-Glycolic Acid): Swelling, Cefaclor Loading and Release. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. August 2025;25(4):738-756. doi:10.35414/akufemubid.1560061
Chicago Semerci Arıkan, Buse, and Demet Baybaş. “The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-Co-Glycolic Acid): Swelling, Cefaclor Loading and Release”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 25, no. 4 (August 2025): 738-56. https://doi.org/10.35414/akufemubid.1560061.
EndNote Semerci Arıkan B, Baybaş D (August 1, 2025) The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-co-Glycolic Acid): Swelling, Cefaclor Loading and Release. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 25 4 738–756.
IEEE B. Semerci Arıkan and D. Baybaş, “The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-co-Glycolic Acid): Swelling, Cefaclor Loading and Release”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 25, no. 4, pp. 738–756, 2025, doi: 10.35414/akufemubid.1560061.
ISNAD Semerci Arıkan, Buse - Baybaş, Demet. “The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-Co-Glycolic Acid): Swelling, Cefaclor Loading and Release”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 25/4 (August2025), 738-756. https://doi.org/10.35414/akufemubid.1560061.
JAMA Semerci Arıkan B, Baybaş D. The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-co-Glycolic Acid): Swelling, Cefaclor Loading and Release. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2025;25:738–756.
MLA Semerci Arıkan, Buse and Demet Baybaş. “The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-Co-Glycolic Acid): Swelling, Cefaclor Loading and Release”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 25, no. 4, 2025, pp. 738-56, doi:10.35414/akufemubid.1560061.
Vancouver Semerci Arıkan B, Baybaş D. The Composite Microbeads of Alginate, Carrageenan, Gelatin, and Poly-(Lactic-co-Glycolic Acid): Swelling, Cefaclor Loading and Release. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2025;25(4):738-56.