Pullulan-DOX/PVA-PDMS Biopolymeric Core-Shell Nanofibers Potential for Drug Delivery Systems

Yıl 2024, , 110 - 120, 30.09.2024

Elçin Tören , Adnan Ahmed Mazari

https://doi.org/10.7216/teksmuh.1496634

Öz

In this research, a novel drug delivery system shell was created by loading doxorubicin hydrochloride (DOX) into Pullulan and integrating the core into a polyvinyl alcohol (PVA) and Polydimethoxysilane (PDMS) composite matrix. The incorporation of DOX into the pullulan solution was carried out to take advantage of Pullulan's biocompatibility, biodegradability and hydrophilic nature. The hydrophilic nature of PVA can result in rapid drug release, while the hydrophobic nature of PDMS allows for slower drug release. The use of PVA-PDMS polymers together in the shell offers an initial rapid release followed by a prolonged and controlled drug release. This combination is superior to PVA or PDMS in terms of safety, mechanical strength, flexibility, controlled drug release and structural stability. This innovative composite system was designed to optimise DOX's controlled release to increase its therapeutic efficacy and reduce systemic toxicity. The kinetics of the drug release was characterised by an initial burst release followed by a sustained release phase, allowing controlled and prolonged release of the chemotherapeutic agent. Our results indicate that the pullulan/PVA-PDMS composite is a promising candidate for practical drug delivery applications, especially in cancer therapy.

Anahtar Kelimeler

Coaxial nanofibers, Polysaccharides, Antibacterial, Biomaterials, Bioactive nanofibers, Drug delivery systems

İlaç Dağıtım Sistemleri için Pullulan-DOX/PVA-PDMS Biyopolimerik Çekirdek-Kabuk Nanofiberler Potansiyeli

Öz

Bu araştırmada, doksorubisin hidroklorür (DOX) Pullulan'a yüklenerek ve çekirdek bir polivinil alkol (PVA) ve Polidimetoksisilan (PDMS) kompozit matrisine entegre edilerek yeni bir ilaç dağıtım sistemi kabuğu oluşturulmuştur. DOX'un pullulan çözeltisine dahil edilmesi, Pullulan'ın biyouyumluluğundan, biyolojik olarak parçalanabilirliğinden ve hidrofilik yapısından yararlanmak için gerçekleştirilmiştir. PVA'nın hidrofilik doğası hızlı ilaç salınımına neden olabilirken, PDMS'nin hidrofobik doğası daha yavaş ilaç salınımına izin verir. Kabukta PVA-PDMS polimerlerinin birlikte kullanılması, başlangıçta hızlı bir salım ve ardından uzun süreli ve kontrollü bir ilaç salımı sağlar. Bu kombinasyon güvenlik, mekanik güç, esneklik, kontrollü ilaç salınımı ve yapısal stabilite açısından PVA veya PDMS'den daha üstündür. Bu yenilikçi kompozit sistem, DOX'un terapötik etkinliğini artırmak ve sistemik toksisiteyi azaltmak için kontrollü salınımını optimize etmek üzere tasarlanmıştır. İlaç salınımının kinetiği, kemoterapötik ajanın kontrollü ve uzun süreli salınımına izin veren bir ilk patlama salınımı ve ardından sürekli bir salınım fazı ile karakterize edilmiştir. Sonuçlarımız pullulan/PVA-PDMS kompozitinin özellikle kanser tedavisinde pratik ilaç dağıtım uygulamaları için umut verici bir aday olduğunu göstermektedir.

Anahtar Kelimeler

Eş eksenli nanolifler, Polisakkaritler, Antibakteriyel, Biyo-malzemeler, Biyoaktif nanolifler, İlaç taşıma sistemleri

Kaynakça

• Barhoum A, Bechelany M, Hamdy Makhlouf AS. (2019). Handbook of Nanofibers. https://doi.org/10.1007/978-3-319-53655-2.
• Muthukrishnan L. (2022). An overview on electrospinning and its advancement toward hard and soft tissue engineering applications. Colloid Polym Sci; 300:875–901. https://doi.org/10.1007/s00396-022-04997-9.
• Elçin T. (2022). Pullulan/PVA/ Doxorubicin Core-Shell Electrospun Nanofibers Drug Delivery System For The Chemotherapy Against Cancer 2022:10. Conference Paper.
• Mauricio MD, Guerra-Ojeda S, Marchio P, Valles SL, Aldasoro M, Escribano-Lopez I, et al. (2018) Nanoparticles in Medicine: A Focus on Vascular Oxidative Stress. Oxidative Medicine and Cellular Longevity; 2018:e6231482. https://doi.org/10.1155/2018/6231482.
• Abid S, Hussain T, Raza ZA, Nazir A. (2019). Current applications of electrospun polymeric nanofibers in cancer therapy. Materials Science and Engineering: C; 97:966–77. https://doi.org/10.1016/j.msec.2018.12.105.
• Sahai N, Ahmad N, Gogoi M. (2018). Nanoparticles Based Drug Delivery for Tissue Regeneration Using Biodegradable Scaffolds: a Review. Curr Pathobiol Rep; 6:219–24. https://doi.org/10.1007/s40139-018-0184-8.
• Yang Y-Y, Wang Y, Powell R, Chan P. (2006). Polymeric Core-Shell Nanoparticles for Therapeutics. Clinical and Experimental Pharmacology and Physiology; 33:557–62. https://doi.org/10.1111/ j.1440-1681.2006.04408.x.
• Gopi S, Amalraj A, Sukumaran NP, Haponiuk JT, Thomas S. (2018). Biopolymers and Their Composites for Drug Delivery: A Brief Review. Macromolecular Symposia; 380:1800114. https://doi.org/10.1002/masy.201800114.
• Villarreal-Gómez LJ, Cornejo-Bravo JM, Vera-Graziano R, Grande D. (2016). Electrospinning as a powerful technique for biomedical applications: a critically selected survey. J Biomater Sci Polym Ed; 27:157–76. https://doi.org/10.1080/09205063.2015.1116885.
• Huang W-Y, Suye S, Fujita S. (2021). Cell Trapping via Migratory Inhibition within Density-Tuned Electrospun Nanofibers. ACS Appl Bio Mater; 4:7456–66. https://doi.org/10.1021/acsabm. 1c00700.
• Pérez-González GL, Villarreal-Gómez LJ, Serrano-Medina A, Torres-Martínez EJ, Cornejo-Bravo JM. (2019). Mucoadhesive electrospun nanofibers for drug delivery systems: applications of polymers and the parameters’ roles. Int J Nanomedicine; 14:5271–85. https://doi.org/10.2147/IJN.S193328.
• Torres E, Cornejo-Bravo J, Serrano-Medina A, perez gonzalez L, Villarreal-Gómez L. (2018). A Summary of Electrospun Nanofibers as Drug Delivery System: Drugs Loaded and Biopolymers Used as Matrices. Current Drug Delivery;15. https://doi.org/10.2174/1567201815666180723114326.
• Chavarria-Bolaños D, Granados-Hernandez M, Serrano J, Suárez Franco JL, Guarino V, Pérez M. (2018). Introduction to electrofluidodynamic techniques. PART II. cell-to-cell / material interactions.
• Li J, Liu Y, Abdelhakim H. (2022). Drug Delivery Applications of Coaxial Electrospun Nanofibres in Cancer Therapy. Molecules; 27:1803. https://doi.org/10.3390/molecules27061803.
• He C, Huang Z, Han X, Liu L, Zhang H, Chen L. (2006). Coaxial Electrospun Poly(L‐Lactic Acid) Ultrafine Fibers for Sustained Drug Delivery. Journal of Macromolecular Science, Part B; 45:515–24. https://doi.org/10.1080/00222340600769832.
• Reneker DH, Yarin AL, Fong H, Koombhongse S. (2000) Bending Instability of Electrically Charged Liquid Jets of Polymer Solutions in Electrospinning. Journal Of Applied Physics; 87:4531–47. https://doi.org/10.1063/1.373532.
• Sharma GK, James N. (2023). Electrospinning: The Technique and Applications. Recent Developments in Nanofibers Research, p. 118. https://doi.org/10.5772/intechopen.105804.
• Poláková L, Širc J, Hobzová R, Cocârță A-I, Heřmánková E. (2019). Electrospun nanofibers for local anticancer therapy: Review of in vivo activity. International Journal of Pharmaceutics; 558:268–83. https://doi.org/10.1016/j.ijpharm.2018.12.059.
• Hunley MT, Long TE. (2008). Electrospinning functional nanoscale fibers: A perspective for the future. Polymer International; 57:385–9.
• Baron PA, Deye GJ, Fernback J. (1994). Length Separation of Fibers. Aerosol Science and Technology; 21:179–92. https://doi.org/10.1080/02786829408959707.
• Gandhi UN, Goris S, Osswald TA, Song Y-Y. (2020). Discontinuous Fiber-Reinforced Composites Fundamentals and Applications.
• Fong Y, Chen C-H, Chen J-P. (2017). Intratumoral Delivery of Doxorubicin on Folate-Conjugated Graphene Oxide by In-Situ Forming Thermo-Sensitive Hydrogel for Breast Cancer Therapy. Nanomaterials; 7:388. https://doi.org/10.3390/nano7110388.
• Upadhyay S, Mantha AK, Dhiman M. (2020). Glycyrrhiza glabra (Licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes. J Ethnopharmacol; 258:112690. https://doi.org/10.1016/j.jep.2020.112690.
• Xiao D, Chang W, Ding W, Wang Y, Fa H, Wang J. (2020). Enhanced mitophagy mediated by the YAP/Parkin pathway protects against DOX-induced cardiotoxicity. Toxicol Lett; 330:96–107. https://doi.org/10.1016/j.toxlet.2020.05.015.
• Doxorubicin hydrochloride‐loaded electrospun poly(l‐lactide‐co‐ε‐caprolactone)/gelatin core–shell nanofibers for controlled drug release - Wang - 2021 - Polymer International - Wiley Online Library n.d. https://onlinelibrary.wiley.com/doi/10.1002/pi.6270 (accessed October 10, 2022).
• Yatmaz E, Turhan İ. (2012) Fermantasyon Yoluyla Pullulan Üretimi ve Gıda Endüstrisinde Kullanımı. Gıda 37,2, 95-102
• DeMerlis CC, Schoneker DR. (2003). Review of the oral toxicity of polyvinyl alcohol (PVA). Food Chem Toxicol; 41:319–26. https://doi.org/10.1016/s0278-6915(02)00258-2.
• Sia SK, Whitesides GM. (2003) Microfluidic devices fabricated in poly(dimethylsiloxane) for biological studies. Electrophoresis; 24:3563–76. https://doi.org/10.1002/elps.200305584.
• Yang D, Liu X, Jin Y, Zhu Y, Zeng D, Jiang X, et al. (2009). Electrospinning of poly(dimethylsiloxane)/poly(methyl methacrylate) nanofibrous membrane: fabrication and application in protein microarrays. Biomacromolecules; 10:3335–40. https://doi.org/10.1021/bm900955p.
• Bates NM, Puy C, Jurney PL, McCarty OJ, Hinds MT. (2020). Evaluation of the Effect of Crosslinking Method of Poly(Vinyl Alcohol) Hydrogels on Thrombogenicity. Cardiovasc Eng Technol; 11:448–55. https://doi.org/10.1007/s13239-020-00474-y.
• Sonker A, Verma V. (2017). Influence of crosslinking methods toward poly(vinyl alcohol) properties: Microwave irradiation and conventional heating. Journal of Applied Polymer Science 2017;135:46125. https://doi.org/10.1002/app.46125.
• Cai M-H, Chen X-Y, Fu L-Q, Du W-L, Yang X, Mou X-Z, et al. (2021). Design and Development of Hybrid Hydrogels for Biomedical Applications: Recent Trends in Anticancer Drug Delivery and Tissue Engineering. Front Bioeng Biotechnol; 9:630943. https://doi.org/10.3389/fbioe.2021.630943.
• Zarghami A, Irani M, Mostafazadeh A, Golpour M, Heydarinasab A, Haririan I. (2015). Fabrication of PEO/Chitosan/PCL/Olive Oil Nanofibrous Scaffolds for Wound Dressing Applications. Fibers and Polymers; 16:1201–12. https://doi.org/10.1007/s12221-015-1201-8.
• van der Weerd J, Kazarian SG. (2004). Combined approach of FTIR imaging and conventional dissolution tests applied to drug release. Journal of Controlled Release; 98:295–305. https://doi.org/10.1016/j.jconrel.2004.05.007.
• Cavallaro G, Lazzara G, Milioto S, Parisi F, Evtugyn V, Rozhina E, et al. (2018). Nanohydrogel Formation within the Halloysite Lumen for Triggered and Sustained Release. ACS Appl Mater Interfaces; 10:8265–73. https://doi.org/10.1021/acsami.7b19361.
• Philip L. Ritger NAP. (1987). A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. Journal of Controlled Release; 5:23–36.