PMMA Nanokapsüllerin Çeşitli Formülasyon Değişkenlerinin Boyut, Morfoloji ve Zeta Potansiyel Üzerine Etkisinin İncelenmesi

Year 2024, , 407 - 415, 22.12.2024

Banu İyisan

https://doi.org/10.7240/jeps.1541464

Abstract

Bu çalışmanın amacı sağlık uygulamalarında geniş bir kullanım alanına sahip Polimetil Metakrilat (PMMA) nanokapsüllerin çeşitli formülasyon değişkenlerinin boyut, morfoloji ve zeta potansiyel üzerine etkisinin incelenmesi ve buradan elde edilen sonuçlarla formülasyon bileşenleri ile üretim sürecinin iyileştirilmesidir. Çalışmada, PMMA nanokapsüller miniemülsiyon çözücü buharlaştırma yöntemi kullanılarak başarı ile üretilmiş olup, elde edilen nanokapsüllerin karakterizasyonu ise dinamik ışık saçılımı yöntemi, elektroforetik ışık saçılımı yöntemi ve transmisyon elektron mikroskobu kullanılarak boyut, zeta potansiyel ve morfolojinin belirlenmesi şeklinde gerçekleştirilmiştir. Çalışma sürecinde PMMA miktarı artışı nanokapsül boyutunun artışına neden olmuş ve morfolojinin kapsülden küre formuna dönüşümü görülmüştür. Benzer şekilde sürfaktan miktarının artışı da morfoloji değişimine neden olmuş olup, sürfaktan miktarı azalışı ise boyutu önemli derecede artırmıştır. Çalışmanın bir diğer önemli bulgusu ise pirinç kepeği yağı içeren PMMA nanokapsül formülasyonun miniemülsiyon çözücü buharlaştırma yöntemi ile başarı ile üretildiği, ancak miniemülsiyon polimerizasyonunun bu noktada uygun bir üretim yöntemi olmadığıdır. Çalışmanın son adımında, optimum formülasyonu belirlenen PMMA nanokapsüllerinin yüzey özelliklerinin biyolojik perspektif ile iyileştirilmesine odaklanılmıştır. Bu amaçla yenilikçi ve pratik bir yaklaşımla yüzeyin polietilen glikol (PEG) bazlı sürfaktanlar ile kaplanması gerçekleştirilmiştir. Bunun ilerleyen çalışmalarda nanokapsüllerin kan akışında kalış süresini artırma potansiyeli olduğu düşünülmektedir. Çalışma sürecinde elde edilen üretim süreci ve formülasyonun iyileştirilmesine yönelik tüm bulgular, PMMA nanokapsüllerin sağlık uygulamalarında etkinliğinin artırılmasına katkı sağlayacaktır.

Keywords

polimer nanokapsüller, Nanopartikül Morfolojisi, Polimetil Metakrilat, Zeta Potansiyel, Nanokarakterizasyon

Thanks

Finansal destek için Max Planck Topluluğu tarafından desteklenen Max Planck Partner Grup Fonu aracılığıyla Max Planck Polimer Enstitüsü’ne ve destekleri için Prof. Dr. Katharina Landfester’e teşekkür ederim.

Investigating the Effects of Various Formulation Variables on the Size, Morphology and Zeta Potential of PMMA Nanocapsules

Abstract

The aim of the study is to investigate the effect of various formulation variables on the size, morphology, and zeta potential of PMMA nanocapsules, and to improve the formulation components and production process based on the results obtained. PMMA nanocapsules have been successfully produced using the miniemulsion solvent evaporation method and the characterization of the obtained nanocapsules was conducted by determining the size, zeta potential, and morphology using dynamic light scattering, electrophoretic light scattering methods, and transmission electron microscopy. During the study, an increase in the amount of PMMA led to an enlargement in nanocapsule size and the morphology changed from capsule to spherical form. Similarly, increasing surfactant amounts also changed the morphology, whereas a decrease in surfactant amount significantly increased the size. Another important finding was that PMMA nanocapsules containing rice bran oil could be successfully produced using the miniemulsion solvent evaporation method, yet miniemulsion polymerization was not found to be a suitable production method at this stage. In the final step of the study, the focus was to enhance the surface characteristics of the optimally formulated PMMA nanocapsules from a biological perspective. For this purpose, an innovative and practical approach was employed to coat the surface of the nanocapsules with PEG-bearing surfactants. This has the potential to increase the circulation time of the nanocapsules in the bloodstream in future studies. All findings related to the production process and formulation improvements obtained within the study will contribute to enhance the efficacy of PMMA nanocapsules in future biomedical applications.

Keywords

Polymer Nanocapsules, Nanoparticle Morphology, Polymethyl Methacrylate, Zeta Potential, Nanocharacterization

References

• Iyisan, B., Landfester, K. (2019). Polymeric nanocarriers. In Gehr, P., Zellner, R. (Eds.), Biological Responses to Nanoscale Particles. Nanoscience and Technology, Springer Nature Switzerland, (pp.53-84).
• Iyisan, B., Landfester, K. (2019). Modular approach for the design of smart polymeric nanocapsules. Macromolecular Rapid Communications, 40 (1), 1800577.
• Musyanovych, A., Landfester, K. (2014). Polymer micro- and nanocapsules as biological carriers with multifunctional properties. Macromolecular Bioscience, 14 (4), 458-477.
• Landfester, K., Mailänder, V. (2013). Nanocapsules with specific targeting and release properties using miniemulsion polymerization. Expert Opinion on Drug Delivery, 10(5), 593-609.
• Mitchell, M. J., Billingsley, M. M., Haley, R. M., Wechsler, M. E., Peppas, N. A., Langer, R. (2021). Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery, 20(2), 101-124.
• Poon, W., Kingston, B.R., Ouyang, B., Ngo, W., Chan, W.C.W. (2020). A framework for designing delivery systems. Nature Nanotechnology, 15, 819-829.
• Antonietti, M., Landfester, K. (2002). Polyreactions in miniemulsions. Progress in Polymer Science, 27, 689.
• Landfester, K. (2009). Miniemulsion polymerization and the structure of polymer and hybrid nanoparticles. Angewandte Chemie International Edition, 48, 4488.
• del Mercato, L. L., Ferraro, M. M., Baldassarre, F., Mancarella, S., Greco, V., Rinaldi, R., Leporatti, S. (2014). Biological applications of LbL multilayer capsules: from drug delivery to sensing. Advances in Colloid and Interface Science, 207, 139.
• Parakhonskiy, B.V., Yashchenok, A.M., Konrad, M., Skirtach, A.G. (2014). Colloidal micro- and nano-particles as templates for multilayer capsules. Advances in Colloid and Interface Science, 207, 253.
• Richardson, J., Chui, J., Björnmalm, M., Braunger, J. A., Ejima, H., Caruso, F. (2016). Innovation in layer-by-layer assembly. Chemical Reviews, 116, 14828.
• Gaitzsch, J., Huang, X., Voit, B. (2016). Engineering functional polymer capsules toward smart nanoreactors. Chemical Reviews, 116, 1053.
• Iyisan, B., Kluge, J., Formanek, P., Voit, B., Appelhans, D. (2016). Multifunctional and dual-responsive polymersomes as robust nanocontainers: design, formation by sequential post-conjugations, and pH-controlled drug release. Chemistry of Materials, 28(5), 1513-1525.
• Yassin, M. A., Appelhans, D., Wiedemuth, R., Formanek, P., Boye, S., Lederer, A., Voit, B. (2015). Overcoming concealment effects of targeting moieties in the PEG corona: controlled permeable polymersomes decorated with folate-antennae for selective targeting of tumor cells. Small, 11(13), 1580-1591.
• Iyisan, B., Thiramanas, R., Nazarova, N., Avlasevich, Y., Mailänder, V., Baluschev, S., Landfester, K. (2020). Temperature sensing in cells using polymeric upconversion nanocapsules. Biomacromolecules, 21, (11), 4469-4478.
• Bettencourt, A., Almeida, A. J. (2012). Poly(methyl methacrylate) particulate carriers in drug delivery. Journal of Microencapsulation, 29, 353−367.
• Kreuter, J. (2000). Poly(Methyl Methacrylate) nanoparticles as vaccine adjuvants. In: O’Hagan, D.T. (Eds.) Vaccine Adjuvants. Methods in Molecular Medicine™ (pp.105-119). Springer, Totowa, NJ.
• Zarrati, S., Mahdavi, M., Tabatabaie, F. (2016). Immune responses in DNA vaccine formulated with PMMA following immunization and after challenge with Leishmania majör. Journal of Parasit Diseases, 40, 427–435.
• Alves-Betista, F., Cunha Fontele, S.B., Beserra Santos, L.K., Alves-Filgueiras, L., Quaresma Nascimento, S., de Castro e Sousa, J.M., Ramos Gonçalves, J.C., Nogueira Mendes, A. (2020). Synthesis, characterization of α-terpineol loaded PMMA nanoparticles as proposed of therapy for melanoma. Materials Today Communications, 22, 100762.
• Sadguru Prasad, L.T., Madhusudhan, B., Kodihalli B, P. and Ghosh, P.C. (2017). Development and in vitro evaluation of oxytetracycline-loaded PMMA nanoparticles for oral delivery against anaplasmosis. IET Nanobiotechnology, 11, 119-126.
• Juneja, R., Roy, I. (2014). Surface modified PMMA nanoparticles with tunable drug release and cellular uptake, RSC Advances, 4, 44472.
• Paiphansiri, U., Tangboriboonrat, P., Landfester, K. (2006). Polymeric nanocapsules containing an antiseptic agent obtained by controlled nanoprecipitation onto water-in-oil miniemulsion droplets, Macromolecular Bioscience, 6, 33.
• Agmo Hernández, V. (2023). An overview of surface forces and the DLVO theory, ChemTexts, 9, 10.
• Tiarks, F., Landfester, K., Antonietti, M. (2001). Preparation of polymeric nanocapsules by miniemulsion polymerization. Langmuir, 17, 908-918.
• Roser, M., Fischer, D., Kissel, T. (1998). Surface-modified biodegradable albumin nano- and microspheres. II: effect of surface charges on in vitro phagocytosis and biodistribution in rats, European Journal of Pharmaceutics and Biopharmaceutics, 46 (3), 255-263.
• Ikeda-Imafuku, M., Li-Wen Wang, L., Rodrigues, D., Shaha, S., Zongmin, Z., Mitragotri, S. (2022). Strategies to improve the EPR effect: A mechanistic perspective and clinical translation, Journal of Controlled Release 345, 512–536.
• Owens, D.E., Peppas, N.A., (2006). Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles, International Journal of Pharmaceutics, 307, 93–102.
• Jiang, S., Mottola, M., Han, S., Thiramanas, R., Graf, R., Lieberwirth, I., Mailänder, V., Crespy, D., Landfester, K. (2020). Versatile preparation of silica nanocapsules for biomedical applications, Particle and particle systems characterization, 37, 1900484.