Araştırma Makalesi
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Evaluation of Waste Snake Molt as a Delivery System and in Vitro Release of D-Panthenol

Yıl 2023, , 99 - 106, 30.12.2023
https://doi.org/10.29002/asujse.1298383

Öz

Biomolecules such as collagen, silk and keratin are frequently preferred in medical fields as wound healing and drug delivery systems, thanks to their many unique properties. Keratin-based materials, which are a strong structural proteins such as feathers, hooves, hair and wool, are preferred for drug release because they are nanotoxic and biocompatible. However, no studies have been conducted on the drug release of the snake skin containing keratin as a structural protein. Controlled drug release is very important in terms of maximum benefit, minimum harm and patient comfort from therapeutic agents. In the present study, the waste shedding of Dolichophis caspius (Hazer snake, bozyoruk) which has high keratin content and widely distributed was evaluated as a drug carrier biomaterial for the first time. D-Panthenol, which is commonly used in wound healing, was loaded on three different parts of the untreated waste snake skin, dorsal scale, ventral scale and hinge, and its release properties were investigated. Average drug loading capacities for the dorsal scale, ventral scale and hinge portions, were recorded as 2.07±0.13%, 1.28%±0.04% and 1.77±0.95%. The release was measured by taking sample for every hour at least for 24 hours. In the first hour, 46.67% of the drug was released in the dorsal scale, 80.09% in the ventral scale and 69.85% in the hinge portion. Based on these results, especially the dorsal scale part was developed in future studies and it was revealed that it is a potential biomaterial for controlled drug release.

Kaynakça

  • [1] Davoodi P, Lee LY, Xu Q, Sunil V, Sun Y, Soh S, (2018). Drug delivery systems for programmed and on-demand release Advenced Drug Delivery Reviews, 132, 104-138.
  • [2] Park, K. (2014). The controlled drug delivery systems: Past forward and future back, Journal of control release, 190, 3-8.
  • [3] McKittrick, J., Phen, P. Y., Bodde, S. G., Yang, W., Novitskaya, E. E. ve Meyers M. A. (2012). The structure, functions, and mechanical properties of keratin, JOM, 64, 4, 449-468.
  • [4] Coulombe, P. A. ve Omary, M, B. (2002). ‘Hard’ and ‘soft’ principles defining the structure, function and regulation of keratin intermediate filaments, Current Opinion in Cell Biology, 14, 1, 110-122.
  • [5] Wang, B., Yang, W., McKittrick, J., ve Meyer, M. A. (2016). Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration, Progress in Materials Science, 76, 229-318.
  • [6] Herrmann, H.ve Aebi U. (2004). Intermediate filaments: molecular structure, assembly mechanism and functionally Integration into different intracellular scaffolds, Annual Revi of Biochemistry, 73, 749-789.
  • [7] Konop, M., Rybak, M. ve Drapala, A. (2021). Keratin Biomaterials in Skin Wound Healing, an Old Player in Modern Medicine: A Mini Review, Biomaterials in Skin Wound Healing and Tissue Regeneration, 13, 12, 2029.
  • [8] Thomas, H., Conrads, A., Phan, P. H., van de Locht, M. ve Zahn, H. (1986). In vitor reconstitution of wool intermediate filaments, International Journal of Biological Macromolecules, 8, 5, 258-264.
  • [9] Loschke, F., Seltmann, K., Bouameur, J. E. ve Magin, T. M. (2015). Regulation of keratin network organization, Current Opinion in Cell Biology, 32, 56-64.
  • [10] Tachibana, A., Furuta, Y., Takeshima, H., Tanabe, T. ve Yamauchi, K. (2002). Fabrication of wool keratin sponge scaffolds for long-term cell cultivation, Journal of Biotechnology, 93, 2, 165-170.
  • [11] Rouse, J. G. ve Van Dyke M. E. (2010). A review of keratin-based biomaterials for biomedical applications, Materials, 3, 2, 999-1014.
  • [12] Vasconcelos, A. ve Cavaco-Paulo, A. (2013). The use of keratin in biomedical applications, Current Cancer Drug Targets, 14, 5, 612-619.
  • [13] Chilakamarry, C. R., Mahmood, S., Saffe, S. N. B. M., Arifin, M. A. B., Gupta, A., Sikkandar, M. Y., Begum, S. S. ve Narasaiah, B. (2021). Extraction and application of keratin from natural resources: a review, 3 Biotech, 11, 5, 220.
  • [14] Guo, H., Pan, S.J., Yin, X.C., He, Y.F., Li, T. ve Wang, R.M. (2015). pH-sensitive keratin-based polymer hydrogel and its controllable drug-release behaviour, Journal of Applied Polymer Science, 132, 41572.
  • [15] Yin, X.-C., Li, F.-Y., He, Y.-F. ve Wang, R.-M. (2013). Study on effective extraction of chicken feather keratins and their films for controlling drug release, Biomaterials Science, 1, 5, 528-536.
  • [16] Gong, X., Dang, G., Guo, J., Liu, Y. ve Gong, Y. (2020). A sodium alginate/feather keratin composite fiber with skin-core structure as the carrier for sustained drug release, International Journal of Biological Macromolecules, 155, 386-392.
  • [17] Nayak, K.K. ve Gupta, P. (2017). Study of the keratin-based therapeutic dermal patches for the delivery of bioactive molecules for wound treatment, Materials Science and Engineering: C, 77, 1088-1097.
  • [18] Cao, Y., Yao, Y., Li, Y., Yang, X., Cao, Z. ve Yang, G. (2019). Tunable keratin hydrogel based on disulfide shuffling strategy for drug delivery and tissue engineering, Journal of Colloid and Interface Science, 544, 121-129.
  • [19] Sun, Z., Yi, Z., Zhang, H., Ma, X., Su, W., Sun, X. ve Li, X. (2017). Bio-responsive alginate-keratin composite nanogels with enhanced drug loading efficiency for cancer therapy, Carbohydrate Polymers, 175, 159-169.
  • [20] Liu, P., Wu, Q., Li, Y., Li, P., Yuan, J., Meng, X. ve Xiao, Y. (2019). DOX-Conjugated Keratin Nanoparticles for pH-Sensitive Drug Delivery, Colloids and Surfaces B: Biointerfaces, 181, 1012-1018.
  • [21] Tomblyn, S., Pettit Kneller, E. L., Walker, S. J., Ellenburg, M. D., Kowalczewski, C. J., Van Dyke, M., Burnett, L. ve Saul, J. M. (2015). Keratin hydrogel carrier system for simultaneous delivery of exogenous growth factors and muscle progenitor cells, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 104(5), 864-879.
  • [22] Roy, D. C., Tomblyn, S., Isaac, K., M., Kowalczewski, C. J., Burmeister, D. M., Burnett, L. R. ve Christy, R. J. (2016). Ciprofloxacin-loaded keratin hydrogels reduce infection and support healing in a porcine partial-thickness thermal burn, Wound Repair and Regeneration, 24, 4, 657-668.
  • [23] Sadeghi, S., Nourmohammadi, J., Ghaee, A. ve Soleimani, N. (2019). Carboxymethyl cellulose-human hair keratin hydrogel with controlled clindamycin release as antibacterial wound dressing, International Journal of Biological Macromolecules, 147, 1239-1247.
  • [24] Cheng, Z., Chen, X, Zhai, D., Gao, F., Guo, T., Li, W., Hao, S., Ji, J, ve Wang, B. (2018). Development of keratin nanoparticles for controlled gastric mucoadhesion and drug release, Journal Nanobiotechnology, 16, 1-13.
  • [25] Ghaffari, R., Eslahi, N., Tamjid, E. ve Simchi, A. (2018). Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery, ACS Applied Materials & Interfaces, 10, 23, 19336-19346.
  • [26] Tran, C. D. ve Mututuvari, T. M. (2015). Cellulose, Chitosan, and Keratin Composite Materials, Controlled Drug Release. Langmuir, 31, 4, 1516-1526.
  • [27] Martella, E., Ferroni, C., Guerrini, A., Ballestri, M., Columbaro, M., Santi, S., Sotgiu, G., Serra, M., Donati, D., Lucarelli, E., Varchi, G. ve Duchi, S. (2018). Functionalized Keratin as Nanotechnology-Based Drug Delivery System for the Pharmacological Treatment of Osteosarcoma, International Journal of Molecular Sciences, 19, 11, 3670-.
  • [28] Foglietta, F., Spagnoli, G. C., Muraro, Manuele G., Ballestri, M., Guerrini, A., Ferroni, C., Aluigi, A., Sotgiu, G. ve Varchi, G. (2018). Anticancer activity of paclitaxel-loaded keratin nanoparticles in two-dimensional and perfused three-dimensional breast cancer models, International Journal of Nanomedicine, 13, 4847-4867.
  • [29] Aluigi, A., Ballestri, M., Guerrini, A., Sotgiu, G., Ferroni, C., Corticelli, F., Gariboldi, M. B., Monti, E. ve Varchi, G. (2018). Organic solvent-free preparation of keratin nanoparticles as doxorubicin carriers for antitumour activity, Materials Science and Engineering: C, 90, 476-484.
  • [30] Posati, T., Giuri, D., Nocchetti, M., Sagnella, A., Gariboldi, M., Ferroni, C., Sotgiu, G., Varchi, G., Zamboni, R. ve Aluigi, A. (2018). Keratin-hydrotalcites hybrid films for drug delivery applications, European Polymer Journal, 105, 177-185.
  • [31] Schifino, G., Gasparini, C., Drudi, S., Giannelli, M., Sotgiu, G., Posati, T., Zamboni, E. Treossi, E. Maccaferri, L. Giorgini, R. Mazzarro, V. Morandi, V. Palermo, R., Bertoldo, M. ve Aluigi, A. (2022). Keratin/Polylactic acid/graphene oxide composite nanofibers for drug delivery, Internatonal Journal of Pharmaceutics, 623, 121888.
  • [32] Nakata, R., Osumi, Y., Miyagawa, S., Tachibana, A. ve Tanabe, T. (2015). Preparation of keratin and chemically modified keratin hydrogels and their evaluation as cell substrate with drug releasing ability, Journal of Bioscience and Bioengineering, 120, 1, 111-116.
  • [33] Guidotti, G., Soccio, M., Bondi, E., Posati, T., Sotgiu, G., Zamboni, R., Torreggiani, A., Corticelli, F., Lotti, N. ve Aluigi, A. (2021). Effects of the blending ratio on the design of keratin/poly(butylene succinate) nanofibers for drug delivery applications, Biomolecules, 11, 8, 1194.
  • [34] Deng, X., Gould, M. ve Ali, M. A. (2021). Fabrication and characterisation of melt-extruded chitosan/keratin/PCL/PEG drug-eluting sutures designed for wound healing, Materials Science and Engineering: C, 120, 111696.
  • [35] Webb, M. E., Smith, A.,G. ve Abell, C. (2004). Biosynthesis of pantothenate, Natural Product Reports, 21, 6, 695.
  • [36] Vakilian, S., Jamshidi-adegani, F., Al-Shidhani, S., Anwar, M. U., Al-Harrasi, R., Al-Wahaibi, N., Qureshi, A., Alyaqoobi, S., Al-Amri, I., Al-Harrasi, A. ve Al-Hashmi, S. (2019). A Keratin-based biomaterial as a promising dresser for skin wound healing, Wound Medicine, 25, 1, 100155.

Atık Yılan Gömleğinin Taşıyıcı Sistem Olarak Değerlendirilmesi ve D-Panthenol’ün in Vitro Salımı

Yıl 2023, , 99 - 106, 30.12.2023
https://doi.org/10.29002/asujse.1298383

Öz

Kolajen, ipek ve keratin gibi biyomoleküller sahip oldukları birçok eşsiz özellikleri sayesinde yara iyileştirme ve ilaç taşıma sistemleri olarak medikal alanda sıkça tercih edilmektedir. Özellikle tüy, toynak, saç ve yünde bulunan, güçlü bir yapısal protein olan keratin bazlı materyaller, nantoksik ve biyouyumlu olmalarından dolayı ilaç salımı amaçlı tercih edilmektedir. Fakat yapısal protein olarak keratin içeren yılan gömleği için ilaç salımı üzerine herhangi bir çalışma yapılmamıştır. Kontrollü ilaç salımı, terapötik ajanlardan maksimum fayda sağlanması, minimum zarar görülmesi ve hasta konforu açısından oldukça önemlidir. Mevcut çalışmada, yüksek keratin içeriğine sahip ve oldukça geniş bir yayılım gösteren Dolichophis caspius’ un (Hazer yılanı, bozyörük) atık gömleği ilk kez ilaç taşıyıcı biyomalzeme olarak değerlendirilmiştir. Hiçbir işlem görmemiş atık yılan derisinin dorsal ölçek, ventral ölçek ve menteşe olmak üzere üç farklı kısmına, yara iyileşmesinde yaygın olarak kullanılan D-Panthenol yüklenmiş ve salım özellikleri araştırılmıştır. Sırasıyla dorsal ölçek, ventral ölçek ve menteşe kısımları için ortalama ilaç yükleme kapasiteleri: %2,07±0,13, %1,28±0,04, %1,77±0,95 olarak kaydedilmiştir. Salım 24 saat boyunca her saat başı örnek alınıp ölçüm yapılarak izlenmiştir. İlk 1 saatte dorsal ölçekte ilacın %46.67’si, ventral ölçekte %80.09’u ve menteşe kısmında %69.85’i salınmıştır. Bu sonuçlara dayanarak özellikle dorsal ölçek kısmının ileriki çalışmalarda geliştirilerek kontrollü ilaç salımı için potansiyel bir biyomalzeme olduğu ortaya konulmuştur.

Teşekkür

Yazarlar, Aksaray Üniversitesi Bilimsel ve Teknolojik Uygulama ve Araştırma Merkezi tarafından sağlanan teknik desteğe teşekkür eder. Araştırma görevlisi Bahar Akyüz Yılmaz’a yardımından dolayı teşekkür eder.

Kaynakça

  • [1] Davoodi P, Lee LY, Xu Q, Sunil V, Sun Y, Soh S, (2018). Drug delivery systems for programmed and on-demand release Advenced Drug Delivery Reviews, 132, 104-138.
  • [2] Park, K. (2014). The controlled drug delivery systems: Past forward and future back, Journal of control release, 190, 3-8.
  • [3] McKittrick, J., Phen, P. Y., Bodde, S. G., Yang, W., Novitskaya, E. E. ve Meyers M. A. (2012). The structure, functions, and mechanical properties of keratin, JOM, 64, 4, 449-468.
  • [4] Coulombe, P. A. ve Omary, M, B. (2002). ‘Hard’ and ‘soft’ principles defining the structure, function and regulation of keratin intermediate filaments, Current Opinion in Cell Biology, 14, 1, 110-122.
  • [5] Wang, B., Yang, W., McKittrick, J., ve Meyer, M. A. (2016). Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration, Progress in Materials Science, 76, 229-318.
  • [6] Herrmann, H.ve Aebi U. (2004). Intermediate filaments: molecular structure, assembly mechanism and functionally Integration into different intracellular scaffolds, Annual Revi of Biochemistry, 73, 749-789.
  • [7] Konop, M., Rybak, M. ve Drapala, A. (2021). Keratin Biomaterials in Skin Wound Healing, an Old Player in Modern Medicine: A Mini Review, Biomaterials in Skin Wound Healing and Tissue Regeneration, 13, 12, 2029.
  • [8] Thomas, H., Conrads, A., Phan, P. H., van de Locht, M. ve Zahn, H. (1986). In vitor reconstitution of wool intermediate filaments, International Journal of Biological Macromolecules, 8, 5, 258-264.
  • [9] Loschke, F., Seltmann, K., Bouameur, J. E. ve Magin, T. M. (2015). Regulation of keratin network organization, Current Opinion in Cell Biology, 32, 56-64.
  • [10] Tachibana, A., Furuta, Y., Takeshima, H., Tanabe, T. ve Yamauchi, K. (2002). Fabrication of wool keratin sponge scaffolds for long-term cell cultivation, Journal of Biotechnology, 93, 2, 165-170.
  • [11] Rouse, J. G. ve Van Dyke M. E. (2010). A review of keratin-based biomaterials for biomedical applications, Materials, 3, 2, 999-1014.
  • [12] Vasconcelos, A. ve Cavaco-Paulo, A. (2013). The use of keratin in biomedical applications, Current Cancer Drug Targets, 14, 5, 612-619.
  • [13] Chilakamarry, C. R., Mahmood, S., Saffe, S. N. B. M., Arifin, M. A. B., Gupta, A., Sikkandar, M. Y., Begum, S. S. ve Narasaiah, B. (2021). Extraction and application of keratin from natural resources: a review, 3 Biotech, 11, 5, 220.
  • [14] Guo, H., Pan, S.J., Yin, X.C., He, Y.F., Li, T. ve Wang, R.M. (2015). pH-sensitive keratin-based polymer hydrogel and its controllable drug-release behaviour, Journal of Applied Polymer Science, 132, 41572.
  • [15] Yin, X.-C., Li, F.-Y., He, Y.-F. ve Wang, R.-M. (2013). Study on effective extraction of chicken feather keratins and their films for controlling drug release, Biomaterials Science, 1, 5, 528-536.
  • [16] Gong, X., Dang, G., Guo, J., Liu, Y. ve Gong, Y. (2020). A sodium alginate/feather keratin composite fiber with skin-core structure as the carrier for sustained drug release, International Journal of Biological Macromolecules, 155, 386-392.
  • [17] Nayak, K.K. ve Gupta, P. (2017). Study of the keratin-based therapeutic dermal patches for the delivery of bioactive molecules for wound treatment, Materials Science and Engineering: C, 77, 1088-1097.
  • [18] Cao, Y., Yao, Y., Li, Y., Yang, X., Cao, Z. ve Yang, G. (2019). Tunable keratin hydrogel based on disulfide shuffling strategy for drug delivery and tissue engineering, Journal of Colloid and Interface Science, 544, 121-129.
  • [19] Sun, Z., Yi, Z., Zhang, H., Ma, X., Su, W., Sun, X. ve Li, X. (2017). Bio-responsive alginate-keratin composite nanogels with enhanced drug loading efficiency for cancer therapy, Carbohydrate Polymers, 175, 159-169.
  • [20] Liu, P., Wu, Q., Li, Y., Li, P., Yuan, J., Meng, X. ve Xiao, Y. (2019). DOX-Conjugated Keratin Nanoparticles for pH-Sensitive Drug Delivery, Colloids and Surfaces B: Biointerfaces, 181, 1012-1018.
  • [21] Tomblyn, S., Pettit Kneller, E. L., Walker, S. J., Ellenburg, M. D., Kowalczewski, C. J., Van Dyke, M., Burnett, L. ve Saul, J. M. (2015). Keratin hydrogel carrier system for simultaneous delivery of exogenous growth factors and muscle progenitor cells, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 104(5), 864-879.
  • [22] Roy, D. C., Tomblyn, S., Isaac, K., M., Kowalczewski, C. J., Burmeister, D. M., Burnett, L. R. ve Christy, R. J. (2016). Ciprofloxacin-loaded keratin hydrogels reduce infection and support healing in a porcine partial-thickness thermal burn, Wound Repair and Regeneration, 24, 4, 657-668.
  • [23] Sadeghi, S., Nourmohammadi, J., Ghaee, A. ve Soleimani, N. (2019). Carboxymethyl cellulose-human hair keratin hydrogel with controlled clindamycin release as antibacterial wound dressing, International Journal of Biological Macromolecules, 147, 1239-1247.
  • [24] Cheng, Z., Chen, X, Zhai, D., Gao, F., Guo, T., Li, W., Hao, S., Ji, J, ve Wang, B. (2018). Development of keratin nanoparticles for controlled gastric mucoadhesion and drug release, Journal Nanobiotechnology, 16, 1-13.
  • [25] Ghaffari, R., Eslahi, N., Tamjid, E. ve Simchi, A. (2018). Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery, ACS Applied Materials & Interfaces, 10, 23, 19336-19346.
  • [26] Tran, C. D. ve Mututuvari, T. M. (2015). Cellulose, Chitosan, and Keratin Composite Materials, Controlled Drug Release. Langmuir, 31, 4, 1516-1526.
  • [27] Martella, E., Ferroni, C., Guerrini, A., Ballestri, M., Columbaro, M., Santi, S., Sotgiu, G., Serra, M., Donati, D., Lucarelli, E., Varchi, G. ve Duchi, S. (2018). Functionalized Keratin as Nanotechnology-Based Drug Delivery System for the Pharmacological Treatment of Osteosarcoma, International Journal of Molecular Sciences, 19, 11, 3670-.
  • [28] Foglietta, F., Spagnoli, G. C., Muraro, Manuele G., Ballestri, M., Guerrini, A., Ferroni, C., Aluigi, A., Sotgiu, G. ve Varchi, G. (2018). Anticancer activity of paclitaxel-loaded keratin nanoparticles in two-dimensional and perfused three-dimensional breast cancer models, International Journal of Nanomedicine, 13, 4847-4867.
  • [29] Aluigi, A., Ballestri, M., Guerrini, A., Sotgiu, G., Ferroni, C., Corticelli, F., Gariboldi, M. B., Monti, E. ve Varchi, G. (2018). Organic solvent-free preparation of keratin nanoparticles as doxorubicin carriers for antitumour activity, Materials Science and Engineering: C, 90, 476-484.
  • [30] Posati, T., Giuri, D., Nocchetti, M., Sagnella, A., Gariboldi, M., Ferroni, C., Sotgiu, G., Varchi, G., Zamboni, R. ve Aluigi, A. (2018). Keratin-hydrotalcites hybrid films for drug delivery applications, European Polymer Journal, 105, 177-185.
  • [31] Schifino, G., Gasparini, C., Drudi, S., Giannelli, M., Sotgiu, G., Posati, T., Zamboni, E. Treossi, E. Maccaferri, L. Giorgini, R. Mazzarro, V. Morandi, V. Palermo, R., Bertoldo, M. ve Aluigi, A. (2022). Keratin/Polylactic acid/graphene oxide composite nanofibers for drug delivery, Internatonal Journal of Pharmaceutics, 623, 121888.
  • [32] Nakata, R., Osumi, Y., Miyagawa, S., Tachibana, A. ve Tanabe, T. (2015). Preparation of keratin and chemically modified keratin hydrogels and their evaluation as cell substrate with drug releasing ability, Journal of Bioscience and Bioengineering, 120, 1, 111-116.
  • [33] Guidotti, G., Soccio, M., Bondi, E., Posati, T., Sotgiu, G., Zamboni, R., Torreggiani, A., Corticelli, F., Lotti, N. ve Aluigi, A. (2021). Effects of the blending ratio on the design of keratin/poly(butylene succinate) nanofibers for drug delivery applications, Biomolecules, 11, 8, 1194.
  • [34] Deng, X., Gould, M. ve Ali, M. A. (2021). Fabrication and characterisation of melt-extruded chitosan/keratin/PCL/PEG drug-eluting sutures designed for wound healing, Materials Science and Engineering: C, 120, 111696.
  • [35] Webb, M. E., Smith, A.,G. ve Abell, C. (2004). Biosynthesis of pantothenate, Natural Product Reports, 21, 6, 695.
  • [36] Vakilian, S., Jamshidi-adegani, F., Al-Shidhani, S., Anwar, M. U., Al-Harrasi, R., Al-Wahaibi, N., Qureshi, A., Alyaqoobi, S., Al-Amri, I., Al-Harrasi, A. ve Al-Hashmi, S. (2019). A Keratin-based biomaterial as a promising dresser for skin wound healing, Wound Medicine, 25, 1, 100155.
Toplam 36 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sentetik Biyoloji
Bölüm Araştırma Makalesi
Yazarlar

Betül Aktaş 0000-0001-9235-7178

Lalehan Akyüz 0000-0001-8548-3037

Murat Kaya 0000-0001-6954-2703

Yayımlanma Tarihi 30 Aralık 2023
Gönderilme Tarihi 17 Mayıs 2023
Kabul Tarihi 2 Temmuz 2023
Yayımlandığı Sayı Yıl 2023

Kaynak Göster

APA Aktaş, B., Akyüz, L., & Kaya, M. (2023). Atık Yılan Gömleğinin Taşıyıcı Sistem Olarak Değerlendirilmesi ve D-Panthenol’ün in Vitro Salımı. Aksaray University Journal of Science and Engineering, 7(2), 99-106. https://doi.org/10.29002/asujse.1298383
Aksaray J. Sci. Eng. | e-ISSN: 2587-1277 | Period: Biannually | Founded: 2017 | Publisher: Aksaray University | https://asujse.aksaray.edu.tr