Optimization of Particle Size Distribution with Gaussian Analysis of Albumin Microcarriers Cross-linked by Natural Phenolic Compounds

Year 2025, Early View, 1 - 1

Sultan Duman , Oğuz Akpolat , Fatma Ayhan

https://doi.org/10.35378/gujs.1273711

Abstract

The biodegradation of albumin into natural products and nontoxicity besides its antigenicity has many advantages in controlled drug delivery of therapeutic agents. A bifunctional covalent bonding agent, glutaraldehyde is extensively used for linking amine groups of albümin microparticles/microcarriers (AlbMC’s). But its cytotoxicity and the rapid calcification of the glutaraldehyde-treated tissue limit the use of glutaraldehyde. Phenolic compound showed non-covalent and covalent chemical interactions with proteins. The objective of this research is to prepare three different natural phenolic compound cross-linked/stabilized AlbMC’s and estimate the cross-linker concentration which is giving narrow size distributions since it is important to gain higher surface area. The influence of qallic acid (GA), tannic acid (TA) and quercetin concentrations on AlbMC’s size was investigated by Gaussian function analysis of microcarriers determined after optical micrograph measurements. Gallic acid (GA) stabilized AlbMC’s have 3.35  0.71 μm average mean size distribution while it was 3.56  0.71 μm for Quercetin and 3.71  0.69 μm for TA stabilized microcarrier formations. Average mean particle size distribution of AlbMC’s synthesized with synthetic cross-linker, glutaraldehyde was calculated as 5.12  0.50 μm. All statistical analysis were evaluated by MATLAB program. New approach for albumin microcarrier synthesis by using phenolic compounds as a cross-linker can be proposed as an alternative microcarrier preparation system with narrow size distributions.

Keywords

Albumin microcarrier, Natural cross-linker, Gallic acid, Tannic acid, Quercetin

Supporting Institution

Muğla Sıtkı Koçman University, Research Support and Funding Office

Project Number

20/108/08/1/2

Thanks

The authors would like to thank Muğla Sıtkı Koçman University, Research Support and Funding Office for funding this project with Project Number 20/108/08/1/2 and Prof. Dr. Hakan Ayhan for his insightful suggestions and careful reading of the manuscript.

References

• [1] Ramaiah, B., Nagaraja, S.H., Kapanigowda, U.G., Boggarapu, P.R., Subramanian, R., “High azithromycin concentration in lungs by way of bovine serum albümin microspheres as targeted drug delivery: lung targeting efficiency in albino mice”, DARU Journal of Pharmaceutical Sciences, 24(14): 1-11, (2016).
• [2] Tuncay, M., Calis, S., Kas, H.S., Ercan, M.T., Peksoy, I., Hincal, A.A., “In vitro and in vivo evaluation of diclofenac sodium loaded album in microspheres”, Journal of Microencapsulation, 17(2): 145-155, (2000).
• [3] Urs, A.V.R., Kavitha, K., Sockan, G.N., “Albumın mıcrospheres: an unique system as drug delivery carriers for Non steroidal anti-inflammatory drugs”, International Journal of Pharmaceutical Sciences Review and Research, 5(2): 9-17, December (2010).
• [4] Mutalikdesai, A., Zoabi, A., Kumar, V. B., Abu-Reziq, R., Hassner, A., Gedanken, A., “Enantioselective Separation of Racemic Tryptophan with Sonochemically Prepared Egg Albumin Microspheres”, ChemistrySelect, 3, 4004–4008, (2018).
• [5] Elsadek, B., Kratz F., “Impact of albumin on drug delivery - New applications on the horizon”, Journal of Controlled Release, 157(1): 4–28, (2012).
• [6] Thakkar, H., Kumar, R., Sharma, A., Mishra, K., Chuttani, K., Murthy, R.R., “Albumin Microspheres as Carriers for the Antiarthritic Drug Celecoxib”, AAPS PharmSciTech, 6(1): E65-73, (2005).
• [7] Damink, L.H.H.O., Dıjkstra, P.J., Luyn, M.J.A.V., Wachem, P.B.V., Nıeuwenhuis, P., Feijen, J., “Glutaraldehyde as a Crosslinking Agent for Collagen-based Biomaterials”, Journal of Materials Science: Materials in Medicine, 6: 460-472 (1995).
• [8] Pinheiro, A., Cooley, A., Liao, J., Prabhu, R., Elder, S., “Comparison of Natural Crosslinking Agents for the Stabilization of Xenogenic Articular Cartilage”, Journal of Orthopaedic Research, 34(6): 1037-46, June (2016).
• [9] MacAlister, S.L., “Investigating the Cytotoxic Mechanisms of Hepatotoxicity Induced by Xenobiotıcs And Their Metabolites”, PhD thesis, University of Toronto, Department of Pharmaceutical Sciences, (2013).
• [10] Crozier, A., Jaganath, I.B., Clifford, M.N., “Dietary Phenolics: Chemistry, Bioavailability and Effects on Health”, Natural Product Reports, 26: 1001-1043, (2009).
• [11] Mohammad-Beigi, H., Shojaosadati S.A., Morshedi, D., Arpanaei, A., Marvian, A.T., “Preparation and in vitro characterization of gallic acid-loaded human serum albumin nanoparticles”, Journal of Nanoparticle Research, 17: 167, (2015).
• [12] Fernandes F.H.A., Salgado H.R.N., “Gallic acid: Review of the Methods of Determination and Quantification, Critical Reviews in Analytical Chemistry, 46(3): 257-65, (2015).
• [13] Bozic, M., Gorgieva, S., Kokol, V., “Homogeneous and heterogeneous methods for laccase-mediated functionalization of chitosan by tannic acid and quercetin”, Carbohydrate Polymers, 89: 854-864, (2012).
• [14] Braidy, N., Jugder, B.E., Poljak, A., Jayasena, T., Nabavi, S.M., Sachdev, P., Grant, R., “Molecular Targets of Tannic Acid in Alzheimer's Disease”, Current Alzheimer Research, 14(8): 861-869, (2017).
• [15] Bentz, A.B., “A Review of Quercetin: Chemistry, Antioxidant Properties, and Bioavailability”, Journal of Young Investigators, 19: 10, (2009).
• [16] Formica, J.V., Regelson, W., “Review of the biology of quercetin and related bioflavonoids”, Food and Chemical Toxicology, 33(12): 1061-1080, (1995). [17] Nan, W., Ding, L., Chen, H., Khan, F.U., Yu, L., Sui, X., Shi, X., “Topical Use of Quercetin-Loaded Chitosan Nanoparticles Against Ultraviolet B Radiation”, Frontiers in Pharmacology, 9: 826, (2018).
• [18 Batiha, G.E.-S., Beshbishy, A.M., Ikram, M., Mulla, Z.S., Abd El-Hack, M.E., Taha, A.E., Algammal, A M., Elewa, Y.H.A., “The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin”, Foods, 9: 374, (2020).
• [19 Tang, S.M., Deng, X.T., Zhou, J., Li, Q.P., Ge, X.X., Miao, L., “Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects”, Biomedicine &. Pharmacotherapy, 121: 109604, (2020).
• [20 Adamczyk, B., Simon, J., Kitunen, V., Adamczyk, S., Smolander, A., “Tannins and Their Complex Interaction with Different Organic Nitrogen Compounds and Enzymes: Old Paradigms versus Recent Advances”, Chemistry Open, 6: 610-614, (2017).
• [21 Haslam, E., “Vegetable tannins – Lessons of a phytochemical lifetime”, Phytochemistry, 68: 2713-2721, (2007).
• [22 Hagerman, A.E., “Phenolic compounds in food and their effects on health I – Analysis, occurrence and chemistry”, ACS Symposium Series 506, Washington, D.C., 237–247, (1992).
• [23 Spencer, M.C., Cai, Y., Martin, R., Gaffney, S.H., Goulding, P.N., Magnolato, D., Lilley, T.H., Haslam, E., “Polyphenol complexation: some thoughts and observations”, Phytochemistry, 27: 2397-2409, (1988).
• [24 Rawel, H.M., Kroll, J., Hohl, U.C., “Model studies on reactions of plant phenols with whey Proteins”, Nahrung/Food, 45(2): 72-81, (2001).
• [25] Shavandi A., Bekhit A.E.A., Saeedi P., Izadifar, Z., Bekhit A.A., Khademhosseini, A., “Polyphenol uses in biomaterials engineering”, Biomaterials, 167: 91-106, (2018).
• [26 Zhang, X., Do, M.D., Casey, P., Sulistio, A., Qiao, G.G., Lundin, L., Lillford P., Kosaraju S., “Chemical Cross-Linking Gelatin with Natural Phenolic Compounds as Studied by High-Resolution NMR Spectroscopy”, Biomacromolecules, 11: 1125–1132, (2010).
• [27 Zhao, Y., Sun, Z., “Effects of gelatin-polyphenol and gelatin-genipin cross-linking on the structure of gelatin hydrogels”, International Journal of Food Properties, 20: S3, S2822–S2832, (2017).
• [28] Liu, W., Chen, S., Li, S., “Random loose packings of polydisperse adhesive microparticles with Gaussian size distribution”, Powder Technology, 357: 64–73, (2019).
• [29] Dytso, A., Bustin, R., Poor, H.V., Shamai, S., “Analytical properties of generalized Gaussian distributions”, Journal of Statistical Distributions and Applications, 5(6): 1-40, (2018).
• [30] Longo, W.E., Iwata, H., Lindheimer, T.A., Goldberg, E.P., “Preparation of Hydrophilic Albumin Microspheres Using Polymeric Dispersing Agents”, Journal of Pharmaceutical Sciences, 71(12): 1323-1328, December (1982).
• [31] Luftensteiner, C.P., Viernstein, H., “Statistical experimental design-based studies on placebo and mitoxantrone-loaded albumin microspheres”, International Journal of Pharmaceutics, 171: 87–99, (1998).
• [32] Gülsu, A., Ayhan, H., Ayhan, F., “Preparation and characterization of ketoprofen loaded albumin microspheres”, Turkish Journal of Biochemistry, 37(2): 120-128, (2012).
• [33] Joye I.J., McClements D.J, “Biopolymer-based Nanoparticles and Microparticles: Fabrication, Characterization, and Application”, Current Opinion in Colloid & Interface Science, 19: 417-427, (2014).
• [34] https://pubchem.ncbi.nlm.nih.gov/compound/Gallic-acid. Access date: 15.02.2023
• [35] https://pubchem.ncbi.nlm.nih.gov/compound/Tannic-acid. Access date: 15.02.2023
• [36 https://pubchem.ncbi.nlm.nih.gov/compound/Quercetin#section=Solubility. Access date: 09.02.2023
• [37] Zhan, M., Guo, M., Jiang, Y., Wang, X., “Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy”, International Journal of Molecular Sciences, 16: 14786-14807, (2015).
• [38] Labieniec, M., Gabryelak, T., “Interactions of tannic acid and its derivatives (ellagic and gallic acid) with calf thymus DNA and bovine serum albümin using spectroscopic method”, Journal of Photochemistry and Photobiology B: Biology, 82: 72-78, (2006).
• [39] Zhang, L., Liu, Y., Hua, X., Xua, M., Wang, Y., “Studies on interactions of pentagalloyl glucose, ellagic acid and gallic acid with bovine serum albumin: A spectroscopic analysis”, Food Chemistry, 15(324): 126872, (2020).