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Matencio, A.; Appleton, S.L.; Khazaei Monfared, Y.; , .; Caldera, F.; Cavalli, R.; Trotta, F. Cyclodextrin-Based Nanosponges and Proteins. Encyclopedia. Available online: https://encyclopedia.pub/entry/21740 (accessed on 03 July 2024).
Matencio A, Appleton SL, Khazaei Monfared Y,  , Caldera F, Cavalli R, et al. Cyclodextrin-Based Nanosponges and Proteins. Encyclopedia. Available at: https://encyclopedia.pub/entry/21740. Accessed July 03, 2024.
Matencio, Adrián, Silvia Lucia Appleton, Yousef Khazaei Monfared,  , Fabrizio Caldera, Roberta Cavalli, Francesco Trotta. "Cyclodextrin-Based Nanosponges and Proteins" Encyclopedia, https://encyclopedia.pub/entry/21740 (accessed July 03, 2024).
Matencio, A., Appleton, S.L., Khazaei Monfared, Y., , ., Caldera, F., Cavalli, R., & Trotta, F. (2022, April 14). Cyclodextrin-Based Nanosponges and Proteins. In Encyclopedia. https://encyclopedia.pub/entry/21740
Matencio, Adrián, et al. "Cyclodextrin-Based Nanosponges and Proteins." Encyclopedia. Web. 14 April, 2022.
Peer Reviewed
Cyclodextrin-Based Nanosponges and Proteins

Cyclodextrin-based nanosponges (CD-NSs) have gained importance in drug delivery in the last years due to their easy synthesis and versatility. However, their use as carriers for the delivery of macromolecules such as proteins is less known and sometimes difficult to consider. In this entry, the authors summarize and highlight the multiple possibilities of CD-NSs to deliver active proteins, improving their activity or stability. Starting with a brief description of CD-NSs and their characteristics, the entry will be focused on several proteins, such as (1) Lipase, (2) Insulin and (3) Nisin, for chemical or pharmaceutical applications. The revised results demonstrated that CD-NSs can generate different and interesting applications with proteins. These results could be added to their uses with small drugs, being an interesting alternative for protein delivery and applicability. 

cyclodextrin based nanosponges protein enzyme Lipase Peroxidase Insulin Nisin
Although novel drugs still arrive on the market every day, they usually present problems concerning their solubility and stability. For years, the use of cyclodextrins (CDs) to carry small drugs has been exploited. CDs are well-known to the scientific community for their uses in solubilizing poor-soluble drugs [1][2][3]. Chemically, CDs are cone-shaped oligosaccharides obtained from starch with α-(1,4) linked glucose units. The most common CDs are the natural derivatives with six, seven and eight glucose units called α, β and γ-CD, respectively. The CD ring is a conical cylinder of an amphiphilic nature, with a hydrophilic outer layer (formed by the hydroxyl groups) and a lipophilic cavity [4]. Classically, poorly-soluble drugs are complexed with CD, creating the so-called “inclusion complex”, which increases its solubility, stability or bioactivity [5][6][7].
In some cases, their capacity lacks in efficiency due to the complex structure of the drug or the desire of different profiles (e.g., slow release), and different materials have been prepared to improve their properties, such as the cited Cyclodextrin-based Nanosponge (CD-NS), an innovative cross-linked polymer with a three-dimensional network and a tunable structure with crystalline, amorphous or spherical structure and possessing good swelling properties [8]. Recent reviews [9][10][11][12] indicate their wide potential and negligible toxicity [13][14], increasing their biocapacities in several applications, including the ability to (i) improve the apparent solubility of poorly soluble drugs, (ii) modulate drug release and activity, (iii) protect drugs against several agents, (iv) enhance bioactivities, (v) absorb contaminants or deliver the drug, etc.
In recent years, the use of proteins in industry or in therapy has increased, creating an interesting atmosphere for CD-NS, to study all of the positive effects they have on both small molecules and larger ones. A specific case could be the use of CDs with proteins to prevent their aggregation or crystallization of amorphous stabilizers during freezing, even acting as artificial chaperons [14][15]. However, the entire protein cannot be captured by CDs, only by different motifs, which creates different protection zones. In this context, the supramolecular form of CD-NS could generate some benefits by capturing the entire protein within its 3D network.
This entry will try to summarize, explain and emphasize, simply but scientifically, the different opportunities and novelties of CD-NS in protein stabilization using different examples; Dioxygenase [16], Bovine Serum Albumin [17], Lipase [18], Peroxidase [19], Lysozyme [20], Insulin [21] and Nisin [22][23] after explaining the types and characteristics of different CD-NSs for eventual use of the reader.

References

  1. Jansook, P.; Ogawa, N.; Loftsson, T. Cyclodextrins: Structure, Physicochemical Properties and Pharmaceutical Applications. Int. J. Pharm. 2018, 535, 272–284.
  2. Brewster, M.E.; Loftsson, T. Cyclodextrins as Pharmaceutical Solubilizers. Adv. Drug Deliv. Rev. 2007, 59, 645–666.
  3. Santos, C.I.A.V.; Ribeiro, A.C.F.; Esteso, M.A. Drug Delivery Systems: Study of Inclusion Complex Formation between Methylxanthines and Cyclodextrins and Their Thermodynamic and Transport Properties. Biomolecules 2019, 9, 196.
  4. Kurkov, S.V.; Loftsson, T. Cyclodextrins. Int. J. Pharm. 2013, 453, 167–180.
  5. Matencio, A.; Bermejo-Gimeno, M.J.; García-Carmona, F.; López-Nicolás, J.M. Separating and Identifying the Four Stereoisomers of Methyl Jasmonate by RP-HPLC and Using Cyclodextrins in a Novel Way. Phytochem. Anal. 2017, 28, 151–158.
  6. Matencio, A.; Caldera, F.; Pedrazzo, A.R.; Khazaei Monfared, Y.; Dhakar, N.K.; Trotta, F. A Physicochemical, Thermodynamical, Structural and Computational Evaluation of Kynurenic Acid/Cyclodextrin Complexes. Food Chem. 2021, 356, 129639.
  7. López-Nicolás, J.M.; García-Carmona, F. Effect of Hydroxypropyl-β-Cyclodextrin on the Aggregation of (E)-Resveratrol in Different Protonation States of the Guest Molecule. Food Chem. 2010, 118, 648–655.
  8. Cavalli, R.; Trotta, F.; Tumiatti, W. Cyclodextrin-Based Nanosponges for Drug Delivery. J. Incl. Phenom. Macrocycl. Chem. 2006, 56, 209–213.
  9. Sherje, A.P.; Dravyakar, B.R.; Kadam, D.; Jadhav, M. Cyclodextrin-Based Nanosponges: A Critical Review. Carbohydr. Polym. 2017, 173, 37–49.
  10. Swaminathan, S.; Cavalli, R.; Trotta, F. Cyclodextrin-Based Nanosponges: A Versatile Platform for Cancer Nanotherapeutics Development. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2016, 8, 579–601.
  11. Krabicová, I.; Appleton, S.L.; Tannous, M.; Hoti, G.; Caldera, F.; Rubin Pedrazzo, A.; Cecone, C.; Cavalli, R.; Trotta, F. History of Cyclodextrin Nanosponges. Polymers 2020, 12, 1122.
  12. Mane, P.T.; Wakure, B.S.; Wakte, P.S. Cyclodextrin Based Nanosponges: A Multidimensional Drug Delivery System and Its Biomedical Applications. Curr. Drug Deliv. 2021, 18, 1467–1493.
  13. Shende, P.; Kulkarni, Y.A.; Gaud, R.S.; Deshmukh, K.; Cavalli, R.; Trotta, F.; Caldera, F. Acute and Repeated Dose Toxicity Studies of Different β-Cyclodextrin-Based Nanosponge Formulations. J. Pharm. Sci. 2015, 104, 1856–1863.
  14. Matencio, A.; Guerrero-Rubio, M.A.; Caldera, F.; Cecone, C.; Trotta, F.; García-Carmona, F.; López-Nicolás, J.M. Lifespan Extension in Caenorhabditis Elegans by Oxyresveratrol Supplementation in Hyper-Branched Cyclodextrin-Based Nanosponges. Int. J. Pharm. 2020, 589, 119862.
  15. Serno, T.; Geidobler, R.; Winter, G. Protein Stabilization by Cyclodextrins in the Liquid and Dried State. Adv. Drug Deliv. Rev. 2011, 63, 1086–1106.
  16. Nardo, G.D.; Roggero, C.; Campolongo, S.; Valetti, F.; Trotta, F.; Gilardi, G. Catalytic Properties of Catechol 1,2-Dioxygenase from Acinetobacter Radioresistens S13 Immobilized on Nanosponges. Dalton Trans. 2009, 33, 6507–6512.
  17. Swaminathan, S.; Cavalli, R.; Trotta, F.; Ferruti, P.; Ranucci, E.; Gerges, I.; Manfredi, A.; Marinotto, D.; Vavia, P.R. In Vitro Release Modulation and Conformational Stabilization of a Model Protein Using Swellable Polyamidoamine Nanosponges of β-Cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 2010, 68, 183–191.
  18. Boscolo, B.; Trotta, F.; Ghibaudi, E. High Catalytic Performances of Pseudomonas Fluorescens Lipase Adsorbed on a New Type of Cyclodextrin-Based Nanosponges. J. Mol. Catal. B Enzym. 2010, 62, 155–161.
  19. Wajs, E.; Caldera, F.; Trotta, F.; Fragoso, A. Peroxidase-Encapsulated Cyclodextrin Nanosponge Immunoconjugates as a Signal Enhancement Tool in Optical and Electrochemical Assays. Analyst 2013, 139, 375–380.
  20. Deshmukh, K.; Tanwar, Y.S.; Sharma, S.; Shende, P.; Cavalli, R. Functionalized Nanosponges for Controlled Antibacterial and Antihypocalcemic Actions. Biomed. Pharmacother. 2016, 84, 485–494.
  21. Appleton, S.L.; Tannous, M.; Argenziano, M.; Muntoni, E.; Rosa, A.C.; Rossi, D.; Caldera, F.; Scomparin, A.; Trotta, F.; Cavalli, R. Nanosponges as Protein Delivery Systems: Insulin, a Case Study. Int. J. Pharm. 2020, 590, 119888.
  22. Khazaei Monfared, Y.; Mahmoudian, M.; Cecone, C.; Caldera, F.; Zakeri-Milani, P.; Matencio, A.; Trotta, F. Stabilization and Anticancer Enhancing Activity of the Peptide Nisin by Cyclodextrin-Based Nanosponges against Colon and Breast Cancer Cells. Polymers 2022, 14, 594.
  23. Khazaei Monfared, Y.; Mahmoudian, M.; Hoti, G.; Caldera, F.; López Nicolás, J.M.; Zakeri-Milani, P.; Matencio, A.; Trotta, F. Cyclodextrin-Based Nanosponges as Perse Antimicrobial Agents Increase the Activity of Natural Antimicrobial Peptide Nisin. Pharmaceutics 2022, 14, 685.
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