Hydrogels and cryogels based on fmoc-phephe nanotubes as efficient carrier of active pharmaceutical ingredient

The drug delivery systems(DDS) fabricated via self-assembly of biocompatible nonalergic components is of great importance for treatment of chronic wounds and diseases. The benefit of the DDS composed of short sequence peptide derivative compare to polymeric DDS is absence of immunogenic response, formation of the hydrogel based on nanofibers quickly upon injection of solution of pharmaceutical active ingredient to a low molecular weight gelator with pH changing, Fmoc(Phe)3 hydrogels and other hydrogels were used for delivery of Desamethsone [1-5].

In this study inclusion of biologically active substances during the hydrogel formation via selfassembly of Fmoc(Phe)2 in situ was studied. We have shown that novel hydrazides and corresponding hydrazones containing piperidine or harmine heterocycle are very perspective pharmacutical substances[6-7].

Cryogels and hydrogels via self-organization Fmoc-(Phe)2 were prepared [5]. The kinetics of desorption of the substance a 3,4-dihydroxy-benzylidenhydrazide 2-methyl-3-(N-piperidinyl)propionic acid in 0.01M phosphate buffer was examined using UV spectrophotometery.

Thus, the maximum concentration of the biologically active substance was achieved within 5 hours at pH 5.8 and 7 and were equaled to 1.6 and 1.9 x 10-5 Mol/L, respectively. DDS of cryogels Fmoc(Phe)2 revealed the equilibrium concentration of desorbed substance of 3.11 and 3.47 x 10-5 Mol/L at pH 5.8 and 7.0, respectively. Three-fold increase of the 3,4-dihydroxy-benzylidenhydrazide 2-methyl- 3-(N-piperidinyl)propionic acid desorption from cryogel compare to the hydrogel with the same loading capacity of the drug can be attributed to high porosity of the scaffold.

The cryogel has a large surface area, from which the desorption of the substance takes place faster. It can be concluded that DDS of Fmoc(Phe)2, or other peptides can be loaded with various concentration of drug and one can also modulated the rate of release by change of morphology. Usage of circular dichroism allows to estimate the mechanism of self-organization upon addition of the drug and to evaluate a relative fraction of the drug that was not entrapped to the gel structure.

References:

1. Raymond, D. M., Abraham, B. L., Fujita, T., Watrous, M. J., Toriki, E. S., Takano, T., & Nilsson, B. L. (2019). Low-molecular-weight supramolecular hydrogels for sustained and localized in vivo drug delivery. ACS applied bio materials, 2(5), 2116-2124.
2. Abraham, B. L., Toriki, E. S., N’Dea, J. T., & Nilsson, B. L. (2020). Electrostatic interactions regulate the release of small molecules from supramolecular hydrogels. Journal of Materials Chemistry B, 8(30), 63666377.
3. Chronopoulou, L., Margheritelli, S., Toumia, Y., Paradossi, G., Bordi, F., Sennato, S., & Palocci, C. (2015). Biosynthesis and characterization of cross-linked Fmoc peptide-based hydrogels for drug delivery applications. Gels, 1(2), 179-193.
4. Yu, Z., Xu, Q., Dong, C., Lee, S. S., Gao, L., Li, Y., ... & Wu, J. (2015). Self-assembling peptide nanofibrous hydrogel as a versatile drug delivery platform. Current pharmaceutical design, 21(29), 43424354.
5. Berillo D., A. Yeskendir, Zh. Zharkinbekov, K. Raziyeva, and A. Saparov, Peptide-Based Drug Delivery Systems Review Medinica 2021
6. Berillo, D., Mattiasson, B., Galaev, I. Y., & Kirsebom, H. (2012). Formation of macroporous self-assembled hydrogels through cryogelation of Fmoc–Phe–Phe. Journal of colloid and interface science, 368(1), 226-230.
7. Berillo A. D, Dyusebaeva A. M. Antimicrobial and spazmolitic activity of hydazides of heterocyclic amines Saudi Pharmaceutical Journal 2021
8. R.B. Seidakhmetova, A. Amanzhan, E.E. Schultz, K.V. Goldaeva, D. Berillo, S.M. Adekenov Analgesic and antidepressent activity of Harmine hydrazone derivatives Journal of Asian Natural Products Research 2021 Хамметова А.Е., Шукирбекова А.Б., Искакова Р.М., Бекмуратова К.К.