Cryochemical Formation of Drug Nanoforms: Approach to Directed Drug
Delivery and Controlled Drug Release1

Tatyana I. Shabatina1,2*, Yu.N.Morosov1,2, Irina V. Astashova3, Mikhail Ya.Melnikov1

Lomonosov Moscow State University, Department of Chemistry, Leninskie Gori build. 1/3
119991 Moscow, Russia
2
Bauman Moscow Technical State University, Faculty of Fundamental Sciences, 2-nd
Bauman Street, build.5, Moscow 105005, Russia
3
Lomonosov Moscow State University, Department of Mechanic and Mathematics; Moscow,119991, Russia
The use of medicinal substances in nanosized forms (nanoforms, nanoparticles) allows pharmaceuticalpreparations to increase their therapeutic effectiveness due to several factors: high specific surface areaof nanomaterials; high concentration of surface-active centers interacting with biological objects. In
the case of drug nanoforms even low concentrations of a bioactive substance can have a significant
therapeutic effect on living organisms. These facts lead pharmacists to use lower doses of active
components and in consequence to lower side toxic effects of pharmaceutical preparations innanoforms. It is known for many drug substances, which are commonly used nowadays, to be poorly
soluble in water, so they have insufficient bioavailability. Converting them into nanoforms will
increase the rate of dissolution and increased saturation solubility of drug nanocrystals rising theirbioavailability, and thus makes a significant contribution to their higher therapeutic efficiency. Some
physical and chemical methods can contribute to the formation of both pure drug nanoparticles andtheir ligand or polymer-covered nanoforms, which are characterized by higher stability.
Cryochemical modification is a powerful method of reducing the size of drug substances particles,changing their form and crystal structure in order to transfer them in nanoforms and improve theirpharmaceutical properties. An application of this method allowed us to obtain antibiotics nanocrystals
and their hybrid nanocomposites with metal particles. Antibacterial compositions were produced by
low temperature drug and metal vapors co-deposition or cryogenic freeze drying technique of mixed
water solutions containing silver or copper nanoparticles and antibacterial components dioxidine or
gentamicin [1, 2]. The thorough investigations TEM, electron microdiffraction, Fourier transformation
infrared spectroscopy (FTIR), UV absorption spectroscopy, X-ray diffraction, differential thermalanalysis (DTA) were made, It was shown that the hybrid compositions were including Ag and/or Cu
nanoparticles of 5-70 nm in diameter and nanoparticles of antibiotics of 50-250 nm in diameter. Drug
cryochemical forms possessed modified crystal structures and lower melting temperatures, New
cryoformed hybrid composites of nanosized metal and antibiotic particles demonstrates higher
antibacterial activity against E. coli 52, S.aureus 144, M. cyaneum 98, B. cereus 9 compared to theoriginal drug substance and individual metal nanoparticles.
The comprehensive mathematic models describing the different stages of cryomodification processes
developed will give us the base for finding of the optimal values of different physico-chemicalparameters for producing of drug nanoforms with desired therapeutic effects and bioavailability.
Acknowledgements. The work is financially supported by the State Scientific Program of the MSU
Development, MSU Interdisciplinary Grants for Scientific Schools, NSH – 2023-05-0026.
1. Shabatina, T.I.; Morosov, Y.N.; Soloviev, A.V.; Shabatin, A.V.; Vernaya, O.I.; Melnikov, M.Y. Cryochemical
Production of Drug Nanoforms: Particle Size and Crystal Phase Control of the Antibacterial Medication 2,3Quinoxalinedimethanol-1,4-dioxide(Dioxidine).
Nanomaterials
2021,
11,1588.
https://doi.org/10.3390/nano11061588

2. Shabatina, T.I.; Vernaya, O.I.; Melnikov, M.Y. Hybrid Nanosystems of Antibiotics with Metal Nanoparticles Novel Antibacterial Agents. Molecules 2023, 28, 1603. https://doi.org/10.3390/molecules28041603