Water-soluble nanoformulation of a hydrophobic anticancer Pt IV complex with a lonidamine-based ligand has been developed. Biodegradable nanocarriers (13 nm) obtained from poly( l -lactide-block-polyethylene glycol) star-shaped block copolymers were used to create the formulation. The loading of the active agent into nanoparticles was up to 3.7 wt.%, and the loading efficiency was up to 68%. It was shown that solubilization of the anticancer complex into polymeric nanoparticles did not lead to a significant decrease in its cytotoxicity. As the number of arms in the star-shaped block copolymers increased, the selectivity of the nanoformulations towards cancer cells tended to increase.

The study of the effect of iodine on the degradation of poly(ε-caprolactone) fibers has revealed a drastic decrease in their molecular weight upon 24 h exposure to a 10% iodine solution in ethanol. It has been assumed that the main mechanism of this degradation is alcoholysis which proceeds with an efficient rate constant of nearly 7.5 × 10–3 h–1

Исследован процесс полимеризации L-лактида под действием органического катализатора 1,8-диазабицикло[5.4.0]ундец-7-ена. Определены частные порядки реакции по мономеру и катализатору, рассчитана константа скорости полимеризации. Синтезированы перспективные для применения в медицине линейные поли- L -лактиды со среднемассовой молекулярной массой от 29 × 10 3 до 125 × 10 3 и индексом полидисперсности не выше 1.25. Показана возможность использования комбинации органокатализатора и гидроксилсодержащих инициаторов для синтеза звездообразного полилактида и амфифильного сополимера полилактид– блок –полиэтиленоксид.

The main goal of research is to study ring-opening polymerization of L-lactide in the presence of multifunctional alcohols in order to determine the optimal conditions for synthesis of star-shaped molecules of a predetermined well-defined structure, which is necessary for fine adjustment of material properties for various biomedical applications. The degree of polymerization of 3-, 4- and 6-arm star-shaped poly(L-lactides) varied from 10 to 100 monomer units per arm. It was found that under the same conditions polymerization rate and rate of initiation of co-initiator's hydroxyl groups can vary significantly depending on the structure and concentration of the selected alcohol. To prove the absence of cyclic, linear and comet-like structures in synthesized star-shaped PLLA, a variety of instrumental methods were used including GPC with triple detection, 1H NMR and MALDI. Study of properties and supramolecular structure of poly(L-lactides) using DSC and WAXS demonstrated that branching limits segmental mobility of the PLLA chains, especially for short arms, and hinders crystallization of star-shaped poly(L-lactides).

The polymerization of L-lactide mediated by the organic catalyst 1,8-diazabicyclo[5.4.0]undec-7-ene is studied. It is shown that the concentration of the catalyst affects not only the reaction rate, but also the molecular weight of the resulting polymers. Partial reaction orders with respect to the monomer and catalyst are determined, and the polymerization rate constant is calculated. Linear poly(L-lactides) with weight-average molecular weights from 29 × 103 to 125 × 103 and polydispersity below 1.25 promising for medical applications are synthesized. It is shown that combination of the organocatalyst with hydroxyl-containing initiators can be used for synthesis of the star-shaped polylactide and the amphiphilic copolymer polylactide–block–poly(ethylene oxide).

Qualitative differences in the nature of the electrorheological response of a detonation nanodiamonds suspensions in mineral oil depending on the type of particle surface functionaliza-tion were established from a number of rotational and oscillation tests. The type of modification and the chemical composition of the surface for particles of hydrogenated and carboxylated nanodiamonds were studied by infrared spectroscopy. Particles morphology and their structural organization in a mineral oil medium were studied by small-angle X-ray scattering method. It was found that suspensions of hydrogenated and carboxylated particles under an electric field exhibit an electrorheological and electrophoretic effects, respectively. The reasons for the electrophoretic motion of carboxylated nanodiamonds in a mineral oil medium were analyzed in comparison with the previously observed effect in the medium of weakly amphiphilic polydimethylsiloxane (silicon oil). The water content on the surface of both hydrogenated and carboxylated nanodiamond par-ticles was determined by Karl Fischer titration of suspensions. The correlation between the elec-trophoretic effect and the adsorbed water content on the surface of the particles was suggested. The method of rotational viscometry revealed the dependences of the static yield stress for sus-pensions filled with hydrogenated and carboxylated nanodiamonds at various electric field strength. The flow curves of the fluid filled with hydrogenated particles without and under an electric field were fitted by Bingham and Cho-Choi-Jhon rheological models. An analysis of the used models matching to practical results was performed. Based on the dependences of the stor-age and loss moduli on the deformation amplitude, a linear range of the viscoelastic properties of the fluid was revealed. An increase in the values of the storage and loss moduli, as well as a narrow-ing of the linear viscoelasticity range with an increase in the electric field strength was detected.

Stereolithography and DLP printing attract a lot of attention in medical field as techniques for fabrication of personalized implants and various medical devices. However, there is a lack of photo-curable resins for fabrication of biodegradable tissue engineering constructs and implants. In this work biodegradable UV-curable d,l-lactide oligomers are presented, which can be good candidates as resins for SLA and DLP 3D printing. Linear and star-shaped (3- and 6-arm) methacrylated d,l-lactide oligomers with different molecular weight are synthesized and cross-linked in various conditions. UV-curing is performed at elevated temperatures in the absence of any diluents and revealed formation of gel fraction, which has achieved 99%. The cross-linked materials demonstrate high tensile modulus (up to 1.8 GPa), suggesting the resins are perspective for fabrication of load-bearing implants.

Hyaluronic acid-based nanofiber scaffolds imitating the natural extracellular matrix, which is promising for use in tissue engineering, have been prepared by electrospinning. Hyaluronic acid is part of many organs and tissues; it is a biologically active component capable of being involved in cell proliferation and migration. The high viscosity of solutions of the macromolecular biopolymer significantly complicates the preparation of nanofiber scaffolds based on it. Rheological studies have made it possible to determine the solvent composition that contributes to a decrease in the viscosity of the spinning solution. The highest Newtonian viscosity of a 1% hyaluronic acid solution in water is 25 Pa s; in the case of using a mixture of ammonia hydrate (10%) and dimethylformamide at a ratio of 2 : 1, this parameter decreases to 1.147 Pa s. The use of a special spinning cell with a small-diameter nozzle and a high pressure (up to 10 atm) has provided the formation of hyaluronic acid-based nanofibers with a diameter of 100–300 nm.

The review presents modern advances in the synthesis of biodegradable polymers based on lactide of various topologies and also analyzes the main methods for preparation of nanoparticles that show promise for the creation of targeted drug delivery systems.

В обзоре представлены современные достижения в области синтеза биоразлагаемых полимеров на основе лактида различной топологии, а также проведен анализ основных методов получения наночастиц, перспективных для создания систем адресной доставки лекарственных препаратов.

Modern pharmaceutics are actively developing towards the design of targeted drugs. The development of selectively acting formulations requires the creation of smart delivery systems based on carriers that would first find the target cells and enter them and then release the active substance locally. Nanoparticles of biocompatible and biodegradable polymers can be effectively used as such carriers. Flexible regulation of the molecular structure and architecture of polymers, as well as the modification of nanoparticles with vector molecules, allows one to construct carrier particles for the development of nanoformulations for active agents of various nature. This review presents the main approaches to the design of nanoformulations for targeted delivery, describes the methods for the preparation and study of nanoparticles based on hydrophobic and amphiphilic biodegradable lactide polymers, and discusses the effect of the molecular structure and preparation conditions on the characteristics of nanoparticles in detail. Some results of research in this area of the Kurchatov complex of NBIСS nature-like technologies are also presented.

Nanoparticles based on biocompatible methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG(113)-b-P(D,L)LA(n)) copolymers as potential vehicles for the anticancer agent oxaliplatin were prepared by a nanoprecipitation technique. It was demonstrated that an increase in the hydrophobic PLA block length from 62 to 173 monomer units leads to an increase of the size of nanoparticles from 32 to 56 nm. Small-angle X-ray scattering studies confirmed the "core-corona" structure of mPEG(113)-b-P(D,L)LA(n) nanoparticles and oxaliplatin loading. It was suggested that hydrophilic oxaliplatin is adsorbed on the core-corona interface of the nanoparticles during the nanoprecipitation process. The oxaliplatin loading content decreased from 3.8 to 1.5% wt./wt. (with initial loading of 5% wt./wt.) with increasing PLA block length. Thus, the highest loading content of the anticancer drug oxaliplatin with its encapsulation efficiency of 76% in mPEG(113)-b-P(D,L)LA(n) nanoparticles can be achieved for block copolymer with short hydrophobic block.

Synthetic surfactants have a wide application in various areas from medicine to agriculture, with biodegradable surfactants holding the greatest promise. Promising compounds for the synthesis of such surfactants are polyethylene oxide and polymers are the poly(α-hydroxyacid)s: polylactide (i.e. PLA), polyglycolide (i.e. PGA), poly-ε-caprolactone (PCL), polyhydroxybutyrate (PHB) and their copolymers. Because the biodegradation of polymeric surfactants yields natural metabolites, their medical and biotechnological applications are most attractive. A number of studies shows advantages of branched polymer surfactants compared linear surfactants, however, systematic studies of the correlation between the branched structures of amphiphilic copolymers and their surface activities are absent. Hyperbranched polyester polyol based on 2,2-bis(methylol)propionic acid are widely used as modifiers of polymeric materials (for example, in the manufacture of paintwork materials), additives for polymers to improve extrusion and also as nanocontainers for targeted drug delivery. In the present study the colloidal chemical properties of the polyether polyol 2,2-bis (methylol) propionic acid of the fourth pseudo generation (trade name Boltorn H40) were studied and it was shown that they reduce the interfacial tension at the hydrocarbon solution of surfactant/water to low.