The 5th stage of the Project (October- December 2011) completed
The 5th stage of the mega project “Biotechnology of new materials” (October-December 2011) within the framework of the Agreement No. 11. G34.31.0013 between the Ministry of Education and Science of the Russian Federation, Siberian Federal University and the leading scientist under the supervision of the leading scientist Prof. Anthony John Sinskey was completed.
In the period from October 1 till December 31, 2011 in full compliance with the research schedule research, educational and organization works were completed.
The following results were obtained:
Using polymer matrices in the form of microparticles constructed at Stages 1/2 from highly purified samples of biodegradable polymers (PHAs) of various composition synthesized and characterized at Stage 1, the method of constructing polymer microparticles loaded with drugs was developed; the family of experimental samples of polymer microparticles of various diameters loaded with various drugs was obtained. We developed the method of applying the drug form of microparticles for local introduction into the organism; the drug efficiency of microparticles loaded with DOX was proved in the experiment with laboratory mice with the solid variant of Ehrlich’s carcinoma. For the first time it was proved that the experimental form of doxorubicin deposited in microparticles from the resorbed polymer “Bioplastostan” can be applied locally in the zone of the tumour formation. The inhibiting effect of the experimental form of the drug is comparable in effect with the free form of doxorubicin injected daily intravenously, but unlike the latter without the negative effect on the blood system.
At the Figure: morphological structure of the tumour tissue in the place of introduction of microparticles loaded with cytostatic drug: 1 – first experimental group (one cycle dose), 2 – second experimental group (two cycle doses); а, б, в – first, second and third weeks of treatment; мч – microparticles, н – necrosis, м – muscle. Magnification х 400
Film matrices from highly purified samples of PHAs of various chemical composition were studied in a 6-month experiment at subcutaneous implantation to laboratory animals; there was no negative response to implantation from the blood of the animals and local response of the tissues, which is typical to various types of PHAs, is characterized by a short-term posttraumatic inflammation without formation of fibrous capsules. In the chronological 6-month experiment for the first time the effects of the subcutaneous implantation of PHA matrices of various chemical composition were studied. It was demonstrated that the response of the tissues is the same and is characterized by a short-term posttraumatic inflammation without formation of fibrous capsules and does not have other negative effects.
At the Figure: tissue response to the subcutaneous implantation of 2D matrices produced from degradable polymers of various chemical composition to the laboratory mice. 180 days after implantation. Stained with hematoxylin-eosin. Marker 40 microns
It was determined that activity of PHA biodegradation in vivo increases in the line P3HB – P3HB/3HV – P3HB/4HB – P3HB/3HH; macrophages and foreign-body giant cells actively participate in this process. With implementation of highly efficient liquid chromatography it was shown that the greatest changes in the molecular weight and polydispersity of PHAs was registered for quickly degrading copolymers of P3HB/4HB and P3HB/3HH, for which expressed giant-cell tissue response of the tissues is typical at early stages.
Fig. Changes in the weight of polymer matrices during 180-day subcutaneous implantation
Biological safety of the matrices produced from all studied types of PHAs was proved, as well as the fact that they meet the requirements to the materials and devices of biomedical application.
The monograph “Degradable biopolymers: production, properties, application” was published
2 project team members successfully defended their Ph.D. theses:
E.S. Vasilenya. Experimental basis for application of new PHA-based suture material (Ph.D. in Medicine, specialization 14.01.17 – surgery)
E.D. Nikolayeva. Properties of resorbing matrices produced from polyhydroxyalkanoates of various chemical composition (Ph.D. in Biology, specialization 03.01.060- Biotechnology).