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Pectin-Containing Composite Materials

#KR-1880


Fabrication of Pectin-Based Composite Materials for Biomedical Application

Tech Area / Field

  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • CHE-POL/Polymer Chemistry/Chemistry
  • MED-OTH/Other/Medicine

Status
8 Project completed

Registration date
01.09.2010

Completion date
17.03.2014

Senior Project Manager
Savinova N V

Leading Institute
National Academy of Sciences of Kyrgyzstan / Institute of Chemistry and Chemical Technology, Kyrgyzstan, Bishkek

Collaborators

  • Global Institute for Bioexploration, USA, NJ, New Brunswick

Project summary

The goal of the present project is to fabricate composite nanomaterials (possibly metal-containing) based on natural biological polymers (pectin substances) to be ultimately applied as antitumor and chemosensitizing substances. This project is therefore in the field of the design of bionanomaterials and nanobiomaterials that are to be used as substances for biological and pharmaceutical preparations. Namely, incorporation of natural (biological) materials into nanocomposites (bionanomaterials) and the application of nonbiological nanomaterials in medicine (nanobiomaterials). Biological natural polymers as pharmaceutical substances and drug carriers have many advantages, including good biocompatibility, nontoxicity, and adjustable controlled release properties.

Pectins have a wide spectrum of physiological activity, including immunomodulating and gastroprotective action. A property of great importance is the anticarcinogenic and/or antimetastatic effects of pectins. It has been shown that pectins with different esterification degrees induce the apoptosis of adenocarcinoma of the human large intestine. It is proposed that pectin polysaccharides bind proteins on the surface of cancer cells responsible for the adhesion of tumor cells to healthy tissues. There are reports concerning the physiological activities of pectins on the interactions between fibroplast growth factors and receptors, on the modulation of lung colonization of B16-F1 melanoma cell (Platt, 1992) and on the inhibition of human cancer cell growth and metastasis in nude mice. Pectin diets could also reduce the incidence of colon cancer in rats (Nangia-Makker, 2002). It was found the influence of pectin derivatives on enzymes activity. Such inhibitory effect of pectin hydroxamic acid on the activities of semicarbazide-sensitive amine oxidase (SSAO) and angiotensin converting enzyme was revealed. There are several classes of pharmacological agents that have been used in the treatment of hypertension (Mark, 2000). One class of antihypertensive drugs known as angiotensin I converting enzyme (ACE) inhibitors (ACEI) has a low incidence of adverse side effects and are the preferred class of antihypertensive agents for the treatment of patients with concurrent secondary diseases (Fotherby, 1999). Several endogenous peptides such as enkephalins, ß-endophin, and substance P were reported to be competitive substrates and inhibitors AEE (Mullally, 1996). Several antioxidant peptides (reduced glutathione and carnosine-related peptides) also exhibited ACEI activities. SSAO activity was implicated to have roles in atherosclerosis, endothelial damage, and glucose transport into adipocytes).

A variety of pharmacological properties of pectins suggest them as a potential source of new drugs. The majority of antiblastic drugs produce toxic effect on actively regenerating cell systems, which limits their effective use. Therefore, the search for new means increasing selective effect of cytostatics is a pressing problem in tumor chemotherapy. Vitality of these research especially for Kyrgyzstan is obvious because of during the Soviet period, discharges of radioactive elements resulting from uranium mining industry in the environment were a common practice and, as a result, more than 80 contaminated sites are accounted for in the Republic. Although uranium processing is no longer practiced in Kyrgyzstan, a large number of open landfills and uranium ore storages still remain abandoned at the vicinity of these settlements. Unfavourable state of the environment nearby uranium fields in Kyrgyzstan negatively impacts health of especially women and children. An aggravation comes from traditional food such as milk and meet of livestock bred nearby those dumps and fills. According Ministry of Health, there are no children in good health in settlements nearby uranium fields. Most of them simultaneously have various chronic illnesses along with delay in physical, physiological and sexual development. There is a trend of high infant morbidity and mortality, especially cancer mortality.

The basis of the development under this project proposal is previous studies of the project participants, in particular, concerning methods of synthesis and testing of the metal-polymer nano-composites, including the metalocomplexes based on pectin substances (Jorobekova, 1986; Jorobekova, Kydralieva, 1998 Aimukhamedova et al., 1998, 1999, 2002- 2004; Pomogailo A.D., Dzhardimalieva G.I., et al., 2000-2009). According to the results obtained pectin substances have a wide spectrum of physiological activity. At the same time, higher biological ability as antimicrobial, anticancer, and chemosensitizing agents was observed for complexes of pectin substances with biocompatible metals. It has been demonstrated that the pectin metalocomplexes possessed equal or higher antitumor potential in relation to sarcoma 45, Pliss lymphosarcoma, and Ehrlich’s tumor. Tumor growth inhibition was 63-75%. It was also established that some of metalocomplexes of pectin substances were capable of enhancing the antitumor effect of certain cytostatic agents while decreasing their toxic and side effects. Modified pectin complexes enhanced the antitumor activity of cytostatic agents achieving tumor growth inhibition of 71-96% and decreasing the toxic effect of chemical medicines on the tumor carriers by such indicators as the animals mortality, general condition, and intoxication symptoms. The combination of metal-derivatized pectins with known antitumor agents (5-fluorouracil, cisplatin) surpasses the activity of the latter given by separate injection. The weight of tumors in animals with transplantable tumors - sarcoma 45, Pliss lymphosarcoma, Ehrlich’s tumor - was several times smaller in comparison with those under control treatment using cytostatic agents. All the experiments confirmed not only high antitumor potential of pectin materials but also their adjuvant potential to cancer therapy to prevent metastasis.

In order to reach the goal it is necessary to solve the following tasks:

  1. Isolation of pectin from the beet roots and leaves (Beta vulgaris) and determination of the structure of the isolated pectin,
  2. Determination in detail the relevant bioactive part of the isolated pectin;
  3. Fabrication of nanocomposites based on pectin and nanoparticles of metals;
  4. Characteristization of the structure and physicochemical properties of nanocomposites by elementary and molecular-mass distribution, granulometric composition, porosity, size of particles and by their distribution;
  5. Estimation of the anticancer and chemosensitizing potential of the nanocomposites;
  6. Evaluation of possible toxic properties of the nanocomposites;
  7. Scale-up of technology for preparating effective nanoscale pectin derivatives

Publications relevant to the project are listed below:
  1. Pomogailo A.D., Rozenberg А.S., Uflyand I.E. 2000: Nanoparticles of metals in polymers, М.: Chemistry, 2000, 672 p.
  2. Pomogailo A.D., Kestelman V.N. 2005: Metallopolymer nanocomposites. Springer, Heidelberg, 563 p.
  3. Pomogailo A.D. 2006: Metallopolymer Nanocomposites. Macromolecular metallocomplexes as precursors for polymer, polymer-inorganic and bionanocomposites. Chapter in book “Metal and Metalloid Containing Macromolecules”, ed. by Ch. Carraher, Jr., C. Pittman, Jr., Abd-El-Aziz, M. Zeldin, and J. Sheats, Wiley-Interscience, John Wiley and Sons, Inc., New York, 2006, 7. Chapter 4. 87-220.
  4. Pomogailo A.D., Rozenberg A.S., Dzhardimalieva G.I. 2006: Controlled pyrolysis of metal-containing precursors as a way for syntheses of metallopolymer nanocomposites. Chapter in Book: “Metal-Polymer nanocomposites” (Eds. L. Nicolais, G. Carotenuto), Wiley, 2006, 75-122.
  5. Pomogailo A.D., Kestelman V.N. 2005: Nanobiocomposites. Chapter 9 in book “Metallopolymer nanocomposites”, Springer, 2005, 337-422
  6. Ashubaeva, S.D., Kozlova I.I. 1991: Metalcomplex derivatives of pectins and their use. Bishkek, Ilim, 94 pp.
    Aimukhamedova, G.B., Aliyev D.E., Shelukhina N.P. 1984: Properties and application of pectin sorbents. Frunze, Ilim, 116 pp.
  7. Aimukhamedova G.B, et al. 1999: Potassium polygalacturonate with chemiosensitizing tumor effect. Kyrgyz prepatent, 318.
  8. Ushbaeva, G.G, et al. 2002: Availability of plant-based biopolymers for tumor corrective therapy. In: Materials Int. Conf. "Safety and life quality in big city". Almaty, 134-138.
  9. Aimukhamedova G.B, et al. 2003: Metalcomplexes of piroglutamin acid and polygalacturon as new anticancer compounds with a wide range of physiological and therapeutic effects. Journal of Kyrgyz National University, 3(1), 106-112.
  10. Aimukhamedova G.B., et al. 2004: Ni polygalacturonate with chemisensitizing tumor effect. Kyrgyz Patent, 712.
    Aimukhamedova, G.B., et al.
    2004: Co polygalakturonate with chemisensitizing tumor effect. Kyrgyz Patent, 734.

Fields of application and perspectives of commercialization.

New systems containing polymeric materials and nanometals for application in medicine as substances for anticancer and chemosensitizing tumor drugs will be developed. Results and approaches of the project could be of interest for the leading producers of commercial anticancer drugs.


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