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Membranes for Transdermal Drug Delivery

#2892


Development of Artificial Membranes to be Used in Medicine and Human Ecology Based on the Imitation of Drug Transdermal Delivery Processes

Tech Area / Field

  • MAT-SYN/Materials Synthesis and Processing/Materials
  • BIO-OTH/Other/Biotechnology
  • MED-DRG/Drug Discovery/Medicine
  • ENV-EHS/Environmental Health and Safety/Environment

Status
3 Approved without Funding

Registration date
22.09.2003

Leading Institute
Lomonosov Academy of Fine Chemical Technologies, Russia, Moscow

Supporting institutes

  • A.V. Topchiev Institute of Petrochemical Synthesis, Russia, Moscow\nScientific Research Institute of Chemistry and Technology of Organo-Element Compounds, Russia, Moscow\nState Scientific Research Institute of Medical Polymers, Russia, Moscow

Collaborators

  • Institute of Technology, Ireland, Sligo\nMedennium Inc., USA, CA, Irvine\nUniversity of Greenwich, UK, London\nVirginia Commonwealth University / High Technology Materials Center, USA, VA, Richmond

Project summary

The Project is aimed at creating artificial membranes to be used in medicine and human ecology, based on the imitation of processes of transdermal delivery of drugs.

Polymer systems of drug delivery to the human organism through skin at a controlled rate have been the focus of attention of the researchers worldwide for 10-15 years because they ensure:


- a quicker drug arrival at the required location (target) in the human organism, omitting the digestive system;
- increase of treatment efficiency and reduction of side (toxic) effects, caused by the introduction of a drug;
- extension of pharmacological effect duration, required by a specific treatment process;
- possibility of fast cessation of drug-involving treatment;

Prediction of risk, associated with human poisoning by toxic agents coming through skin, is also very topical.

The problem is complicated by the absence of technical approaches, allowing one to predict the rate of a chemical substance entry to the blood circulation system through skin, using simple “in vitro” experiments. Therefore the development of artificial polymer materials and membranes on their base, imitating the properties of human skin and the processes of transdermic drug delivery and toxin removal is quite an urgent task both from theoretic and applied point of view.

The present proposal fully complies with the ISTC objectives and its Statute, since it contributes to the conversion processes, providing support to “weapons” scientists in their peaceful applied research and development in the area of environmental safety and human health.

The authors believe, that currently the problem identified can only be solved using polycarbonate polysiloxane block co-polymers of a new generation, comprising a deterministic number of organosiloxane and polycarbonate units.

Although the CARBOSYL membrane, previously developed by the authors, represents a unique synthetic material, realizing a single diffusion and transportation mechanism (in combination with the human skin epidermis), the urgent need in the creation of novel modified membranes is defined by the fact, that the CARBOSYL membrane does not allow one to solve the variety of the existing technical problems, associated with the development of transdermic drug delivery systems, applied in practical medicine and human ecology. In particular, in terms of its chemical composition such a reference membrane is not a human skin analog and cannot replace the latter in the medical practice.

The project results will ensure the further development of the previous research (conducted by the authors) as applied to the technique of producing new materials, such as, modified artificial membranes to be used in medicine and human ecology, based on the imitation of the processes of transdermic delivery of drugs and exogenous toxins.

Implementation of the project objective will be provided by a joint science and methodical team of highly skilled researchers from four leading Russian institutions, including the Moscow State Academy of Fine Chemical Technology named after Lomonosov (MIFCT); Institute of Petrochemical Synthesis named after acad. A.V. Topchiev (IPS RAS); State Scientific Center “State Research Institute of Chemistry and Technology of Organoelement Compounds” (GosNIIKhTEOS); State Research Institute of Medical Polymers (IMP), which have gained a considerable experience of joint activities within the framework of ISTC science and technology cooperation in the related areas (chemical technology, medicine and biology) and possess original methods and technical approaches to synthesis and processing of new materials for the creation of novel specific targeted drug delivery means.

The scientific novelty of the expected results is associated with pioneered efforts to develop polymer materials and membranes on their base, imitating the human skin properties, characterized by high functional physico-chemical and operation parameters (diffusion, adhesion and deformation).

Application of CARBOSYL membrane as a prototype permeability barrier will ensure a more profound understanding of molecular mechanism of transdermic toxin and drug delivery.

Methods to synthesize previously unknown polyorganosiloxanes with different content and length of the siloxane unit, representing source compounds in the membrane production process, will be suggested. Modification and study of compatibility and properties of polyorganosiloxanes, containing hydrophilic polymers, will be provided. Characterization of physicochemical and operational properties of the synthesized monomers, oligomers, polymers and membranes will be performed; the delivery properties of the membranes produced will be defined using prototype systems as applied to selected drugs and exogenous toxins. All the above will ensure the improvement of methods to assess the possibility of developing transdermic delivery and intoxication risk prediction systems.

Following the project completion the results obtained are supposed to be used in the development of high-technology commercially valuable production of skin-imitating drug delivery membranes, which will be based on synthetic polymer materials.

To solve the suggested system task it is planned to conduct large-scale research and test the research results under pre-clinical and production conditions, paying attention to the following aspects:

- development of technique to synthesize new polyorganosiloxanes (source compounds in the membrane production process); definition of physicochemical and operational parameters of the synthesized compounds and materials;

- development of methods to produce and apply the membranes for transdermic delivery of drugs (domestic and foreign) and for solving human ecology problems;

- build-up of pilot batches of membranes for testing. Preparation of laboratory technological schedules for compounds, ensuring the production of the best quality membrane materials;

- investigation into technical and functional medical properties using prototypes; issue of recommendations for pre-clinical use of the membranes produced;

- pre-clinical trials of membranes with regard to laboratory testing results obtained.

The results of the work may represent a certain interest for the foreign collaborators, which have given their consent to cooperate with the project participants and are interested in providing methodical recommendations in matters, related to the membrane quality assessment and estimation of their potential use in medicine and bioecology.

To provide information support of the risk assessment process, as applied to the use of new generation membranes at all functional stages, namely, within the following chain: synthesis study of physico-chemical and operational properties assessment of medico-biological and bioecological effects of the project result application, it is first planned to apply a system (comprehensive) approach.

The project methodology covers high-technology synthesis methods and project object analysis techniques, being developed by the authors.

The project implementation will imply the use of expensive and high efficiency research equipment, previously provided to the developers by the ISTC within the framework of Projects ## 498 and 1891 (chromatography complex “SHIMADZU”, equipment and devices to be used for synthesis and study of the developed products and materials, including BUCHI Flawill Products rotational vacuum evaporators (Switzerland), mod. ROTOVAPOR R-200; rheoviscosimeter; tensometer TD-1; BUCHI melting and boiling point analyzer etc.).

The quoted references:

1. Kirilin A.D. «M.V. Lomonosov Moscow State Academy of Fine Chemical Technology». 12 November 2001, Milano, Italy, FAST, P.le Morandi, 2-Milano, #10.

2. Kopylov V.M., Zheneva M.V., Kovyazin V.A., Isaev Yu.V. Derivatives of Siliconorganic Phenols // 4-th International Symposium on Chemistry and Using of P-, S- and Si-organic compounds. St.-Petersburg, 2002, 26-31 May, L-147.

3. Pobedimsky D.G., Evgenyev M.I., Kirilin A.D., Vrublevsky E.M. Development of an Environmental Monitoring System for Nitrogen Organic Compounds (Hydrazine, Its Derivatives and Aromatic Amines) in Air, Using Sensors and Other Sensitive Elements // Russian Chemical Journal. Journal of Mendeleev Russian Chemical Society, 45 (2001) #5-6, pp. 86-92.

4. Khananashvili L.M., Kopylov V.M., Murachvili D.U. and so-work. Carbo-Functional Oligoorganosiloxanes – Modifiers for Polymeric Materials //Russian Polymer News. 3 (1998) N1, pp. 7-11.

5. L.F. Sterina, V.M. Kopylov, I.M. Raygorodsky, V.A. Kovyazin, D.G. Pobedimsky. Membrane materials on the basis of organosilicone polymers for separation of fluids mixtures by pervaporation// Membranes. Critical Technologies. 2002, #13, P. 18-32.

6. Feldstein M.M., Raigorodsky I.M., Iordansky A.L., J.Hadgraft. Modeling of percutaneous drug transport «in vitro» using skin-imitating Carbosil membrane // Journal of Controlled Release. 52 (1998), pp. 25-40.

7. . Bairamov L.F., Chalykh A.E., Feldstein M.M., Siegel R.A., Plate N.A. Dissolution and mutual diffusion of poly(N-vinil pyrrolidone) in short chain poly(ethylene glycol) as observed by optical wedge microinterferometry // J. Appl. Polym. Sci. 85 (2002), pp.1128-1136.

8. Bairamov L.F., Chalykh A.E., Feldstein M.M., Siegel R.A. Impact of Molecular Weight on Miscibility and Interdiffusion between Poly(N-vinil pyrrolidone) and Poly(ethylene glycol) // Macromol. Chem. Phys. 203 (2002) N 18, 2674-2685.


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