Projects / Programmes
Novi dendritski polimeri kot nosilci za kontrolirano dostavo zdravilnih učinkovin (Slovene)
| Code |
Science |
Field |
Subfield |
| 2.04.03 |
Engineering sciences and technologies |
Materials science and technology |
Polymer materials |
| Code |
Science |
Field |
| 2.05 |
Engineering and Technology |
Materials engineering |
Researchers (11)
Organisations (2)
Significance for science
The results of this research project are important for the development of fundamental and applied knowledge in an extremely interesting and rapidly evolving field of dendritic polymers as well as for the use of dendritic polymers in modern biomedical and pharmaceutical applications. The topic of dendritic polymers for drug delivery application is one of the hottest areas in the development of new drug delivery systems since a number of pharmaceutical active ingredients require carriers that are able to improve drug solubility, bioavailability, protect the drug from premature degradation or lengthen the period of optimal therapeutic drug concentration in the body. In this way, a greater impact of drug treatment can be achieved with reduced amount and frequency of drug administration at the same time. In addition, more targeted drug delivery with lower toxicity and unwanted side effects is possible to acchieve.
The topic of biodegradable and biocompatible dendritic polymers for the use in biomedical application fits among the state-of-the art areas in polymer science as indicates an intensive growth of scientific publications in the field of dendritic polymers. Dendrimers and other forms of dendritic polymers (hyperbranched polymers, dendrizones, lineardendritic hybrids, etc.) represent the most promising direction in the development of polymers in which attempts are made to use natural building blocks and control the complex polymer molecular architecture in order to achieve biocompatibility and in particular accurate and often exceptional functionality, respectively. After all these criteria, synthetic polymer science seeks to replicate the natural structures by means of complete control over molecular and supramolecular structure of biological compounds to attain well defined functionality, while avoiding the toxic effects.
The results of this project revealed that neutral dendritic structures with hydroxyl functional groups are nontoxic and, therefore, most suitable as carriers for low molar mass drugs. The dendritic structures showed higher loading capacity than conventional neutral polymers with linear architecture. Besides, the loading capacity depends on the type of terminal functional groups and molecular weight or generation of dendrimer. Solid dispersions based on dendritic polymers significantly improve the water-solubility of highly insoluble drugs. Due to extremely high higroscopicity of solid dispersions, we prepared a final dosage form, i.e., the film-coated tablets, which are applicable for oral drug administration. The knowledge acquired during the project duration enables better understanding of the relationship between structure of active ingredient/dendritic polymer complexes and mechanisms of improving the solubility of poorly-soluble active substances when they are within solid dispersions based on dendritic polymers.
The research comprising the improvement of water-solubility and dissolution rate of poorly soluble active substances by the preparation of solid dispersions based on dendritic polymers represent an original scientific contribution and unique approach to optimize drug administration and to achieve the desired therapeutic effect. Research and results of this project allows better understanding of the structure of solid dispersions and mechanisms of improving the solubility of poorly-soluble active substances by preparing solid dispersions based on dendritic polymers. Only in this way the experimental findings can be implemented in practice for development of drug formulation in pharmaceutical industry.
Significance for the country
The research on the synthesis of dendritic polymers in Slovenia is new, whereas worldwide the topic is interesting already for about 50 years; in recent years with great intensity since the dendritic polymers have peculiar properties as compared to linear polymers. For this reason, dendritic polymers have become very interesting structures also from the application point of view. Since dendrimers have exactly defined structure and molar mass, but, on the other hand, their synthesis is complex and time consuming, they are particularly attractive for application in hightech fields, i.e., biomedical and pharmaceutical fields for drug delivery application.
The results of this project are defined synthetic procedures for the preparation of dendrimers of different generations with new chemical composition, well defined structure and molar mass. Our studies have contributed significantly to acquisition of new scientific knowledge on the synthesis and isolation of dendritic structures as well as on characterization and application of dendritic structures for drug delivery purposes. We defined also the biocompatibility of polyesteramide dendritic structures and optimized the procedure for non-covalent loading of active substances on/in the dendritic structures. The research aimed at improving poor water-solubility of low molecular weight active substances showed that the preparation of solid dispersions based on dendritic polymers can significantly improve water-solubility and thus bioavailability of active ingredients. We found that loading capacity of dendritic polymers depends on the intrinsic characteristics of the polymeric carrier and the active substance. Within the project we developed a prototype of the final dosage form for the oral delivery of highly insoluble antidiabetic drug glemepiride by preparation of solid dispersion based on dendritic polymers and integration of solid dispersions into the film-coated tablets.
The acquired knowledge on the role of polymeric carriers in drug delivery was spread in the project team of experts and especially to cooperating students who are able to use the important practical and theoretical experiences further and thus multiplying the benefits of the project over a longer period. The involvement of respected research groups from abroad enables a contact with the most ambitious and advanced scientific achievements in the world and has a positive impact on the recognition of the Slovenian science outside Slovenia.
Most important scientific results
Annual report
2010,
2011,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
