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Pharmacological studies of advanced surgical devices based on Layered Double Hydroxides polymer composites

Grant number: 18/22782-4
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): January 03, 2020
Effective date (End): July 02, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Vera Regina Leopoldo Constantino
Grantee:Mariana Pires Figueiredo
Supervisor abroad: Cesar Viseras Iborra
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Universidad de Granada (UGR), Spain  
Associated to the scholarship:16/13862-9 - Conception and development of drug nanocarriers based on layered double hydroxides, BP.DD

Abstract

Iron-based Layer Double Hydroxides (LDHs) are materials greatly studied in the field of drug delivery systems. LDHs are interesting matrices to constitute polymer surgical devices, such as suture wires and implantable films or dressings, due to the possibility to improve polymers mechanical properties, to assist tissues recovering andtoperform a prolonged release ofbioactive anions,such as antimicrobial and analgesic species, avoiding post-surgical infections and conferring a faster, painless and high-quality wound healing. The first step of the FapespPhD project, entitledConception and Development of Drug Nanocarriers Based on Layered Double Hydroxides (2016/13862-9), is concerned with the obtainment of LDHs with composition Mg2Fe1-xAlx and Zn2Fe1-xAlx (with x equal to 0, 0.25, 0.50, 0,75 and 1), intercalated with Cl- (control), naproxenate(NAP) and abietate (ABI) anions.The materials were already prepared and the characterization showed that LDHs phases were obtained and were able to encapsulate satisfactory amounts of the organic anions.In the second step, the most promising compositions were chosen to the development ofcompositesin form of films,obtained by casting, whose polymers(PLGA and PEBA) biocompatibility were attested through in vivo intramuscular implantation in rats.Polymer films containing NAP and ABI salts and composites formed with Mg2Fe0.5Al0.5 and Zn2Fe0.5Al0.5 LDHs, intercalated with Cl , NAP and ABI are being characterized. The materials present good resistance to handling. All films containing Mg-LDHs are visually homogeneous. These results encouraged the advancement of research with iron-based LDHs and polymer composites. For this purpose, it is intended to split the internship total duration granted by BEPE program in two abroad experiences of six months each. The first internship, to be carried out in France (FAPESP process 2018/22726-7), aims the preparation and characterization of two types of advanced polymer surgical devices prepared by electrospinning methods: suture wires and implantable films or dressings, able to promote a prolonged release of NAP and ABI species intercalated into iron-based LDHs. The carriers will be designed to prevent surgical site infection combined with anti-inflammatory activity, by the release of ABI, whose performance will be evaluated by comparison with the devices presenting LDHs intercalated with NAP. It will also be evaluated the synergic effect of the presence of both LDHs, intercalated with NAP and ABI anions, in the composites.The second internship, subject of this project, intends to advance the research of the surgical devices developed and characterized in Brazil and possibly in France through the evaluation of the material's pharmacological performance. In vitro drug dissolution applying Franz cell devices will be employed. Cell cultures simulating the local of administration of the devices will be applied for cytotoxicity, proliferation and migration/proliferation tests in order to study the properties of the materials to improve wound healing.