Preparation of microneedles based on hyaluronic acid incorporating nanostructured lipid carriers containing resveratrol

• Grant number: 17/03496-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): June 26, 2017
• Effective date (End): July 28, 2017
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Maria Helena Andrade Santana
• Grantee: Andréa Arruda Martins Shimojo
• Supervisor: Eliana Maria Barbosa Souto
• Host Institution: Faculdade de Engenharia Química (FEQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Universidade de Coimbra (UC), Portugal
• Associated to the scholarship: 14/27200-2 - Association studies of platelet-rich plasma with acid hyaluronic scaffolds for applications in regenerative medicine, BP.PD

Abstract

The incidence of age-related diseases is increasing and seriously affecting millions of people around the world. Even with the progress of regenerative medicine, current therapies still have numerous limitations. Thus, there is an increasing search for innovative technologies and cost-effective approaches that focus primarily on patient comfort. In this context, products based on hyaluronic acid (HA) have played a fundamental role and are mainly used as systems for the encapsulation and controlled release of bioactives, such as scaffolds for cell proliferation and differentiation, as a viscoelastic component for the treatment of degenerative diseases of joints or for dermal filler, and as promoters of wound healing. The functions and applications of HA in regenerative medicine are basically associated with its favorable biological properties, structural characteristics, and possible chemical modifications of the polymer, which determine its rheological properties, solubility, hydration and specific cellular recognition. On the other hand, the effects of natural antioxidant and anti-inflammatory resveratrol (RESV) have also been evaluated in the treatment of degenerative and aging-related diseases. RESV is a polyphenolic compound found in grapes, berries and peanuts that has been shown to block the activation of nuclear factor ºB (NF-ºB) reducing the generation of reactive oxygen species (ROS) and proinflammatory cytokines. However, despite the beneficial therapeutic effects, HA and RESV present a number of limitations, including poor in vivo stability, rapid metabolism and poor mechanical properties, restricting their applications. In recent years, needles with micrometric dimensions have been shown to be effective in the transdermal administration of different drugs, ranging from small molecules to macromolecules, nanoparticles and fluid extracts. Microneedles have the advantage of perforating the outermost layer of the skin (stratum corneum) non-invasively and painlessly, significantly increasing the rate of transdermal drug permeation. Additionally, biocompatible and biodegradable polymers, such as HA, have become promising for microneedle manufacturing mainly due to its biocompatibility, safety, solubility and swelling properties, manufacturing ease and reproducibility, and possibility of process scale-up. However, hydrophobic compounds, such as RESV, present serious limitations in their incorporation into microneedles of hydrophilic polymers such as HA. Thus, in this project, HA microneedles containing RESV incorporated in the form of nanostructured lipid carriers (NLC) or covalently conjugated to HA, will be prepared. The presentation of HA in the form of microneedles will represent an innovative and minimally invasive form for transdermal administration of active principles, which may bring benefits associated with tissue repair. The covalent conjugation with RESV will improve the mechanical properties of the microneedles, whereas the incorporation of the NLC will allow the incorporation and modified release of the RESV. The development of this project will open promising perspectives in the context of regenerative medicine and in a broad spectrum of other applications.