Development of orodispersible films and mucoadhesive microparticles from pullulan-based cationic copolymers for application in controlled drug delivery systems

• Grant number: 21/11410-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): March 01, 2022
• Effective date (End): February 28, 2023
• Field of knowledge: Engineering - Biomedical Engineering
• Principal Investigator: Simone de Fátima Medeiros Sampaio
• Grantee: Layde Teixeira de Carvalho
• Supervisor: Maria Inês Ré
• Host Institution: Escola de Engenharia de Lorena (EEL). Universidade de São Paulo (USP). Lorena , SP, Brazil
• Research place: École Nationale Supérieure des Mines d'Albi-Carmaux (IMT Mines Albi), France
• Associated to the scholarship: 19/12940-4 - Biodegradable and biocompatible nanoparticles for controlled release of paclitaxel and fluorouracil for the treatment of Hepatocellular Carcinoma (HCC), BP.DR

Abstract

In the project developed at EEL-USP, the student evaluates the use of a cationic copolymer, obtained from the chemical modification of the polysaccharide pullulan (PUL). The final material has the ability to self-aggregate in aqueous media forming biodegradable nanoparticles, to study the encapsulation and release, in a controlled manner, localized and with synergistic effect, of two chemotherapeutic agents, paclitaxel (PTX) and fluorouracil (5-FU). To this point, syntheses and characterizations of pullulan modified with cationic groups (PUL-DEAE) and amphiphilic copolymers consisting of pullulan grafted with poly(L-lysine) have been performed. The hydrophobic block size was varied in the copolymers, aiming to evaluate its influence on the properties of the nanoparticles in aqueous media. Focus on the application of polymers based on pullulan for oral rout administration, the preparation of orodispersible films and mucoadhesive microparticles is, therefore, the object of interest of the present proposal for an internship abroad and was encouraged through the contact of the student and her advisor with Prof. Dr. Maria Inês Ré, professor and deputy director of the Centre Rapsodee within the IMT Mines Albi, which belongs to the renowned University of Toulouse, France and to Mines-Telecom Institut (IMT). Prof. Maria Ines is also the director of a technology platform on advanced pharmaceutical formulations to support the industry (GALA platform). During the internship abroad, new applications will be investigated for cationic pullulan, which has been considered a versatile and innovative polymer capable of being applied in different methods of actives delivery. The use of pullulan, cationic pullulan and copolymer will be explored for the development of two different structures for oral delivery of active ingredients: mucoadhesive microparticles and orodispersible films. The technologies used for the preparation of the microparticles and the films will be spray drying and hot extrusion, respectively. The main objective of the internship abroad will consist in the optimization of the process parameters for the preparation of films and microparticles with suitable properties, mainly in terms of thermal properties, water absorption capacity and disintegration time in simulated (salivary/gastrointestinal) media. Other biopolymers such as trehalose, chitosan, poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) will also be added as plasticizers to form the films. Depending on the evolution of the project's development, the encapsulation and in vitro release of an active ingredient for cancer treatment may be evaluated. In this case, the materials and process conditions that provided the best results in the previous step will be selected. The host institution, IMT Mines Albi, France, is a well-established school with acknowledged excellence in and outside of France, providing great opportunities for research development in the research field of interest of this project in its Rapsodee Centre. If the present proposal is approved, a formal cooperation agreement will be signed between the universities so that the doctorate will be conducted in the co-tutorship system, with double degrees for the student. It is important to emphasize that Dr. Maria Inês also has extensive experience in the field of microtechnology applied to processes for generating polymeric particles. This BEPE grant will greatly add to the project already developed by the student, since it will provide the materials studied a new potential application in controlled release of drugs, including the oral route of administration for cancer therapy, which is still a challenge that researchers around the world wish to overcome. In addition, it will be a very significant contribution to the student's professional and personal. (AU)