Development of nanostructured lipid carriers functionalized with hyaluronic acid for local anesthetics modified release by intra-articular route

• Grant number: 15/26189-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): March 01, 2016
• Effective date (End): July 23, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Daniele Ribeiro de Araujo
• Grantee: Renato Grillo
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics, AP.TEM

Abstract

The management of post-operative pain influences the patient compliance in orthopedic surgical procedures, such as arthroplasty. Systemic administration of opioids has been used for pain relief, but is associated to side effects, including nausea, dizziness, vomiting, urinary retention, pruritus, and bradypnea sedation, which can slow rehabilitation and increase the patient stay in the hospital. Then, as an alternative to reduce the use of systemic opioids, local anesthetics (LA), such as bupivacaine (BVC) and ropivacaine (RVC) are being administered directly at the site of surgical trauma, producing good analgesia without impairing motor function. However, LA present short residence time in the joint and thus is required the administration of multiple doses or the use of catheters with an infusion pump for prolonging the drug effect. Nevertheless, the use of infusion pumps are associated with increased risk of infection and tissue necrosis. Thus, new strategies to prolong the effect of LA, such as the development of drug carriers, have been proposed. However, the drug carriers should have similar characteristics to those of synovial region. In this sense, the purpose of this project involves the development of a modified delivery system composed of nanostructured lipid carriers (NLC) functionalized with hyaluronic acid (main polysaccharide present in the synovial liquid) for local anesthetics, such as bupivacaine (BVC) or ropivacaine (RVC), for administration by intraarticular route (IA). This proposal involves three steps: the preparation and physicochemical characterization of functionalized nanocarriers, the drug release kinetics evaluation and the assessment of in vitro cytotoxicity of this system. The significance of this lies in the development of new pharmaceutical formulations for local anesthetics, looking forward the control of postoperative pain, with high drug-nanocarrier association, greater stability, long duration of action and lower toxicity. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GRILLO, RENATO; DIAS, V, FABIANA; QUEROBINO, SAMYR M.; ALBERTO-SILVA, CARLOS; FRACETO, LEONARDO F.; DE PAULA, ENEIDA; DE ARAUJOL, DANIELE R.. Influence of hybrid polymeric nanoparticle/thermosensitive hydrogels systems on formulation tracking and in vitro artificial membrane permeation: A promising system for skin drug-delivery. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 174, p. 56-62, FEB 1 2019. (15/26189-8, 14/14457-5)