Preparo e caracterização de diferentes sistemas de liberação modificada para o anestésico local articaín

Author(s)

Nathalie Ferreira Silva de Melo

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2014-08-08

Examining board members

Leonardo Fernandes Fraceto; Marco Vinícius Chaud; Nelson Eduardo Duran Caballero; Marcelo Henrique Napimoga; Michelle Franz Montan

• Advisor: Leonardo Fernandes Fraceto

Abstract

Local anesthetics (LA) are drugs used in controlling chronic or acute pain. The articaine (ATC) is an LA of amino-amides class which have lower toxicity and higher potency than lidocaine and has been the drug of choice in dental procedures and epidural anesthesia. Desirable features for LA include pain control during clinical procedures and the reduction of local and/or systemic toxicity. Thus, an alternative that has been shown to promote these desirable effects is the placement of these drugs in modified release systems. In this regard, polymeric nanoparticles (PN), solid lipid nanoparticles (SLN) and small unilamellar liposomes (SUV) are nanocarriers systems able to promote modification of the drug release profile and have a diameter of less than 1 µM. NP is classified as nanospheres (NS), comprising a polymeric matrix and nanocapsules (NC), consisting of a polymeric shell around an oily or aqueous core. SLN are formed by a lipid matrix which appears solid at room temperature. SUV are vesicular structures composed of phospholipids bilayers which spontaneously arrange themselves in an aqueous medium. Hydrogels are polymeric networks that when dispersed in aqueous medium assume a conformation donor viscosity of the formulation. The objective of this work was to prepare and characterize different modified delivery systems for ATC (neutral and ionized form) including PN, SLN, SUV and hydrogels (containing free and encapsulated ATC) in order to improve its pharmacological properties targeting future clinical application for infiltrating and/or topically. The optimization of PN and SUV suspensions was achieved through a factorial design and analyzed the properties: mean diameter, polydispersity, zeta potential and encapsulation efficiency of the drug. All suspensions were prepared with ATC 2%. Particles were obtained with diameter between 100-400 nm and polydispersity index lower than 0.2. The encapsulation efficiency was achieved quite satisfactory (between 50 and 70%). The physico-chemical properties of the suspensions were assessed as function of time in order to determine the stability of the particles. The selected formulations showed no significant changes of these properties, being considered stable for a period of 120 days of storage at room temperature. In vitro release experiments showed slower release of ATC when encapsulated in PN, SLN and SUV, in relation to the free ATC. In vitro cytotoxicity tests on 3T3 and CHO cells revealed that the free ATC induces cell death concentration-dependent, an effect which was partially reversed by ATC in the encapsulation in PN, SLN and SUV, indicating low toxicity of the proposed formulations. The hydrogels containing free and encapsulated ATC showed good consistency, uniformity and stability. In the rheological tests, the gels exhibited pseudoplastic behavior with tixotropy, which can improve the effectiveness of the drug. The gel containing the NC-PCL with ATC showed faster onset of permeation and slower release (up to 8 hours). The results showed that it was possible to prepare hydrogels and nanocarriers for ATC, with good results in modification of drug release and decreased cytotoxicity profile, being a future alternative for pain control (AU)

• FAPESP's process: 10/18529-0 - Modified release systems for local anesthetic articaine aim to odontological applications
• Grantee: Nathalie Ferreira Silva de Melo
• Support Opportunities: Scholarships in Brazil - Doctorate