Naproxen encapsulated in nanostructureted lipid carries for parenteral administration: from preparation to pharmacological tests

Author(s)

Viviane Aparecida Guilherme Damasio

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2017-04-10

Examining board members

Eneida de Paula; Marlus Chorilli; Francisco Benedito Teixeira Pessine; Giovana Tofoli; Leonardo Fernandes Fraceto

• Advisor: Eneida de Paula; Cíntia Maria Saia Cereda

Abstract

The present work presents the development of a formulation capable to prolong the action of the non-steroidal anti-inflammatory drug naproxen (NPX) in an animal model. The development of nanostructured lipid carrier (CLN) formulations was based on a 24 factorial design, which variables were: the ratio between solid (cetyl palmitate) and liquid (caprylic / caprylic acid triglycerides) lipids, surfactant (Pluronic F-68) and NPX concentrations. The analyzed responses were: size, polydispersity (PDI) and Zeta potential of the nanoparticles. The formulations that presented smaller size and PDI were selected for futher physical-chemical and stability studies, in which the formulations were found stable for 12 months. The characterization of the material was carried out by differential scanning calorimetry (DSC), infra-red spectroscopy with attenuated total reflectance (FTIR-ATR) and transmission electron microscopy (TEM). Encapsulation efficiency (% EE) measurements showed that more than 99% of NPX got encapsulated in the lipid matrix; In vitro release kinetics experiments revealed a sustained release profile for encapsulated NPX. Cell viability studies using Balb-c mice fibroblasts (3T3) treated for 72-hour showed lower toxicity for encapsulated NPX in comparison to the free drug. The formulation containing 70% solid:liquid lipid ratio, 2% Pluronic F68 and 3% naproxen was selected for animal testing. Pharmacological tests performed temporomandibular joint (TMJ) inflammatory model induced by carrageenan showed the significant anti-inflammatory effect of encapsulated NPX, for more than a week, after evaluation of the number of leukocytes and levels of the proinflammatory cytokines TNF-alpha and IL -1beta. From the results it was concluded that the formulation developed showed high efficiency of encapsulation for naproxen, decreased its intrinsic toxicity, and elicited an anti-inflammatory effect for more than a week, being stable for up to 12 months of storage (AU)

• FAPESP's process: 13/10766-0 - Naproxen encapsulated in nanostructured lipid carriers for parenteral administration: preparation, characterization and pharmacological evaluation.
• Grantee: Viviane Aparecida Guilherme Damasio
• Support Opportunities: Scholarships in Brazil - Doctorate