A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers

Author(s):Show less -

Castro, Simone R. ^[1] ; Ribeiro, Ligia N. M. ^{[1, 2]} ; Breitkreitz, Marcia C. ^[3] ; Guilherme, Viviane A. ^[1] ; Rodrigues da Silva, Gustavo H. ^[1] ; Mitsutake, Hery ^[3] ; Alcantara, Ana C. S. ^[4] ; Yokaichiya, Fabiano ^[5] ; Franco, Margareth K. K. D. ^[6] ; Clemens, Daniel ^[5] ; Kent, Ben ^[5] ; Lancellotti, Marcelo ^[7] ; de Araujo, Daniele R. ^[8] ; de Paula, Eneida ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, UNICAMP, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

^[2] Univ Fed Uberlandia, Inst Biotechnol, Uberlandia, MG - Brazil

^[3] Univ Estadual Campinas, Dept Analyt Chem, Inst Chem, Campinas, SP - Brazil

^[4] Univ Fed Maranhao, Dept Chem, Sao Luis, Maranhao - Brazil

^[5] Helmholtz Zentrum, Dept Quantum Phenomena Novel Mat, Berlin - Germany

^[6] IPEN CNEN SP, Nucl & Energy Res Inst, Sao Paulo - Brazil

^[7] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP - Brazil

^[8] Fed Univ ABC UFABC, Human & Nat Sci Ctr, Santo Andre, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 NOV 2 2021.
• Web of Science Citations: 0

Abstract

Tetracaine (TTC) is a local anesthetic broadly used for topical and spinal blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid carriers (NLC) may prolong TTC delivery at the site of injection, reducing such toxicity. This work reports the development of NLC loading 4% TTC. Structural properties and encapsulation efficiency (%EE > 63%) guided the selection of three pre-formulations of different lipid composition, through a 2(3) factorial design of experiments (DOE). DLS and TEM analyses revealed average sizes (193-220 nm), polydispersity (< 0.2), zeta potential |- 21.8 to - 30.1 mV| and spherical shape of the nanoparticles, while FTIR-ATR, NTA, DSC, XRD and SANS provided details on their structure and physicochemical stability over time. Interestingly, one optimized pre-formulation (CP-TRANS/TTC) showed phase-separation after 4 months, as predicted by Raman imaging that detected lack of miscibility between its solid (cetyl palmitate) and liquid (Transcutol) lipids. SANS analyses identified lamellar arrangements inside such nanoparticles, the thickness of the lamellae been decreased by TTC. As a result of this combined approach (DOE and biophysical techniques) two optimized pre-formulations were rationally selected, both with great potential as drug delivery systems, extending the release of the anesthetic (> 48 h) and reducing TTC cytotoxicity against Balb/c 3T3 cells. (AU)

• FAPESP's process: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/25372-0 - Development of nanostructured lipid carriers encapsulating local anesthetics processed biopolymeric matrices for topical application at oral mucosa
• Grantee: Lígia Nunes de Morais Ribeiro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral