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Citotoxicity and in vivo anesthesia effect of functional nanostructured lipid carriers loaded with S75:R25 bupivacaine, designed for burn treatment

Grant number: 18/07100-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2018
Effective date (End): July 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Eneida de Paula
Grantee:Gabriela Geronimo
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , 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


Pain control in burn injuries and their treatment remains a difficult challenge. Opioid therapy, although often used, has several limitations. An alternative to meet such demand is the application of local anesthetics, which are potential drugs for the treatment of such injuries. Bupivacaine is the local anesthetic most used worldwide in surgeries and postoperative periods, with a time of action of up to 6 hours. However, this time of action is not enough for the burning pain treatment, requiring the anesthetic to be applied several times a day, what may enhance its systemic toxicity. Drug-delivery carriers such as nanostructured lipid carriers (CLN) can overcome such limitations. The present project proposes the evaluation of cytotoxicity and in vivo anesthetic effect of optimized CLN formulations, composed of functional natural excipients (beeswax, lavender and melaleuca essential oils). Such CLNs were prepared for the encapsulation of bupivacaine (1%) in its enantiomeric-excess form: S75:R25. The samples will be evaluated regarding the in vitro cytotoxicity - over 3T3 and HCAT cells - and anesthetic effect in mice, trough the tail flick test. We propose, therefore, to perform in vitro and in vivo tests necessary for the development of these innovative anesthetic formulations.

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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)
GERONIMO, GABRIELA; RODRIGUES DA SILVA, GUSTAVO H.; DE MOURA, LUDMILLA D.; RIBEIRO, LIGIA N. M.; GUILHERME, VIVIANE A.; MENDONCA, TALITA C.; CASTRO, SIMONE R.; BREITKREITZ, MARCIA C.; DE PAULA, ENEIDA. Development of S75:R25 bupivacaine-loaded lipid nanoparticles functionalized with essential oils for treating melanoma. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 96, n. 8, p. 2197-2207, . (14/14457-5, 18/07100-4, 17/15174-5)
RODRIGUES DA SILVA, GUSTAVO H.; GERONIMO, GABRIELA; RIBEIRO, LIGIA N. M.; GUILHERME, VIVIANE A.; DE MOURA, LUDMILLA DAVID; BOMBEIRO, ANDRE L.; OLIVEIRA, JULIANA DAMASCENO; BREITKREITZ, MARCIA C.; DE PAULA, ENEIDA. Injectable in situ forming nanogel: A hybrid Alginate-NLC formulation extends bupivacaine anesthetic effect. Materials Science & Engineering C-Materials for Biological Applications, v. 109, . (18/07100-4, 14/25372-0, 17/15174-5, 14/14457-5)

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