Encapsulation of ropivacaine in a combined (donor-acceptor, ionic-gradient) liposomal system promotes extended anesthesia time

Autor(es)

Goncalves da Silva, Camila Morais ^[1] ; Franz-Montan, Michelle ^[2] ; Gomez Limia, Cintia Elisabeth ^[1] ; de Morais Ribeiro, Ligia Nunes ^[1] ; Braga, Mario Antonio ^[1] ; Guilherme, Viviane Aparecida ^[1] ; da Silva, Camila Batista ^[2] ; Casadei, Bruna Renata ^[1] ; Saia Cereda, Cintia Maria ^[1] ; de Paula, Eneida ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, UNICAMP, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch, Dept Physiol Sci, Piracicaba, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 12, n. 10 OCT 5 2017.
• Citações Web of Science: 9

Resumo

Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH4)(2)SO4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine: cholesterol (2: 1 mol%) and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h) release of ropivacaine, compared to conventional liposomes (similar to 45 h), or plain ropivacaine (similar to 4 h) (p<0.05). The pre-formulations tested were significantly less toxic to 3T3 cells, with toxicity increasing in the order: combined system < ropivacaine in donor or acceptor liposomes < ropivacaine in conventional liposomes < plain ropivacaine. The combined formulation, containing 2% ropivacaine, increased the anesthesia duration up to 9 h after subcutaneous infiltration in mice. In conclusion, a promising drug delivery system for ropivacaine was described, which can be loaded with large amounts of the anesthetic (2%), with reduced in vitro cytotoxicity and extended anesthesia time. (AU)

• Processo FAPESP: 11/21735-3 - Encapsulação de ropivacaína em lipossomas por carregamento remoto em função de gradiente iônico e de pH.
• Beneficiário: Camila Morais Gonçalves da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/14457-5 - Carreadores baseados em lipídios (SLN/NLC e lipossomas com gradiente iônico) como estratégia para aumentar a encapsulação e a potência de anestésicos locais
• Beneficiário: Eneida de Paula
• Modalidade de apoio: Auxílio à Pesquisa - Temático