Microfluidic Assembly of pDNA/Cationic Liposome Lipoplexes with High pDNA Loading for Gene Delivery

Autor(es)

Balbino, Tiago A. ^[1] ; Serafin, Juliana M. ^[1] ; Malfatti-Gasperini, Antonio A. ^[2] ; de Oliveira, Cristiano L. P. ^[3] ; Cavalcanti, Leide P. ^[1] ; de Jesus, Marcelo B. ^[4] ; de La Torre, Lucirnara G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Sch Chem Engn, BR-13083970 Campinas, SP - Brazil

^[2] CNPEM, Brazilian Synchrotron Light Lab, BR-13083100 Campinas, SP - Brazil

^[3] Univ Sao Paulo, Inst Phys, BR-05508 Sao Paulo, SP - Brazil

^[4] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Langmuir; v. 32, n. 7, p. 1799-1807, FEB 23 2016.
• Citações Web of Science: 7

Resumo

Microfluidics offers unique characteristics to control the mixing of liquids under laminar flow. Its use for the assembly of lipoplexes represents an attractive alternative for the translation of gene delivery studies into clinical trials on a sufficient throughput scale. Here, it was shown that the microfluidic assembly of pDNA/cationic liposome (CL) lipoplexes allows the formation of nanocarriers with enhanced transfection efficiencies compared with the conventional bulk mixing (BM) process under high pDNA loading conditions. Lipoplexes generated by microfluidic devices exhibit smaller and more homogeneous structures at a molar charge ratio (R +/-) of 1.5, representing the ratio of lipid to pDNA content. Using an optimized model to fit small-angle X-ray scattering (SAXS) curves, it was observed that large amounts of pDNA induces the formation of aggregates with a higher number of stacked bilayers (N similar to 5) when the BM process was used, whereas microfluidic lipoplexes presented smaller structures with a lower number of stacked bilayers (N similar to 2.5). In vitro studies further confirmed that microfluidic lipoplexes achieved higher in vitro transfection efficiencies in prostate cancer cells at R +/- 1.5, employing a reduced amount of cationic lipid. The correlation of mesoscopic characteristics with in vitro performance provides insights for the elucidation of the colloidal arrangement and biological behavior of pDNA/CL lipoplexes obtained by different processes, highlighting the feasibility of applying microfluidics to gene delivery. (AU)

• Processo FAPESP: 11/19952-6 - Caracterização estrutural de sistemas anfifílicos com aplicação industrial utilizando espalhamento de raios x a baixos ângulos e técnicas complementares
• Beneficiário: Antonio Augusto Malfatti Gasperini
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/23143-9 - Sistemas microfluídicos para a produção de nanopartículas multifuncionais destinadas à terapia e vacinação gênica
• Beneficiário: Tiago Albertini Balbino
• Modalidade de apoio: Bolsas no Brasil - Doutorado