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Comparison between top-down and bottom-up processes for the production of functional liposomes applied on the genic vaccination agaist tuberculosis

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Author(s):
Julia Exaltação Trevisan
Total Authors: 1
Document type: Master's Dissertation
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Química
Defense date:
Examining board members:
Maria Helena Andrade Santana; Mário Ricardo Gongora Rubio; Giuliana Piovesan Alves
Advisor: Lucimara Gaziola de la Torre; Maria Helena Andrade Santana
Abstract

The work presents a comparative study of scalable process with a top-down (comminution) and bottom-up (synthesis) approach, aiming the production of functional liposomes for the genetic vaccination against tuberculosis. For the top-down approach, liposomes were produced through the feed of a phospholipid in water solution and simultaneous comminution by cowls (C) and Ultra-Turrax® (U-T) mechanical dispersers. The liposomes obtained by U-T were then submitted to greater levels of shear through the processing in tortuous microchannels under a pressure in the order of 100 atm, in a microfluidizer (M). The influence of the operational variables on the diameter, polydispersity and zeta potential was analyzed through statistics factorial planning and response surface. For C and U-T the effects of shear overcame the effects of feed flow rate, and for M the effects of shear had greater influence than the number of passes.The applied hear rate varied in the range of 102 a 7.106 s-1, resulting in liposomes with mean diameter of 957 to 90 nm, polydispersity of 0,60 to 0,25 and zeta potential of -60 to -44 mV. The mean diameter varied with the inverse of the square root of the shear rate applied. In the bottom-up process liposomes were produced continuously at the interface ethanol/phospholipid and water, formed by the hydrodynamic focusing in a straight microchannel with 0,14 mm of width. The liposome formation velocity varied with the ethanol/water flow ratio, the lipid concentration and composition. The original physico-chemical properties of the functional liposomes were approximately reproduced in both scalable approaches. Comparatively, the top-down approach was more robust, easy to operate and allows the use of high lipid concentration (400 mM), achieving a greater productivity. However, it is discontinuous and requires a higher energetic consumption. The bottom-up approach is less robust, is stably operated with lower lipid concentration (100 mM), but it is a continuous production with a low energetic consumption (AU)

FAPESP's process: 08/07609-2 - Comparison between top down and bottom up processing to the scaling up of the production of functional liposomes for genetic vaccination against tuberculosis
Grantee:Julia Exaltação Trevisan
Support Opportunities: Scholarships in Brazil - Master