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Production of polymeric microparticles by supercritical fluid technology for application as vehicle for oral administration of 17'alfa'-methyltestosterone to Nile tilapia

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Author(s):
Priscila Soares Costa Sacchetin
Total Authors: 1
Document type: Doctoral Thesis
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Química
Defense date:
Examining board members:
Angela Maria Moraes; Ana Rita Morales; Flavio Faria de Moraes; Julian Martínez; Silvia Helena Prado Bettini
Advisor: Paulo de Tarso Vieira e Rosa; Angela Maria Moraes
Abstract

In this work, the aim was to produce oral carriers consisting of the synthetic polymers PLA (poly(L-lactic acid)), PLGA (poly(50/50 DL-lactide-co-glycolide)) and PCL (polycaprolactone) by the precipitation of the polymer solutions using supercritical CO2 as an antisolvent for the controlled release of 17?-methyltestosterone (MT). The influence of pressure, hormone and polymers concentration, as well as of the flow rate of the polymer solution on the formation of these devices was analyzed. PLA particles with diameters between 5.4 to 20.5 mm were efficiently produced; increases in the concentration of the polymer solution resulted in smaller particles, while increasing the flow rate of polymer solution caused an increase in particle mean diameter. No significant effects on morphology and size distribution of the particles were observed with pressure variation. Changes in the mechanical and physical characteristics of the PLA particles were also noticed, as reduction in the glass transition temperature of the polymer. PLA particles prepared in the presence of MT showed larger average diameters and changes in surface morphology. The presence of MT did not result in changes of the glass transition and fusion temperatures of the particles. Zeta potential analyzes showed that the particles have a strong tendency to flocculate when exposed to aqueous solutions. PLA/PCL particles were obtained from the mixture of these polymers at ratios from 1/9 to 1/1 w/w. High concentrations of PCL caused increased formation of particles with greater mean diameters, which were rougher and had a higher tendency to aggregate. The incorporation efficiency of MT ranged from 25.6 to 64%, accompanied by an increase in mean diameter. Changes in the thermal behavior of the particles were observed when high concentrations of MT were used, which led to the formation of more amorphous structures. PLA/PLC particles were not stable when subjected to tests of zeta potential. PLA/PLGA particles were also produced, with mean diameters ranging from 23 to 98 mm. The incorporation efficiency of MT was also broad, varying from 41 to 90%. The process affected the crystallinity of the particles, and the presence of MT led to more amorphous and porous structures. The behavior of the PLA, PLA/PCL and PLA/PLGA particles regarding the in vitro release kinetics of MT was analyzed through exposure of the obtained systems to different pH conditions. The lowest release rates were observed for PLA particles, while the PLA/PCL and PLA/PLGA particles showed similar performances. It was observed that the theoretical amount of particles needed for the sex reversal treatment of tilapia varied according to the composition of the devices (polymer type and ratio, as well the quantity of MT). Depending on the device, the daily required amounts of particles can vary between 34-88 g particles/kg of fish feed (AU)

FAPESP's process: 08/11622-4 - Production of polymeric microparticles by supercritical fluid technology as vehicles for hormonal oral delivery to Nile Tilapia
Grantee:Priscila Soares Costa Sacchetin
Support Opportunities: Scholarships in Brazil - Doctorate