Preparation of gas-filled porous microparticles (GPPs) and microbubbles (MBs) by PGSS method

• Author(s): Lopes, Daniel Deodato
• Date: 2012
• Persistent ID: http://hdl.handle.net/10362/9318
• Origin: Repositório Institucional da UNL
• Subject(s): Microbubbles; Supercritical fluids; PGSS; PFC; Gas encapsulation
• Document Type: Master thesis
• Language: English
• Advisor(s): Duarte, Catarina
• Contributor(s): RUN

Description

Dissertation to obtain the Master Degree in Biotechnology

The main goal of this Project was the development of microbubbles (MBs) and gas-filled porous particles (GPPs) by supercritical fluids (SCF) processes, namely particles from gas saturated solution (PGSS). MBs of perfluorcarbons (PFC) are currently used as contrast agents in ultrasound imaging and as ultrasound-guided drug delivery for targeted therapeutic applications. They are normally produced by processes that present some limitations. The SCF processes are an innovative technology for the production of these MB’s that has not yet been exploited and can overcome these limitations. Carriers are used to prevent rapid diffusion of the gas out of the particle. In the first part of this thesis, a preliminary selection of carrier materials was carried out, including lipids of different hydrophilic-lipophilic balance (HLB) and hydrophilic polymers. Their behavior in the presence of PFC and mixtures of PFC and sc-CO2 was qualitatively studied. A lipid of high HLB value, Gelucire 50/13, was selected to produce the GPPs by PGSS. Main parameters of the process, temperature and pressure, were studied in the range from 55ºC to 80ºC and from 8,5 MPa to 15,4 MPa. Besides, the carrier:PFC ratio and the molecular structure of the PFC were investigated. Particle morphology was analyzed by Scanning Electron Microscopy (SEM), and the presence of PFC was determined by Nuclear Magnetic Resonance (NMR). Small and non agglomerated particles were obtained at 80ºC and 8.5 MPa. Cyclic C4F8 was entrapped in lipid particles in higher amount than of linear C3F8. Nevertheless, the stability of particles obtained at the best operating conditions (80ºC and 8.5 MPa), was relatively short (below 3h) being the majority of the gas released in the first hour.