On Phase Behaviours in Lipid/Polymer/Solvent/Water Systems and their Application for Formation of Lipid/Polymer Composite Particles

• Main Author: Imberg, Anna
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Institutionen för farmaci 2003
• Subjects: Physical chemistry; Biodegradable; CLSM; Composite Particles; Controlled Release; Cubic Phases; Drug Delivery; Flory-Huggins Theory; FT-PGSE-NMR; IPMS; Liquid Phase; Lipid Domains; Liquid Handler; Microspheres; Microstructure; Phase Behaviour; Phase Separation; Polymer Matrix; SAXS; Segregation; Sponge Phase; Swelling; Fysikalisk kemi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3795; http://nbn-resolving.de/urn:isbn:91-554-5816-5

A new kind of lipid/polymer composite particle, consisting of a biodegradable polymer matrix with well-defined lipid domains, has been created. The lipid used is the water-swelling lipid monoolein (MO), which forms a reversed bicontinuous cubic diamond structure in aqueous solutions. The polymer is poly(d,l-lactide-co-glycolide) (PLG), which degrades into water-soluble monomers through hydrolysis. This new particle might be a good alternative for encapsulation of active substances intended to be released over a longer period of time, i.e. sustained/retained/controlled release. To prepare such particles can be difficult. Suitable phase behaviour and a solvent with the right properties are needed. For this reason, the phase behaviours of several different lipid/polymer/solvent/water systems have been explored. From the phase behaviour of a suitable system (i.e. MO/PLG/ethyl acetate/water), a route for formation of lipid/polymer composite particles has been deduced. Particles have been formed and distinct, water-swelling, lipid domains have been confirmed by characterization by means of confocal laser scanning probe microscopy (CLSM). The sample preparation process has been automated and a method based on using a robotic liquid handler has been developed. Phase diagrams have been determined by examination of macroscopic behaviours and the microstructures of the phases have been studied by small- and wide-angle X-ray scattering (L3, V2, Lα, L), nuclear magnetic resonance self-diffusion (L, L3), viscosimetry (L) and rheology (L). Several different theoretical models have been applied for interpretation of the results. For example, the swelling of the reversed bicontinuous cubic phases and the sponge phase have been modelled by applying the theory of infinite periodical minimal surfaces, the sponge phase has been shown to be bicontinuous according to the theory of interconnected rods and the phase behaviour of the polymer has been described by the Flory-Huggins theory. The main focus of this work (4/5) concerns phase studies in multicomponent systems from a physical-chemical point of view.