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The water-in-oil-in-water (w/o/w) emulsification process is the method of choice for the encapsulation inside polymeric particles of hydrophilic drugs such as proteins and peptides which are high molecular weight macromolecules. Our objective was to apply this technique in order to formulate nanoparticles loaded with both a hydrophilic and a low molecular weight drug such as propranolol-HCl. Nanoparticles were prepared using a pressure homogenization device with various polymers (poly-e-caprolactone, poly(lactide-co-glycolide), ethylcellulose) and different amounts of drug and were compared in terms of particle size, encapsulation efficiency and drug release. Higher encapsulation efficiencies were obtained with both PCL (77.3%) and PLGA (83.3%) compared to ethylcellulose (66.8%). The in vitro drug release was characterized by an initial burst and an incomplete dissolution of the drug. When decreasing the polymer/drug ratio, the release appeared more controlled and prolonged up to 8 h. It can be concluded that nanoparticles prepared by w/o/w emulsification followed by solvent evaporation might be potential drug carriers for low molecular weight and hydrophilic drugs.

Polymerization of lactide on monomethoxypolyoxyethylene (MPOE), using stannous octoate as a catalyst, was carried out in bulk and in solvent. Polymerization in a solvent permits one to work at a lower temperature and thus to prevent transesterification reactions. The copolymers synthesized in solvent exhibited a lower polydispersity and a polylactic acid (PLA) block longer and closer to the expected one. Therefore, this procedure was used to synthesize a series of diblock copolymers MPOE-D,L-PLA, keeping the PLA chain constant (45,000 g/mol), the MPOE block increasing from 2000 to 5000, 10,000, 15,000, and 20,000 g/mol. The longer the MPOE chain, the higher the water uptake in the MPOE-PLA films and the lower the glass transition temperature of the copolymers. The synthesized copolymers were used to prepare microspheres by the double-emulsion method. The PLA microspheres possess a smooth surface, whereas those made from copolymers have a rough surface with irregularity increasing with the molecular weight of MPOE. The size of these microspheres depends on the amphiphilic nature of the copolymers, their hydrophilicity, and their intrinsic viscosity in the organic solvent.

Microcapsules with an oil core surrounded by a polymeric shell have been prepared by the controlled phase separation of polymer dissolved within the oil droplets of an oil-in-water emulsion. The dispersed oil phase consists of the shell polymer (polystyrene), a good solvent for the polymer (dichloromethane), and a poor solvent for the polymer (typically hexadecane). Removal of the good solvent results in phase separation of the polymer within the oil droplets. If the three interfacial tensions between the core oil, the shell-forming polymer, and the continuous phase are of the required relative magnitudes, a polymer shell forms surrounding the poor solvent. A UV-responsive organic molecule was added to the oil phase, prior to emulsification, to investigate the release of a model active ingredient from the microcapsules. This molecule should be soluble in the organic core but also have some water solubility to provide a driving force for release into the continuous aqueous phase. As the release rate of the active ingredient is a function of the thickness of the polymeric shell, for controlled release applications, it is necessary to control this parameter. For the preparative method described here, the thickness of the shell formed is directly related to the mass of polymer dissolved in the oil phase. The rate of volatile solvent removal influences the porosity of the polymer shell. Rapid evaporation leads to cracks in the shell and a relatively fast release rate of the active ingredient. If a more gentle evaporation method is employed, the porosity of the polymer shell is decreased, resulting in a reduction in release rate. Cross-linking the polymer shell after capsule formation was also found to decrease both the release rate and the yield of the active ingredient. The nature of the oil core also affected the release yield.

MPOE-PLA microspheres containing bovine serum albumin (BSA) were prepared by the double emulsion method with high encapsulation efficiency ( approximately 93%). Confocal scanning microscopic analysis using MPOE-PLA labelled with 1-pyrenemethanol showed the MPOE coating of the microsphere surface. This coating improves the performance of the release system compared with PLA microspheres; the hydrophilic chains reduce the BSA adsorption onto the microspheres and increase the amount of BSA released in the supernatant. Microsphere analysis using atomic force microscopy showed that the presence of the MPOE chains also leads to surface roughness. Studies of the diffusion of 1% rhodamine aqueous solution into the microspheres by means of confocal microscopy showed a fast diffusion of water through the matrices containing high molecular weight MPOE chains (?10 000 g mol-1) and could explain the fast release of BSA from these microspheres.