J. of Supercritical Fluids 55 (2010) 333–339 Contents lists available at ScienceDirect The Journal of Supercritical Fluids journal homepage: www.elsevier.com/locate/supflu Development of functional mesoporous microparticles for controlled drug delivery Rita B. Restani, Vanessa G. Correia, Vasco D.B. Bonifácio ∗ , Ana Aguiar-Ricardo ∗ REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal article info Article history: Received 3 May 2010 Received in revised form 18 August 2010 Accepted 23 August 2010 Keywords: Supercritical carbon dioxide Radicalar polymerization Biocompatible polyesters Mesoporous particles Drug delivery Ibuprofen abstract Mesoporous microbeads can be easily obtained by radical polymerization of biocompatible glyc- erol dimethacrylate (GDMA) in supercritical carbon dioxide. Small mass density microparticles ( = 0.19–0.37 g cm -3 ) with controlled size (1–3 m) and homogeneous morphology are obtained by the addition of different stabilizers to the polymerization media. The microbeads were obtained in quantita- tive yield as white, dry powders directly from the reaction vessel possessing a pollen-like morphology. The (S)-ibuprofen loading (up to 120 mg g -1 ) and release profile from the PGDMA microbeads is highly promising which makes them potential drug delivery vehicles. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Controlled drug delivery technology represents one of the frontier areas of science. These delivery systems offer numerous advantages compared to conventional dosage forms like improved efficacy, reduced toxicity and improved patient compliance and convenience. Pulmonary drug delivery is gathering an increasing importance, especially in the last few years [1] since it is non- invasive in contrast to injection and tends to exhibit less drug degradation than the oral route. This strategy is believed to consti- tute a major breakthrough since a considerable effort is currently being focused on the systemic delivery of therapeutic peptides and proteins via pulmonary delivery because the lungs have large sur- face area, a rich supply of blood, a thin alveolar membrane with very high permeability, and low levels of enzymatic activity [2]. Insulin (for diabetes) is the drug receiving the most intense inter- est for this delivery method as a substitute for injection, because the disease requires long-term management and frequent adminis- tration [3]. The most recent example is the synthesis of an inhaled long-acting neuraminidase inhibitor active (CS-8958) against the influenza virus [4], followed by the announcement of a new dry powder inhaler (DPI) by an international pharmaceutical company to overcome a potential flu pandemic [5]. The performance of dry powder aerosol delivery systems has been improved significantly ∗ Corresponding authors. Tel.: +351 212 949 648; fax: +351 212 948 550. E-mail addresses: vasco.bonifacio@dq.fct.unl.pt (V.D.B. Bonifácio), aar@dq.fct.unl.pt (A. Aguiar-Ricardo). over the last decade through the use of engineered particles that are of low aerodynamic diameters, and/or less cohesive and adhe- sive, leading to high fine particle fraction in the aerosol. Edwards et al. [2] have shown that very light particles (<∼0.4 g cm -3 ) with d >5 m can be efficiently deposited in the lungs. The role of low mass density in rendering respirable large particles can be under- stood in terms of the particles mean aerodynamic diameter, d ae , that is related to the actual sphere diameter d by the formula d ae = d √ . Where d is particle diameter and  is the particle den- sity. These authors also demonstrated that the maximal deposition of monodisperse aerosol particles in the alveolar region occurs for d ae = ∼3 m. If a balance between size and particles were estab- lished, relatively large particles with high porosity could have the same aerodynamic diameter as smaller, nonporous particles they can also avoid the phagocytic clearance from the lungs until the biodegradable polymeric particles have delivered their therapeutic dose. Besides, an increase in the size of particles results in a frac- tional surface area of particle–particle contact in a dry powder (or liquid suspension) and thus in less tendency to agglomerate than (conventional) small and nonporous particles. Following this trends we initiated the development of functional (with hydroxyl free groups) polyester-based polymers, highly attractive due to their biocompatible and biodegradable proper- ties [6]. Glycerol dimethacrylate (GDMA) was the chosen monomer since it is rather hydrophilic and has been used in the synthesis of functional porous polymer monoliths for several applications [7,8]. Moreover, it should be highlighted that GDMA is synthe- sized using glycerol, a by-product in the biodiesel production [9]. Recently GDMA was also used as a crosslinker in the synthesis 0896-8446/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.supflu.2010.08.007