Microscopy characterisation of micro- and nanosystems for pharmaceutical use

Abstract

technique for characterising microparticles and nanosystems recently developed by our research group. In particular, polyester or acrylic polymer microparticles for fenretinide administration are presented here. Moreover, with regard to nanosystems, solid lipid nanoparticles, nanostructured lipid carriers for prednisone and clotrimazole administration and monooleine aqueous dispersion are discussed. Methodology Microparticles were produced by the ‘solvent evaporation method’. Solid lipid nanoparticlesand nanostructured lipid carriers were prepared by stirring, followed by ultrasonication. Monooleine aqueous dispersionswere produced by the hydrotrope or by the hot homogenization methods. For scanning electron microscopyanalysis, microparticles were metallized by gold coating (Edwards Sputter coat-ing S150) and visualized at 15 – 20 kV with a 360 Stereoscan (Cambridge Instruments, Cambridge, UK). For Cryo-TEM ­analysis­ samples­were­ vitrified­ and­ transferred to a Zeiss EM922Omega (Zeiss SMT, Oberkochen, Germany). Images were recorded by a CCD digital camera (Ultrascan 1000, Gatan) and analyzed using a GMS 1.8 software (Gatan). Conclusion Microscopy is to be considered as an indispensable tool to study drug delivery systems. In particular, scanning electron microscopy is helpful in giving information about micro-sized powders, allowing to identify microspheres and microcapsules, as well as to obtain size distribution of the observed particles. Introduction Microand nanoparticles have attracted pharmaceutical interest in the last decades since they offer a number of advantages with respect to other delivery systems such as: (a) the ability to maintain unaltered physicochemical characteristics for long periods allowing long-term storage; (b) the possible administration through different ways (oral, intramuscular or subcutaneous) depending on their composition and (c) their suitability for industrial production1. Concerning nanosystems, lipid dispersions possess a potential use as matrixes able to dissolve and deliver active molecules in a controlled fashion, thereby improving their bioavailability and reducing side-effects2. In particular, solid lipid nanoparticles (SLN) are delivery systems in which the nano-dispersed phase has a matrix of crystalline solid lipids. SLN are able to protect encapsulated molecules from degradation and modulate their release3,4. Another generation of SLN is represented by nanostructured lipid carriers (NLC) whose matrix is composed of a mixture of solid–liquid lipids able to better solubilise lipophilic drugs5,6. Another type of lipid dispersion able to provide matrices for sustained­ drug­ release­ is­ typified­ by­ monooleine aqueous dispersions (MAD). MAD are heterogeneous systems generated by the dispersion of an amphiphilic lipid, such as monoolein, in water. They are constituted of complex lyotropic liquid crystalline nanostructures like micellar, lamellar, hexagonal and cubic phases, the predominance of one species over Abstract Introduction This review provides an overview of the use of microscopy as a tool to characterise shape and dimension of micro and nanoparticulate systems. In­ the­ pharmaceutical­ field,­ the­ use of microscopy has been exerted an important role since the advent of micro and nanotechnology. Indeed, the morphology of particles and their­ inner­ structure­ does­ influence­ the modalities of administration and release of encapsulated drugs. Scanning electron microscopy can be employed to study the morphology of dry powders. In particular microparticles made of polymers can be well visualised and their diameters can be measured. By cutting the powder during sample preparation, it is possible to obtain important information about the inner morphology of the microstructures, discriminating either the capsule or the sphere microstructure. Cryo transmission electron microscopy is a precious tool for characterising colloidal systems. In particular, external as well as internal shape of nanoparticulate systems such as solid lipid nanoparticles or lyotropic mesophases can be well identified.­Moreover,­size­of­disperse­ phase and the overall structure of the dispersion can be monitored. We provide an overview about the use of electron microscopy as