Production and characterization of loaded smart microcapsules, performance evaluation and industrialization of supercritical CO2 based processes

Abstract

In the last years, scientists and engineers have designed a wide range of polymeric systems capable responding to internal or external stimuli. There is a great range of responsive polymers that are sensitive to different stimuli such as light, temperature, electric field, magnetic field, pH and chemicals, etc. This kind of polymers are usually called also “smart polymers” or “intelligent polymers”; they have many applications in biology and medicine fields and can be used as sensor and biosensors, for controlled and trigger drug delivery, environmental remediation, chemo-mechanical actuators, and others. Among several use of smart polymers, their use as micro and nano structured devices in nutraceutical and pharmaceutical field, in rigenerative medicine, in the oil-gas industry and, for example, in the lubricants field, in the self-healing is very interesting and still poorly investigated. In detail, a new approach for protection of the additives from thermo-oxidative degradation was proposed, using additive loaded microcapsules produced using a supercritical techinique. These structures can allow to enhance the stability and to prolong the lifetime of the additives, reducing their volatility and reactivity and/or to maintain the additive concentration constant during operation, controlling their release. Two additives proposed by Total were studied: an antioxidant (AM) and a friction modifier (MoDTC). Spherical and regular nanocapsules with mean diameters of 195±12 nm-189±10 nm and AM loading of 0.4 g- 0.73 g AM/g PMMA with EE of 57-95% were produced using Supercritical Emulsions Extraction (SEE-C) process. AM loaded microcapsules the microcapsules showed a good dispersability in base oil and the release of AM is responsive to pH level but also to temperature. Spherical and homogeneous PMMA loaded capsules were produced also using MoDTC. In this case, particles with mean diameter 187±23 nm and EE of 90% were obtained. Regarding the self-healing application, a protective coating for aerospace and automative applications with the intrinsic capability to highlight damages suffered during the operating conditions, using an efficient and green process to produce microcapsules acting as a health-monitoring visual element is proposed. SEE-C technology was used to encapsulate a health-monitoring mixture based on DiGlycidyl Ether of Bisphenol A (DGEBA), dyed with Solvent Red 242, in polymethylmethacrylate polymer (PMMA). A comparison between SEE-C and Solvent Evaporation (SE) was also carried out in term of particle size distribution (PSD), encapsulation efficiency (EE) and stability in the time (TS) of the produced microcapsules. Larger microcapsules, with the size up to 726 nm and the EE below 57% were produced using the SE technology. The best results were obtained using SEE-C: spherical microcapsules with unwrinkled and smooth surface were obtained with mean size of 220 nm and EE up to 79 % using SEE-C. SEE-C capsules preserve their stability for the entire time frame analyzed of 30 days. The protective coating was very sensitive in showing stress areas: impact tests carried out on strips of Carbon Fiber Reinforced Composites (CFRCs) coated with a green aqueous paint in which the SEE-C capsules were previously dispersed showed dye leaking associated with capsule breaking in the stressed areas, even using the low impact energies of 3.8 J and 4.5 J. Controlled delivery of human growth factors is still a challenge in tissue engineering protocols, and poly-lactic acid and poly-lactic-co-glycolic acid carriers have been recently proposed for this purpose. In this study, the microencapsulation of two human growth factors, namely Growth Differentiation Factor -5 (hGDF-5) and Transforming Growth Factor β1 (hTGF-β1), by processing different emulsions using SEE-C technology. Polymer molecular weight, co-polymer ratio and surfactant amount in aqueous phases as well as phases mixing rate were varied to fabricate carriers with suitable size and loadings. Carriers with different mean size from 0.4 ±0.09 μm up to 3±0.9 μm were obtained by SEE-C technology when processing emulsions with different formulations; carriers were also loaded with 3 μg/g and 7μg/g for hGDF-5 and hTGF-β1 and they assured both growth factors controlled release along 25 days. Carriers showed also reduced cytotoxicity when evaluated in Chinese Hamster Ovary cells (CHO-K1); interestingly, they also exhibited a reduced cytotoxicity whit respect to carriers obtained by conventional evaporation technique, and also a low reactivity on human peripheral blood mononuclear cells (hPBMCs), suggesting their safety and potential use in tissue engineering protocols. Finally, the production of composite microspheres loaded with bioactive compounds has been another important challenge handled in this Ph.D. work. In particular, astanxanthin and beta-carotene were selected in this framework for their nutraceutical properties. The main outcome of this investigation was not only the improvement of the bioavailability, but also the protection of the antioxidant activity and shelf life of the bioactive compound. Defined and spherical particles were produced by means of the SEE-C technique using Ethyl Cellulose, PLA and PLGA as carriers. In detail, the SEE-C technology was used to encapsulate astaxanthin in ethyl cellulose (EC), obtained particles with mean size of 363 nm and encapsulation efficiency up to 84%. β-Carotene (β-CA) was encapsulated into poly-lactic-co-glycolic acid (PLGA) and poly-lactic acid (PLA) carriers using SEE-C. α-Tocoferol (α-TOC) and Rosmarinic Acid (RA) were proposed as excipients to improve the formulation. PLA and PLGA carriers with sizes ranges between 1.5±0.5 μm and 0.3±0.07 μm were fabricated with encapsulation efficiencies between 50-80%. The co-encapsulation of α-TOC with β-CA gained to prolonged drug shelf life. Both systems preserved their antioxidant activity against light, heat and oxygen. In conclusion, the SEE-C technique was successfully applied for production of smart microcapsules in several fields, demonstrating to be an attractive and available process from an industrial point of view. [edited by Author]