Investigations of nano and microparticles for drug and protein delivery produced by atomisation of biopolymer solutions

Encapsulation of small molecule drugs and proteins has been investigated extensively to improve bioactive formulation, release behaviour, drug stability and drug absorption. Encapsulation of small molecule therapeutics, macromolecular entities and vaccine antigens into biopolymer micro- and nano- particle systems has been widely investigated as a promising strategy to overcome the challenges of oral administration. The work described in this thesis is a contribution to this important field of research. Gelatin nanoparticles have raised much interest for oral formulations to improve the bioavailability of immunosuppressants, to achieve gene delivery and transfection in specific regions of the gastrointestinal (GI) tract and to encapsulate fragile macromolecules such as protein and peptide drugs. Aerosolisation and solvent extraction techniques were used to study the production of gelatin nanoparticles using air brush techniques and a nozzle spray system (Chapter 2). Spherical nanoparticles with discrete sizes in range of 50-155 nm were produced. The ability to control the nanoparticle size within tight limits and stabilisation of the nanoparticles by treatment with glycerol offers advantages for oral delivery of biopharmaceuticals. Microencapsulation of small molecule drugs (gentamicin sulphate antibiotic, ibuprofen NSAID (Chapter 3), propranolol HCl antihypertensive (Chapter 4)) and macromolecular actives (lysozyme and insulin (Chapter 5)) was accomplished using a novel impinging aerosols technique. Alginate displays impressive physicochemical properties and ‘clean and green’ credentials and has been investigated extensively for many years in the pharmaceutical and biomedical sciences. Apart from their advantageous properties of biocompatibility and non-toxicity (alginate possesses ‘generally recognised as safe’ (GRAS) status), alginate polymers exhibit a unique property of forming gels in mild, aqueous conditions at room temperature using divalent metal ions, principally calcium, as crosslinking agents. Microencapsulation of a hydrophilic active (gentamicin sulphate) and a hydrophobic NSAID (ibuprofen) in alginate gel microspheres was accomplished by molecular diffusion of the drug species into microspheres produced by impinging aerosols of alginate solution and CaCl2 cross-linking solution. A mean particle size in the range of 30-50 µm was obtained and high drug loadings of around 35% and 29% weight/dry microspheres weight for gentamicin sulphate and ibuprofen respectively. Released gentamicin sulphate was found to retain at least 80% activity against Staphylococcus epidermidis while Ibuprofen retained around 50% activity against Candida albicans. Direct encapsulation of propranolol HCl in alginate gel microspheres was achieved using the impinging aerosols technique. Environmental Scanning Electron Microscopy (ESEM) revealed smooth spherical hydrated microspheres (40-50 µm) in diameter. Microspheres formulated using the lowest CaCl2 crosslinking concentration (0.1M) exhibited the highest drug loading (14%, w/w of dry microspheres) and highest encapsulation efficiency (66.5%). Minor propranolol release