Synthesis, engineering and development of nano/micro antibacterial composites for drug delivery
Antibiotic resistance is one of the greatest health concerns worldwide. Data shows within the last 50 years, the number of species and strains of pathogenic and commensal bacteria resistant to antibiotics, has increased virtually monotonically worldwide. Research presented here shows successful synthesis of polymeric drug composites for antibacterial drug delivery, using the electro hydrodynamic atomization technique (EHDA). A biodegradable polymer poly (lactic-co-glycolic acid) (PLGA) proved to be suitable for sustained drug delivery. Materials added to the polymeric composites included the active agent amoxicillin (AMX) and metallic nanoparticles varying in size and morphology. Upon successful synthesis, the drug release, antibacterial efficacy and cell culture data, collated, confirmed the EHDA process is a good alternative method for synthesising antibacterial composite formulations. It is an easy one step process, regardless of the number of excipients added, and also allows for encapsulation of poorly soluble drugs. The first step was to synthesise metallic nanoparticles; varying in shape and size, this would help determine if differences in shape and size of nanoparticles will have an effect on drug content and release data, as well as antibacterial efficacy. Therefore, three types of metals were chosen for their varying antibacterial activity; silver, gold and copper. Silver was synthesised varying in shape and size, including spherical, wire and polygonal or edged. Upon successful synthesis, the next step was to formulate suspensions, made up of PLGA and AMX, along with the varying metallic nanoparticles to electrospray. Two different solvents were used acetone and dichloromethane (DCM), the varying differences in characteristic qualities like electrical conductivity and viscosity, allowed for determination of a stable spray. Results showed the best solvent to use between the two was acetone due to a much higher electrical conductivity and lower viscosity. Thereafter, the composite samples collected were analysed. Drug loading for the formulation containing PLGA and AMX (F2) only was 1.18%, but with the addition of different metallic nanoparticles it increased up to 2.57%. Drug release for F2 was at 18.6% and increased up to 56.1% depending on metallic nanoparticle added. Metallic nanoparticles exhibit antibacterial efficacy, with AgNPs showing the greatest antibacterial activity, confirmed through disk diffusion zone sizes. Antibacterial activity enhancement was proved by formulations containing silver nanoparticles, showing increased activity against S. aureus through increased disk diffusion zones compared to using AMX and silver nanoparticles on their own. AgNPs against S. aureus gave an average inhibition zone of 18.8 mm when compared to CuNP which only gave an average inhibition zone size of 16.07mm. Full formulation containing PLGA AMX and edge shaped silver nanoparticles (F5) proved to have the highest antibacterial efficacy when compared to the other formulations. This was explained through an increase in surface area to volume ratio of the silver nanoparticles, when compared to the spherical and wire shaped nanoparticles. Cell culture data namely the MTT assay also showed (F5) had a cell viability of 71%, this displays promising signs for this formulation for future use as an antibacterial agent.
- PhD