Healthcare associated infections are a major concern within the health services as they inflict a significant financial burdens and time constraints on the healthcare system. Effective skin antisepsis prior to incision of the skin, for example, during surgery, is essential in preventing subsequent infection. Current evidence-based guidelines recommend the use of 2 % (w/v) chlorhexidine digluconate (CHG), preferably in 70 % (v/v) isopropyl alcohol (IPA) prior to incision of the skin. However, many antimicrobial agents poorly permeate into the skin and microorganisms residing in the deeper layers and around hair follicles, may survive the procedure and cause infection. Lipid-based nanocarriers are promising drug delivery system with the potential to improve chemical stability, control drug release and alter drug pharmacokinetics. In present study, the ability of lipid-based nanocarriers to enhance the skin retention of antimicrobial agents was accessed. The solid lipid nanoparticles (SLNs) and nanoemulsions (NEs) of triclosan (TSN) and chlorhexidine digluconate (CHG) were prepared and compared based on their physicochemical parameter and better skin retention properties. SLNs of TSN was prepared using glyceryl behenate (GB) and glyceryl palmitostearate (GP) solid lipids, while NEs of TSN and CHG were prepared using eucalyptus oil (EO) and olive oil (OO) with combination of surfactants Tween® 80 and Span® 80. Characterisation and optimisation of SLN and NE formulations to find better skin retention ability is described with various other studies within this thesis. Skin permeation of TSN and CHG was subsequently investigated by in vitro Franz diffusion model using artificial membrane and full thickness porcine ear skin and the penetration profile were determined by differential stripping technique to quantify the amount of drug retained within skin. In both SLN and NE formulations, no detectable level of TSN and CHG was found in receiver medium through full thickness porcine ear skin in 24 h, which is advantageous for topical drug delivery system. SLNs prepared with GP, as solid lipid was able to produce smaller size formulation along with better skin penetration compared with GB-SLNs formulation. SLNs and NEs of TSN was analysed and compared for enhanced skin retention properties. The results demonstrated a significantly enhanced skin penetration of TSN for NE formulations compared to SLNs, which might be due to difference in composition and physical state of lipids and physicochemical parameter of formulations. In case of CHG-loaded NEs, the results demonstrated EO show better skin penetration compared to OO formulations due to its skin penetration enhancing property, which might be beneficial for skin antisepsis prior to invasive procedure to reduce the microorganisms on and within the skin. However, further studies are required to study antibacterial effects of nanoformulations against various skin microorganisms, to analyse skin permeation and retention ability of prepared nanoformulations in in vivo diffusion studies and further studies to analyse toxicity and skin tolerance of EO alone or in combination with antimicrobial agents.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:688337 |
| Date | January 2016 |
| Creators | Kakadia, Pratibha G. |
| Contributors | Conway, Barbara |
| Publisher | University of Huddersfield |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.hud.ac.uk/id/eprint/28705/ |
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