SIS Group Member Barbara Conway
Wed, 03 Apr 2013 14:13:00 BST
When I was invited to join the SIS group at the University of Huddersfield, I viewed it as an exciting opportunity to bring together all so many aspects of research across the University under one banner. It has afforded collaborations between pharmaceutics (my area), nursing and engineering alongside biological and microbiological aspects.
I am part of a team of talented researchers in formulation and drug delivery here at Huddersfield. Although oral administration remains the first-choice route for drug delivery, transport of drugs to, and through, the skin has an important role in current clinical applications and in maximising the potential of new therapies. The transdermal route can be used to deliver drugs systemically avoiding first-pass metabolism in the liver. In addition, transdermal drug delivery systems are non-invasive and can be self-administered, replacing the requirement for injections which are painful, can pose the risk of disease transmission by needle re-use, especially in developing countries and generate potentially dangerous medical waste. A further advantage of a transdermal drug delivery route system is that it can provide a controlled release of the drug into the patient for extended durations and may improve patient compliance. The transdermal route is indeed desirable, but there is one major obstacle: a primary function of the skin is to provide an effective barrier against the absorption of unwanted chemicals and micro-organisms into the body. For transdermal delivery, drugs must pass through the two sublayers of the epidermis (outer skin structure) to reach the microcirculation of the dermis and into the systemic circulation. The stratum corneum provides the most significant barrier to drug diffusion and we can use physical means (e.g. iontophoresis and sonophoresis) and chemical means (penetration enhancers) to try and disrupt the barrier to improve delivery into the skin.
At Huddersfield, we use a range of drug delivery systems including solid lipid nanoparticles (SLNs) and nanoemulsions for the enhancement of drug penetration into the skin. These nanostructures, formulated from non-toxic materials, can be used to carry both lipophilic and hydrophilic drugs across the stratum corneum and to target different sites within the skin.
In addition to being a barrier against unwanted chemicals, the skin also protects us from microbiological challenges. Commensal micro-organisms colonising the skin reside not only on the external surface but are also found to inhabit hair follicles and sites beneath the skin surface. In addition to the microbial challenges from the external environment such resident organisms can cause infection when the protective skin barrier is breached in a wound or surgical procedure. Effective skin and wound antisepsis is therefore required for preventing associated infections and an efficient and rapid permeation of the applied antiseptic agent into the deeper layers of the skin is essential in preventing infections associated with invasive procedures. Chlorhexidine gluconate (CHG) is one of the most widely used antimicrobials within clinical practice for skin antisepsis and EPIC 2, a Department of Health-commissioned systematic review and guidelines for preventing healthcare associated infections (HCAI) currently recommends use of 2% chlorhexidine in alcohol for skin preparation.
CHG has a broad spectrum of activity with low levels of toxicity following application to surfaces including topical and environmental. Whilst chlorhexidine in alcoholic solution has been shown to have superior antimicrobial activity compared to aqueous solutions, its efficacy in reducing catheter colonisation and infection is comparable and we have demonstrated the limited permeation of CHG following application of either alcoholic or aqueous solutions in human skin. Moreover, the negligible concentrations of chlorhexidine detected at skin depths of >300 µm may indeed allow for microorganisms residing in the deeper layers, for example around hair follicles, to survive the skin antisepsis procedures recommended in the current guidelines. Interestingly, the results of our recent studies have suggested that the penetrative properties of CHG may be significantly improved when combined some essential oils, e.g. with eucalyptus oil (EO). The antimicrobial efficacy of essential oils has been known for several years and many studies have demonstrated activity against bacteria, fungi and viruses. More recently, in the light of increased antimicrobial resistance within the clinical setting, the potential of essential oils for the prevention and treatment of infection has been researched in several studies. We have demonstrated a synergistic antimicrobial activity of CHG and essential oils in human skin and we have shown that the combination of eucalyptus oil and chlorhexidine applied at the skin surface increases both the rate and extent of delivery of chlorhexidine within the deeper skin layers. Such synergistic combinations may aid in preventing infection and microbial re-colonisation of the skin in clinical practice following invasive procedures.
These persisting microorganisms in the skin layers can also act as a nidus to contaminate central venous catheters (CVCs), particularly at the time of insertion, resulting in localized or even systemic infection. CVC-related infections are a major cause of bacteraemia and sepsis (up to almost 40% of the all blood stream infections in England are CVC-related). We investigate the incorporation and control of release of drugs and antiseptic agents into medicated dressings such as hydrogels to reduce infection rates. We are also designing multifunctional delivery matrices for skin repair, able to promote wound healing and at the same time release an active substance onto the wound site in a controlled way
