Comparison of the cidal activity of tea tree oil and terpinen-4-ol against clinical bacterial skin isolates and human fibroblast cells

Aim: The aim of this study was to compare both the antimicrobial activity of terpinen-4-ol and tea tree oil (TTO) against clinical skin isolates of meticillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (CoNS) and their toxicity against human fibroblast cells.

Tackling antibiotic resistance: a dose of common antisense?

Resistance to antimicrobial agents undermines our ability to treat bacterial infections. It attracts intense media and political interest and impacts on personal health and costs to health infrastructures. Bacteria have developed resistance to all licensed antibacterial agents, and their ability to become resistant to unlicensed agents is often demonstrated during the development process. Conventional approaches to antimicrobial development, involving modification of existing agents or production of synthetic derivatives, are unlikely to deliver the range or type of drugs that will be needed to meet all future requirements. Although many companies are seeking novel targets, further radical approaches to both antimicrobial design and the reversal of resistance are now urgently required. In this article, we discuss ‘antisense’ (or ‘antigene’) strategies to inhibit resistance mechanisms at the genetic level. These offer an innovative approach to a global problem and could be used to restore the efficacy of clinically proven agents. Moreover, this strategy has the potential to overcome critical resistances, not only in the so-called ‘superbugs’ (methicillin-resistant Staphylococcus aureus, glycopeptide-resistant enterococci and multidrug-resistant strains of Acinetobacter baumannii, and Pseudomonas aeruginosa), but in resistant strains of any bacterial species.

Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution.

In this study, we used optical coherence tomography (OCT) to extensively investigate, for the first time, the effect that microneedle (MN) geometry (MN height, and MN interspacing) and force of application have upon penetration characteristics of soluble poly(methylvinylether-co-maleic anhydride, PMVE/MA) MN arrays into neonatal porcine skin in vitro. The results from OCT investigations were then used to design optimal and suboptimal MN-based drug delivery systems and evaluate their drug delivery profiles cross full thickness and dermatomed neonatal porcine skin in vitro. It was found that increasing the force used for MN application resulted in a significant increase in the depth of penetration achieved within neonatal porcine skin. For example, MN of 600 µm height penetrated to a depth of 330 µm when inserted at a force of 4.4 N/array, while the penetration increased significantly to a depth of 520 µm, when the force of application was increased to 16.4 N/array. At an application force of 11.0 N/array it was found that, in each case, increasing MN height from 350 to 600 µm to 900 µm led to a significant increase in the depth of MN penetration achieved. Moreover, alteration of MN interspacing had no effect upon depth of penetration achieved, at a constant MN height and force of application. With respect to MN dissolution, an approximate 34% reduction in MN height occurred in the first 15 min, with only 17% of the MN height remaining after a 3-hour period. Across both skin models, there was a significantly greater cumulative amount of theophylline delivered after 24 h from an MN array of 900 µm height (292.23 ± 16.77 µg), in comparison to an MN array of 350 µm height (242.62 ± 14.81 µg) (p < 0.001). Employing full thickness skin significantly reduced drug permeation in both cases. Importantly, this study has highlighted the effect that MN geometry and application force have upon the depth of penetration into skin. While it has been shown that MN height has an important role in the extent of drug delivered across neonatal porcine skin from a soluble MN array, further studies to evaluate the full significance of MN geometry on MN mediated drug delivery are now underway. The successful use of OCT in this study could prove to be a key development for polymeric MN research, accelerating their commercial exploitation.