Improving antimicrobial release kinetics from hydrophobic polymer implants via ion pairing to combat biomedical-device related infection

Purpose The aim of this study is to improve the drug release properties of antimicrobial agents from hydrophobic biomaterials using using an ion pairing strategy. In so doing antimicrobial agents may be eluted and maintained over a sufficient time period thereby preventing bacterial colonisation and subsequent biofilm formation on medical devices. Methods The model antimicrobial agent was chlorhexidine and the selected fatty acid counter ions were capric acid, myristic acid and stearic acid. The polymethyl methacrylate films were loaded with 2% of fatty acid:antimicrobial agent at the following molar ratios; 0.5:1M, 1:1M and 2:1M and thermally polymerized using azobisisobutyronitrile initiator. Drug release experiments were subsequently performed over a 3-month period and the mass of drug released under sink conditions (pH 7.0, 37oC) quantified using a validated HPLC-UV method. Results In all platforms, a burst of chlorhexidine release was observed over the initial 24-hour period. Similar release kinetics were observed between the formulations during the initial 28 days. However, as time progressed, the chlorhexidine baseline plateaued after 56 days whereas formulations containing the counterions appeared to continuously elute linearly with time. As can be observed in figure 1, the rank order of total chlorhexidine release in the presence of 0.5M fatty acid was myristic acid (40%) > capric acid (35%) > stearic acid (30%)> chlorhexidine baseline (15%). Conclusion The incorporation of fatty acids within the formulation significantly improved chlorhexidine solubility within both the monomer and the polymer and enhanced the drug release kinetics over the period of study. This is attributed to the greater diffusivity of chlorhexidine through PMMA in the presence of fatty acids. In th absence of fatty acids, chlorhexidine release was facilitated by dissolution of surface associated drug particles. This study has illustrated the ability of fatty acids to modulate chlorhexidine release from a model biomaterial through enhanced diffusivity. This strategy may prove advantageous for improved medical devices with enhanced resistance to infection.

At the end of the day: Macmillan's account of the Cuban missile crisis

Pre-publicity for the final volume of Harold Macmillan’s memoirs, At the End of the Day, stressed that it would provide the British side of the Cuban missile crisis for the first time. The Churchillian model chosen, changes required by the Cabinet Office and Macmillan’s desire to rebuke those political opponents who claimed that the crisis demonstrated a lack of British influence in Washington, however ensured a focus on his personal relationship with President Kennedy. His larding the text with contemporary observations from his diaries also skewed Macmillan’s account and, in particular, underplayed the significance of British moves at the United Nations in New York to secure a credible United Nations inspection regime and a US guarantee of the inviolability of Cuba. Careful reconstruction of Macmillan’s real-time experience of the Cuban missile crisis demonstrates the limitations of his own account of this event

Modifying “a very dangerous message": Britain, the non-aligned and the UN during the Cuban missile crisis

This chapter analyses the unfolding of the Cuban missile crisis in the context of the 17th General Assembly of the UN and shows that, contrary to earlier accounts, U Thant was responding to pressures from the non-aligned and the British in his attempts to handle the crisis.

Prime Minister and President: Harold Macmillan’s accounts of the Cuban missile crisis

This chapter analyses the successive ways in which Macmillan re-wrote his experiences of the Cuban missile crisis and in the process sought to re-configure the memory of the event in Britain.

Les Flottes de combat en... (Paris)

Variante(s) de titre : Fighting fleets

[Les Flottes de combat en...]

1914.

L'Imprimerie au combat : organe de la Résistance

1944/04 (N4).