Tumour targeting: biological factors and formulation advances in injectable lipid nanoparticles.

Cancer chemotherapeutic agents are often administered systemically. Following systemic administration, numerous biological factors associated with the tumours influence the delivery of the drugs to the tumours. These factors have been extensively studied for the last 2 decades. The influence of these biological factors has brought about a drastic change in the design of drug delivery systems to solid tumours. This review discusses the various biological factors influencing drug delivery to tumours and the subsequent development of injectable delivery systems (i.e., lipid-based nanoparticles (SLNs)) for adequate delivery of drug to solid tumours.

The Hayek oscillator. Nomograms for tidal volume and minute ventilation using external high frequency oscillation.

The Hayek Oscillator is a recent development in external high frequency ventilation and is a useful mode of ventilatory support during anaesthesia, in chronic respiratory failure and weaning in intensive care. The Hayek Oscillator is new and its application is growing, as are the number of patients who have benefited from its use. However, there are no clear guidelines on how best to adjust the oscillator to achieve optimum ventilation. A simple method of predicting changes in tidal volume and minute ventilation following adjustment would make the oscillator more useful. We present nomograms for tidal volume, minute ventilation and effective alveolar ventilation when the three variables, oscillator frequency, mean chamber pressure and peak-to-trough pressure span were adjusted. The frequency-tidal volume relationship was unaffected by a mean chamber pressure of 0, -5, -10 cmH2O, but altered with changes in peak-to-trough pressure span. We have also determined the effect of increasing negative extrathoracic pressure on functional residual capacity. The relationship between tidal volume and frequency was non-linear and related to the peak-to-trough pressure span. Mean functional residual capacity significantly increased from 2.25 l (SEM 0.10) without the cuirass at rest to 2.61 l (SEM 0.14) at -10 cmH2O (p < 0.05; n = 5) and 2.47 (SEM 0.12) at -20 cmH2O of mean chamber pressure. Vital capacity was unchanged by increasing extrathoracic pressure as was total lung capacity.

Influence of protein flexibility on the redox potential of rubredoxin: energy minimization studies.

A theoretical investigation of the protein contribution to the redox potential of the iron-sulfur protein rubredoxin is presented. Structures of the oxidized and reduced forms of the protein were obtained by energy minimizing the oxidized crystal structure of Clostridium pasteurianum rubredoxin with appropriate charges and parameters. By including 102 crystal waters, structures close to the original crystal structure were obtained (rms difference of 1.16 A), even with extensive minimization, thus allowing accurate calculations of comparative energies. Our calculations indicate an energy change of about -60 kcal/mol (2.58 eV) in the protein alone upon reduction. This energy change was due to both the change in charge of the redox site and the subsequent relaxation of the protein. An energy minimization procedure for the relaxation gives rms differences between the oxidized and reduced states of about 0.2 A. The changes were small and occurred in both the backbone and sidechain mainly near the Fe-S center but contributed about -16 kcal/mol (0.69 eV) to the total protein contribution. Although the neglect of certain effects such as electronic polarization may make the relaxation energies calculated an upper limit, the results indicate that protein relaxation contributes substantially to the redox potential.