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Drug Targeting to the Lung: Chemical and Biochemical Considerations
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Peter A. Crooks, Narsimha R. Penthala, Abeer M. Al-Ghananeem
Specific uptake by lung tissue is not restricted to lipophilic amines of the type previously mentioned. Certain antibiotics, such as leucomycin A3, show a high deposition in lung tissue at low concentration of drug (Kostenbauder and Sloneker 1990). A study (Suwa et al. 1989) on erythromycin derivatives, in which the 6′-, 11′-, 12′-, and 4′-hydroxyl groups were totally or partially replaced with O-methyl groups, indicated that these compounds, compared to the parent drug, exhibited a marked increase in lung tissue uptake (four to five times greater) after administration into the external jugular vein of rats (Figure 3.5). Of note, erythromycin also has a strongly basic nitrogen. It is interesting that such a significant structural change to the erythromycin molecule does not apparently result in a loss of anti-microbial activity. The tissue levels obtained were in the decreasing order: 6'-,11'-,12'-,4'-OCH3 EM >6'-,11'-,4'-OCH3 EM > 6'-,4'-OCH3 EM = 6'-,11'-OCH3 EM = 6'-OCH2CH3EM > 11'-OCH3 EM > EM. The most potent anti-microbial derivative was shown to be 6'-OCH3 EM. Some derivatives of steroidal drugs also exhibit better uptake in lung tissue than their parent compounds. Budesonide (Figure 3.6) is a glucocorticosteroid that has been used in inhalation therapy for many years (Clissold and Heel 1984). It possesses a 16α, 17α-acetal group that makes the molecule less polar and confers on the molecule better uptake properties in lung tissue. (Note: budesonide is used as a 1:1 mixture of the 22R- and 22S-epimers.) Budesonide is not metabolized in lung tissue and is slowly released from the lung to the systemic circulation. However, it is rapidly metabolized to the 23-hydroxylated 22S-epimer and 16α-hydroxyprednisolone, which is selectively formed from the 22R-epimer. The rapid inactivation of systemic budesonide by the liver minimizes the potential for systemic side effects (Edsbacker and Andersson 2004, Andersson et al. 1987, Ryrfeldt et al. 1984). In isolated lung perfusion studies, a difference in the distribution between lung tissue and perfusion medium for the two epimers of budesonide was found. Interestingly, the pharmacodynamically more potent 22R epimer showed an uptake in lung tissue that was 1.4 times higher than that of the 22S epimer. This property may be due to the fact that the 22R epimer is less water-soluble than the 22S epimer (Ryrfeldt et al. 1984).
Healing of the cancer tissues under the action of moving heat and non-local Caputo–Fabrizio heat transport
Published in Waves in Random and Complex Media, 2022
Sudip Mondal, Abhik Sur, Mridula Kanoria
A common approach to hyperthermia of the lung has been whole-body hyperthermia (WBH). The use of WBH for lung cancer can be justified in the cases of metastatic disease, but necessarily lacks lung-specificity. Some of the loco-regional electromagnetic approaches for heating the lung require invasive thermometry, as an example, the radiofrequency capacitive devices not only have shown to be clinically feasible to be selected for advanced lung cancers but also have had limited acceptance, for reasons of labor intensity and inadequate control and tailoring of heating patterns [15–17]. More recently, isolated lung perfusion with chemotherapy, to concentrate drug in the lungs, has also been shown to be clinically feasible for co-administration of heat to one or both lungs. Moreover, no such histological evidence of lung or tracheal thermal damage was found in WBH canine studies employing external heating and concomitant airway heating with . The only negative observation was a temporary reduction in tracheal mucociliary transport [18,19].