Ch

NH^^^OH CH, anionic derivative of carrier

drug

Figure 4 Design of chlorphentermine-drug conjugates for lung targeting.

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 [113]. A recent report [118] 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 increased in lung tissue uptake (four to five times greater) after administration into the external jugular vein of rats (Fig. 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 antimicrobial 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 antimicrobial 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 (Fig. 6) is a glucocorticosteroid that has been used in inhalation therapy for several years [119]. It possesses a 16a, 17a acetal group that makes the molecule less polar and confers on the molecule better uptake properties in lung tissue. (Note:

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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