China
Africa
Explore chapters and articles related to this topic
Autologous Hematopoietic Stem Cell Transplantation for Crohn’s Disease
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Robert M. Craig, Richard K. Burt
Conventional therapy uses the most benign drugs first, adding drugs with more potential side effects later. Sulfasalazine or mesalamine products are first line therapy. 5-aminosalicylate (5-ASA) is the active pharmacologic ingredient.50,51 If this anti-inflammatory agent is not effective, metronidazole or other antibiotics can be tried. Metronidazole is particularly effective in patients with anorectal fistulas.52 Failure to promote improvement or a remission requires the institution of immunosuppressive agents or corticosteroids. Whereas corticosteroids are extremely effective in producing a remission in most patients, they have the side effects of osteoporosis, obesity, cutaneous changes, decreased resistance to infection, diabetes mellitus, and aseptic necrosis of the femoral head.50 Budesonide is a corticosteroid with a large first-pass metabolism in the liver and consequently less systemic effects from therapy. Studies have shown its equal efficacy to prednisone in Crohn’s ileitis and ileocolitis.53
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).
Metal organic frameworks: an effective application in drug delivery systems
Published in Inorganic and Nano-Metal Chemistry, 2022
Christine Jeyaseelan, Priyansh Jain, Deeya Soin, Deepshikha Gupta
MOFs have also found use in delivery of drugs for treating pulmonary diseases because of its property of deep lung penetration in addition to other advantageous properties like high porosity, better drug loading etc. UiO-66 based nanoparticles form good candidates for this purpose.[108] CD-MOF is also found to be a promising material for drugs of respiratory diseases.[106] Budesonide, a pulmonary disease relief drug, especially for asthma symptoms, was loaded on γ-cyclodextrin MOF (CD-MOF) to improve its delivery.[109] Another composite using Fe-MIL-100 (MOF) for carrying theophylline (a drug for asthma and chronic obstructive pulmonary disease) is also tested to be useful, nontoxic carrier.[110]