nystatin-a1 and Communicable-Diseases

From the point of view of pharmaceutical design, development of carrier system of antimicrobial agents with functional properties should be required. We introduced here the development-process of liposomal formulations of polyene macrolide antibiotics, amphotericin B (AmB) and nystatin as injectable dosage forms. Both development of the effective encapsulation method of these drugs in liposomes and investigation of the encapsulation mechanism and the molecular states of them are important to determine the optimum lipid composition for therapeutic uses. Enhanced encapsulation of these hydrophobic drugs, long-circulation in blood and high targetability are the required functional properties for the carrier system. Low encapsulation of AmB in liposomes has been overcome by the incorporation of polyethylene glycol-lipid derivatives, DSPE-PEG. Both the hydration with 9% sucrose solution and the complex formation between AmB and DSPE-PEG contribute not only to the enhanced encapsulation of AmB in liposomes but also to the stability and long-circulation properties in blood. Encapsulation mechanism and the molecular states of AmB in liposomes were also investigated by several methods. AmB-encapsulating PEG liposomes (PEG-L-AmB) with optimum lipid composition also showed reduced toxicity and higher therapeutic efficacy on murine model of pulmonary aspergillosis than that of conventionally used AmB formulations. Further enhanced therapeutic effects was observed by using AmB-encapsulating PEG immunoliposomes (34A-PEG-L-AmB) carrying monoclonal antibodies at the distal ends of the PEG chains. On the contrary to AmB, encapsulation characteristics of nystatin were apparently different from that of AmB, though the chemical structure is very similar. Self-association of nystatin with sterol-free lipid membrane dominantly influences on the encapsulation characteristics. Many experiments about the encapsulation of antimicrobial agents in liposomes have been demonstrated by many researchers, but there are not so much drugs developed for commercially used. Optimization of the formulation of functional drug-carrier system should be important for the practical uses.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Communicable Diseases; Drug Carriers; Drug Design; Liposomes; Lung; Nystatin; Phosphatidylethanolamines; Polyethylene Glycols; Solvents

Infections of children with malignant disease, especially of the lympho-reticular system, are characterized by their severity, with a high mortality, as a consequence of defective immunocompetence. According to the immunosurveillance theory, temporary immune defects could have even facilitated the malignant growth. The neoplastic disease itself contributes to the immunodeficiency by multiple mechanisms. The powerful cytostatic-cytocidal drugs reduce the immune response also, especially in the phases of bone marrow depression. Granulocytopenia shows the most significant correlation with the incidence of serious infections. The different forms of hospital infections have been reviewed and classified as 1. bacterial, fungal and, rarely, (but most dangerous) protozoal infections, 2. endogenous infections with the patient's own anaerobic intestinal flora and 3. viral infections. The perspectives of up-to-date chemotherapy and management of the immunodeficiency e.g. with leucocyte transfusions, and attempts to prevent infection are discussed.

Topics: Amphotericin B; Antineoplastic Agents; Bacterial Infections; Blood Transfusion; Child; Communicable Diseases; Cross Infection; Humans; Immunologic Surveillance; Immunosuppression Therapy; Leukocytes; Leukopenia; Miconazole; Mycoplasma Infections; Mycoses; Neoplasms; Nutrition Disorders; Nystatin; Patient Isolation; Protozoan Infections; Tetracyclines; Virus Diseases

Topics: Antifungal Agents; Candidiasis; Communicable Diseases; Humans; Nystatin

Topics: Amphotericin B; Candida albicans; Candidiasis; Chloramphenicol; Communicable Diseases; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Nystatin; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Tetracycline