RESUMO
Adding Fluosol-DA and carbogen breathing to treatment with various anticancer drugs can result in a significant enhancement of tumor growth delay compared to the drug and air breathing. The optimal conditions for tumor response depend upon the drug, oxygenation level and duration, and perfluorochemical emulsion dosage. In this study, representative chemotherapeutic agents from several classes were tested in a tumor growth delay assay in combination with various doses of Fluosol-DA under conditions of normal aeration, carbogen breathing either for 1-2 hours or 6 hours, or with hyperbaric 100% oxygen (3 atmospheres) breathing for 1 hour to determine whether the antitumor activity of these drugs would be improved.
Assuntos
Antineoplásicos/uso terapêutico , Dióxido de Carbono/administração & dosagem , Fluorocarbonos/administração & dosagem , Neoplasias/tratamento farmacológico , Oxigênio/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Combinação de Medicamentos/administração & dosagem , Fibrossarcoma/tratamento farmacológico , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Derivados de Hidroxietil Amido , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Camundongos , Camundongos Endogâmicos C3H , Camundongos Nus , Transplante de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Células Tumorais CultivadasRESUMO
The emulsion stability of total nutrient admixtures (TNAs) containing various ratios of amino acids (AA):carbohydrate (CHO):fat (FAT) was studied. Eight different TNA formulations were prepared in duplicate using AA supplied as 8.5% crystalline AA (FreAmine III), CHO supplied as 70% dextrose injection, and FAT supplied as 10 or 20% lipid emulsion (Soyacal). The eight formulations represented AA:CHO:FAT ratios (v:v:v) of 2:1:1, 1:1:1, 1:1:1/2, and 1:1:1/4, respectively, with each lipid concentration. TNAs also contained identical concentrations of electrolytes, trace elements, vitamins, and heparin. TNAs were stored at 4 degrees C for 14 days and then at ambient temperature (22-25 degrees C) for another four days. All TNAs were analyzed for gross visual appearance, pH, osmolality, and particle size and distribution on day 0 and periodically throughout the study period. Particle size was measured by photon-correlation spectrometry and negative-phase light microscopy. Visual examination revealed the presence of creaming in all TNAs, which could be dispersed by gentle agitation. The pH of each TNA decreased slightly during the study period, while the osmolality showed little variation. The mean diameter of particles in the TNAs remained close to that in the original lipid emulsions; 95% of all particles in the TNAs were less than 0.454 micron in diameter, which is within the size range of natural lipid particles or chylomicrons. Based on examination of particle size, each TNA formulation was stable for 18 days under the conditions of this study.