Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Nanomaterials (Basel) ; 9(8)2019 Aug 15.
Article in English | MEDLINE | ID: mdl-31443150

ABSTRACT

Aiming to improve the treatment outcomes of current daily tuberculosis (TB) chemotherapy over several months, we investigated whether nanoencapsulation of existing drugs would allow decreasing the treatment frequency to weekly, thereby ultimately improving patient compliance. Nanoencapsulation of three first-line anti-TB drugs was achieved by a unique, scalable spray-drying technology forming free-flowing powders in the nanometer range with encapsulation efficiencies of 82, 75, and 62% respectively for rifampicin, pyrazinamide, and isoniazid. In a pre-clinical study on TB infected mice, we demonstrate that the encapsulated drugs, administered once weekly for nine weeks, showed comparable efficacy to daily treatment with free drugs over the same experimental period. Both treatment approaches had equivalent outcomes for resolution of inflammation associated with the infection of lungs and spleens. These results demonstrate how scalable technology could be used to manufacture nanoencapsulated drugs. The formulations may be used to reduce the oral dose frequency from daily to once weekly in order to treat uncomplicated TB.

2.
Int J Nanomedicine ; 10: 1493-503, 2015.
Article in English | MEDLINE | ID: mdl-25759576

ABSTRACT

Tafenoquine (TQ), a new synthetic analog of primaquine, has relatively poor bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. A microemulsion formulation of TQ (MTQ) with sizes <20 nm improved the solubility of TQ and enhanced the oral bioavailability from 55% to 99% in healthy mice (area under the curve 0 to infinity: 11,368±1,232 and 23,842±872 min·µmol/L) for reference TQ and MTQ, respectively. Average parasitemia in Plasmodium berghei-infected mice was four- to tenfold lower in the MTQ-treated group. In vitro antiplasmodial activities against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no change in half maximal inhibitory concentration, suggesting that the microemulsion did not affect the inherent activity of TQ. In a humanized mouse model of G6PD deficiency, we observed reduction in toxicity of TQ as delivered by MTQ at low but efficacious concentrations of TQ. We hereby report an enhancement in the solubility, bioavailibility, and efficacy of TQ against blood stages of Plasmodium parasites without a corresponding increase in toxicity.


Subject(s)
Aminoquinolines , Antimalarials , Erythrocytes/parasitology , Nanostructures , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Administration, Oral , Aminoquinolines/administration & dosage , Aminoquinolines/chemistry , Aminoquinolines/pharmacokinetics , Aminoquinolines/pharmacology , Animals , Antimalarials/administration & dosage , Antimalarials/chemistry , Antimalarials/pharmacokinetics , Antimalarials/pharmacology , Biological Availability , Humans , Malaria , Mice , Nanostructures/administration & dosage , Nanostructures/chemistry
SELECTION OF CITATIONS
SEARCH DETAIL
...