In vivo/in vitro pharmacokinetic and pharmacodynamic study of spray-dried poly-(dl-lactic-co-glycolic) acid nanoparticles encapsulating rifampicin and isoniazid

Poly-(dl-lactic-co-glycolic) acid (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation spray-drying technique and coated with polyethylene glycol (PEG 1% v/v). The PLGA nanoparticles had a small size (229±7.6 to 382±23.9nm), uniform size distribution and positive zeta potentia...

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Bibliographic Details
Published in:International journal of pharmaceutics 2013-02, Vol.444 (1-2), p.10-17
Main Authors: Booysen, L.L.I.J., Kalombo, L., Brooks, E., Hansen, R., Gilliland, J., Gruppo, V., Lungenhofer, P., Semete-Makokotlela, B., Swai, H.S., Kotze, A.F., Lenaerts, A., du Plessis, L.H.
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antitubercular - administration & dosage
Antibiotics, Antitubercular - chemistry
Antibiotics, Antitubercular - pharmacokinetics
chemotherapy
Delayed-Action Preparations - administration & dosage
Delayed-Action Preparations - chemistry
Delayed-Action Preparations - pharmacokinetics
Drug Carriers - administration & dosage
Drug Carriers - chemistry
Drug Carriers - pharmacokinetics
Drug Compounding
drugs
emulsions
encapsulation
evaporation
Female
In vitro
In vivo
Isoniazid
Isoniazid - administration & dosage
Isoniazid - chemistry
Isoniazid - pharmacokinetics
Lactic Acid - chemistry
liver
lungs
Mice
Mice, Inbred BALB C
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
nanocapsules
nanoparticles
Nanoparticles - administration & dosage
Nanoparticles - chemistry
oral administration
Particle Size
PEG coated
Pharmacodynamic
Pharmacokinetic
pharmacokinetics
PLGA nanoparticles
polyethylene glycol
Polyglycolic Acid - chemistry
protein binding
Rifampicin
Rifampin - administration & dosage
Rifampin - chemistry
Rifampin - pharmacokinetics
solvents
spray drying
tuberculosis
zeta potential
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Summary:Poly-(dl-lactic-co-glycolic) acid (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation spray-drying technique and coated with polyethylene glycol (PEG 1% v/v). The PLGA nanoparticles had a small size (229±7.6 to 382±23.9nm), uniform size distribution and positive zeta potential (+12.45±4.53mV). In vitro/in vivo assays were performed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) performance of these nanoparticles following nanoencapsulation of the anti-tuberculosis drugs rifampicin (RIF) and isoniazid (INH). The results demonstrated the potential for the reduction in protein binding of these drugs by protection in the polymer core. Furthermore, in vitro efficacy was demonstrated using Mycobacterium tuberculosis (M. tb.) (strain H37Rv). Sustained drug release over seven days were observed for these drugs following once-off oral administration in mice with subsequent drug distribution of up to 10 days in the liver and lungs for RIF and INH, respectively. It was concluded by these studies combined with our previous reports that spray-dried PLGA nanoparticles demonstrate potential for the improvement of tuberculosis chemotherapy by nanoencapsulation of anti-tuberculosis drugs.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2013.01.038