Abstract
Background: Coadministration of rifampicin (RIF)/isoniazid (INH) is clinically recommended to improve the treatment of tuberculosis. Under gastric conditions, RIF undergoes fast hydrolysis (a pathway hastened by INH) and oral bioavailability loss.
Aim: We aimed to assess the chemical stabilization and the oral pharmacokinetics of RIF nanoencapsulated within poly(-caprolactone)-b-PEG-b-poly(-caprolactone) 'flower-like' polymeric micelles.
Materials and methods: The chemical stability of RIF was evaluated in vitro under acid conditions with and without INH, and the oral pharmacokinetics of RIF-loaded micelles in rats was compared with those of a suspension coded by the US Pharmacopeia.
Results: Nanoencapsulation decreased the degradation rate of RIF with respect to the free drug. Moreover, in vivo data showed a statistically significant increase of RIF oral bioavailability (up to 3.3-times) with respect to the free drug in the presence of INH.
Conclusion: Overall results highlight the potential of this nanotechnology platform to develop an extemporaneous liquid RIF/INH fixed-dose combination suitable for pediatric administration. Original submitted 6 April 2013; Revised submitted 7 August 201.
| Original language | English |
|---|---|
| Pages (from-to) | 1635-1650 |
| Number of pages | 16 |
| Journal | Nanomedicine |
| Volume | 9 |
| Issue number | 11 |
| DOIs | |
| State | Published - 1 Aug 2014 |
Keywords
- extemporaneous liquid rifampicin/isoniazid fixed-dose combination
- improved oral pharmacokinetics
- pediatric tuberculosis
- poly(-caprolactone)-b-PEG-b-poly(-caprolactone) 'flower-like' polymeric micelle
- rifampicin chemical stabilization
All Science Journal Classification (ASJC) codes
- Bioengineering
- Medicine (miscellaneous)
- Biomedical Engineering
- General Materials Science
