Abstract |
The main objective of this investigation was to establish the pharmacokinetics profile and in vivo chemosuppressive activities of cryptolepine hydrochloride-loaded gelatine nanoparticles (CHN) designed for parenteral administration for the treatment of malaria in comparison to the drug free in solution (CHS). Single-dose pharmacokinetics was investigated in Wistar rats by administering CHN or CHS (equivalent to 10 mg/kg of drug) by IV bolus injection via the lateral tail vein. The drug concentration in plasma was monitored over a 24-h period following administration. Chemosuppressive activity was investigated in Wistar rats challenged with P berghei parasites. Animals were given a daily dose of either CHN or CHS, equivalent to 2.5-100 mg/kg by intraperitoneal injection. The level of parasitaemia was determined by light microscopy by examining Giemsa-stained thin blood smears prepared from the tail end on day four of infection. It was found that CHN attained a higher (4.5-folds) area under the curve (AUC (0-24)) compared to CHS. CHS however produced a higher volume of distribution (4-folds). Distribution and elimination rates were higher with CHS which resulted in a lower (11.7 h) elimination half-life compared to that of CHN (21.85 h). The superior pharmacokinetic profile of CHN translated into superior chemosuppressive activity at all dose levels relative to CHS. As a conclusion, loading cryptolepine hydrochloride into gelatine nanoparticles improved both pharmacokinetics and in vivo antiplasmodial activity of the compound with the highest chemosuppression (97.89 ± 3.10) produced by 100 mg/kg of CHN.
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Authors | N Kuntworbe, M Ofori, P Addo, M Tingle, R Al-Kassas |
Journal | Acta tropica
(Acta Trop)
Vol. 127
Issue 3
Pg. 165-73
(Sep 2013)
ISSN: 1873-6254 [Electronic] Netherlands |
PMID | 23643517
(Publication Type: Journal Article)
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Copyright | Copyright © 2013 Elsevier B.V. All rights reserved. |
Chemical References |
- Antimalarials
- Indole Alkaloids
- Quinolines
- cryptolepine
- Gelatin
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Topics |
- Animals
- Antimalarials
(chemistry, pharmacokinetics, pharmacology)
- Area Under Curve
- Brain Chemistry
- Drug Administration Routes
- Gelatin
(chemistry)
- Indole Alkaloids
(chemistry, pharmacokinetics, pharmacology)
- Kidney
(chemistry)
- Liver
(chemistry)
- Lung
(chemistry)
- Malaria
- Male
- Molecular Structure
- Myocardium
(chemistry)
- Nanostructures
(chemistry)
- Quinolines
(chemistry, pharmacokinetics, pharmacology)
- Rats
- Rats, Wistar
- Spleen
(chemistry)
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