title: Pharmacokinetics and in vivo chemosuppressive activity studies on cryptolepine hydrochloride and cryptolepine hydrochloride-loaded gelatine nanoformulation designed for parenteral administration for the treatment of malaria.
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.
authors: School of Pharmacy, The University of Auckland, Auckland, New Zealand.
authors: N
authors: N
authors: Kuntworbe
authors: M
authors: M
authors: Ofori
authors: P
authors: P
authors: Addo
authors: M
authors: M
authors: Tingle
authors: R
authors: R
authors: Al-Kassas
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D001923:Brain Chemistry; D004333:Drug Administration Routes; D005780:Gelatin / Q000737:chemistry*; D026121:Indole Alkaloids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008288:Malaria; D008297:Male; D015394:Molecular Structure; D009206:Myocardium / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000737:chemistry
chemical_list: D000962:Antimalarials; D026121:Indole Alkaloids; D011804:Quinolines; C024015:cryptolepine; D005780:Gelatin
keywords: Chemosuppression; Cryptolepine hydrochloride; Nanoparticles; Pharmacokinetics