• Home
  • Search Results
  • Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

PloS one (2015-11-18)
Maha M Eissa, Riham M El-Moslemany, Alyaa A Ramadan, Eglal I Amer, Mervat Z El-Azzouni, Labiba K El-Khordagui
ABSTRACT

Miltefosine (MFS) is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD). This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs) as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%), good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs, allowing targeting via the oral route. From a clinical point of view, data suggest MFS-LNCs as a potential single dose oral nanomedicine for enhanced therapy of schistosomiasis mansoni and possibly other diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, 99.93%
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Sigma-Aldrich
Oleic acid, ≥99% (GC)
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, ≥98%
Sigma-Aldrich
Oleic acid, technical grade, 90%
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, for molecular biology, ≥99%
Sigma-Aldrich
Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)
Sigma-Aldrich
Oleic acid, suitable for cell culture, BioReagent
Sigma-Aldrich
L-Lysine monohydrochloride, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, BioXtra, ≥99%
Sigma-Aldrich
Methanol, Laboratory Reagent, ≥99.6%
Sigma-Aldrich
Decanoic acid, ≥98.0%
Sigma-Aldrich
Methanol, ACS spectrophotometric grade, ≥99.9%
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, BioUltra, for molecular biology, ≥99.0% (AT)
Sigma-Aldrich
Methanol, BioReagent, ≥99.93%
Sigma-Aldrich
Oleic acid, natural, FCC
Sigma-Aldrich
L-Lysine monohydrochloride, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
Methanol, Absolute - Acetone free
Sigma-Aldrich
Decanoic acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Sigma-Aldrich
Decanoic acid, natural, ≥98%, FCC, FG
Sigma-Aldrich
L-Lysine monohydrochloride, BioUltra, ≥99.5% (AT)
Sigma-Aldrich
Dihexadecyl phosphate
Sigma-Aldrich
Oleic acid, meets analytical specification of Ph, Eur., 65.0-88.0% (GC)
Supelco
Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Sigma-Aldrich
Methanol, NMR reference standard