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Abstract
The use of nanocarriers in drug delivery is a breakeven research and has received a clarion call in biomedicine globally. Herein, two newly nano-biomaterials: MCM-41 encapsulated quinine (MCM-41 ⊃ QN) (1) and 3-phenylpropyl silane functionalized MCM-41 loaded QN (pMCM-41 ⊃ QN) (2) were synthesized and well characterized. 1 and 2 along with our two already reported nano-antimalarial drugs (MCM-41 ⊃ ATS) (3) and 3-aminopropyl silane functionalized MCM-41 contained ATS (aMCM-41 ⊃ ATS) (4) were screened in vitro for their activity against P. falciparium W2 strain, cytotoxicity against BGM cells and in vivo for their activity against Plasmodium bergheiNK65. 1 has the highest antimalarial activity in vivo against P. berghei NK65, (ED50: < 0.0625 mg/kg body weight) and higher mean survival time compared to the other nano biomaterials or unencapsulated drugs at doses higher than 0.0625 mg/kg body weight. This encapsulation strategy of MCM-41 ⊃ QN (1) stands very useful and effective in delivering the drug to the target cells compared to other delivery systems and therefore, this encapsulated drug may be considered for rational drug design.
Highlights
Delivery of antimalarial drugs to their target site through innovative drug delivery system with the goal of overcoming emerging global resistant parasites has been one of the commitments of World Health Organization[1]
A sol-gel synthetic method previously reported for the parent silica MCM-41 and 3-aminopropyl silane functionalized MCM-41 was followed with slight modification to carry out the syntheses of the MCM-41 and 3-phenylpropyl silane functionalized silica[30] (Fig. 2, see the Supporting Information)
Three diffraction peaks of the MCM-41 nanosilica were observed at 2θ angle of 2.63°, 4.34° and 5.03° which can be indexed to (100), (110) and (200) planes associated with a p6mmhexagonal symmetry (Fig. S1), similar to report in literatures[31]
Summary
Delivery of antimalarial drugs to their target site through innovative drug delivery system with the goal of overcoming emerging global resistant parasites has been one of the commitments of World Health Organization[1]. The high incidence of malaria, being the most dreaded human parasitic disease in the tropic and sub-tropic countries and drug-resistance cum toxicity turned the disease into a problem of major health importance[5,6] Some of these drugs have short half lives in the blood, e.g. artesunate (ATS), thereby leading to the problem of recrudescence while some of them exert some adverse effects at their therapeutic doses[7], e.g. quinine (QN) Fig. 1. Nanoveschiles lipid compliance as a rationale drug design was recently used to derive the local and global organization of a multi-mega Dalton peptide-based nanaocarrier It renders a high molecular detail and at close-to physiological conditions[15]. Various types of polymeric vessels, liposomes, e.g. neutral multi-lamellar liposomes with cholesterol modifications as nanocarriers have been used as support to facilitate the release of many antimalarial drugs to the infected red blood cells[27] the release of ATS from the neutral liposomes had been influenced by the lipid content in the liposomal bilayer, liposome dimension and drug release kinetics[28]
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