Parasite impairment by targeting Plasmodium-infected RBCs using glyceryl-dilaurate nanostructured lipid carriers

Jain, Soniya A.; Basu, Himanish; Prabhu, Priyanka; Soni, Umangi; Joshi, Medha; Mathur, D.; Patravale, Vandana; Pathak, Sulabha; Sharma, Shobhona

doi:10.1016/j.biomaterials.2014.04.058

Cited by 30 publications

(13 citation statements)

References 53 publications

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“…The ARM-CP NLCs efficiently cleared malaria in infected mice at 20% of the therapeutic dose of both the actives (ie, achieving 80% dose reduction) in preclinical studies. 12 We also demonstrated prolonged drug release and reduced dosing frequency, factors vital to patient compliance (Jain et al, ''unpublished data''). In this article, we assessed the teratogenicity of the fabricated NLCs to confirm their suitability to treat malaria in pregnancy.…”

Section: Introductionmentioning

confidence: 70%

“…12 Thus, ARM–CP NLCs were designed to combat uncomplicated and severe malaria and were effective at significantly low doses in the murine model. 12 We therefore expected ARM–CP NLCs treatment to have minimal side effects and dose-related toxicity. The data obtained from this study indicated that drug-free NLCs did not exhibit any teratogenic effect, and observations made throughout the gestation period were comparable to the saline control group, clearly indicating that the nanoformulation itself was not teratogenic and was suitable for use in pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…Fabrication of NLCs was done as reported elsewhere. 12 The NLCs comprised of Capmul MCM and GDL as lipids, stabilized by a mixture of Tween 80 and Solutol HS 15. Briefly, ARM was solubilized in molten lipid mix to yield concentration of 37.5% wt/wt in the lipid load.…”

Section: Fabrication Characterization and Antimalarial Efficacy Of mentioning

confidence: 99%

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Teratogenicity of Artemether–Clindamycin Nanostructured Lipid Carriers in Rats

et al. 2016

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Currently, artemisinin-based combination therapy is considered the best option in the treatment of malaria. However, toxicity of artemisinins limits their use in pregnancy. In the absence of sufficient toxicity data, the World Health Organization recommends that artemisinins are not to be used in the first trimester of pregnancy and can be used only in second and third trimesters, when other treatments are not available. We have recently observed that drugs loaded in nanolipid carriers are selectively taken up in Plasmodium-infected erythrocytes with a concomitant reduction in the dose required to cure animals. Thus, 20% of the therapeutic dose of artemether-clindamycin (ARM-CP) loaded in nanostructured lipid carriers (NLCs; mean particle size 55 ± 10 nm) resulted in complete parasite clearance and 100% survival of infected mice. Here, we investigate the teratogenicity of this formulation in rodents (dosing on alternate days from 6th day to 18th day of gestation; 12-15 animals/group). The teratogenicity of drug-free NLCs and artesunate-clindamycin (ARS-CP) solution was also evaluated. We found that the therapeutic dose of ARS-CP caused fetal resorptions (87.5% resorptions in 8 litters), suggesting its unsuitability for use in pregnancy. Artesunate-clindamycin NLCs at therapeutic doses also resulted in ∼90% fetal resorptions in 10 litters examined. However, postimplantation losses or fetal malformations were not observed at the dose of ARM-CP NLCs that was required for complete parasite clearance in preclinical trials (ie, 20% of the therapeutic dose). Our data suggest that the NLCs loaded with 20% of the therapeutic dose of ARM-CP may have potential in treating malaria during pregnancy.

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Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Teratogenicity of Artemether–Clindamycin Nanostructured Lipid Carriers in Rats

et al. 2016

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“…Optical trap studies demonstrated that GDL-NLCs restore the flexibility of the infected RBCs. The NLCs can entrap hydrophobic drugs and selectively target them to the iRBCs and hence may be a potent drug delivery carrier for the treatment of malaria [28].…”

Section: Nanostructured Lipid Carrier As a Nanocarriermentioning

confidence: 99%

Nanobiotechnological modules as molecular target tracker for the treatment and prevention of malaria: options and opportunity

Jain

Vishwakarma

Gautam

et al. 2020

Drug Deliv. and Transl. Res.

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Malaria is one of the major infectious diseases that remains a constant challenge to human being mainly due to the emergence of drug-resistant strains of parasite and also the availability of drugs, which are non-specific for their pharmacodynamic activity and known to be associated with multiple side effects. The disease has acquired endemic proportions in tropical countries where the hygienic conditions are not satisfactory while the environmental conditions favor the proliferation of parasite and its transmission, particularly through the female anopheles. It is obvious that to square up the problems, there is a need for designing and development of more effective drugs, which can combat the drug-resistant strains of the parasite. Molecular biology of the parasite and its homing into host cellular tropics provide multiple drug targets that could judiciously be considered for engineering and designing of new generation antimalarial drugs and also drug delivery systems. Though the recent reports document that against malaria parasite the vaccine could be developed, nevertheless, due to smart mutational change overs by the parasite, it is able to bypass the immune surveillance. The developed vaccine therefore failed to assure absolute protection against the malarial infection. In the conventional mode of treatment antimalarial drugs, the dose and dosage regimen that is followed at large crops up the contraindicative manifestations, and hence compromising the effective treatment. The emerging trends and new updates in contemporary biological sciences, material sciences, and drug delivery domain have enabled us with the availability of a multitude of mode and modules which could plunge upon the nanotechnology in particular to treat this challenging infection. The nanotechnology-based option may be tuned or customized as per the requirements to mark and target i.e. the infected RBCs, for targeted drug delivery.

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“…The advantages of incorporating anti-malarial agents in nanometre-sized drug delivery systems composed of pharmaceuticallyacceptable materials have been amply demonstrated (Gupta et al, 2007;Haas et al, 2009;Jain et al, 2014;Movellan et al, 2014;Nayak et al, 2010).…”

Section: Introductionmentioning

confidence: 99%