In Vivo
 Evaluation of Paclitaxel-Loaded Lipid Nanocapsules After Intravenous and Oral Administration on Resistant Tumor

Groo, Anne-Claire; Bossière, M; Trichard, Laury; Legras, Pierre; Benoı̂t, Jean-Pierre; Lagarce, Frédéric

doi:10.2217/nnm.14.124

Cited by 40 publications

(21 citation statements)

References 54 publications

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“…Combined data of the preclinical and the pharmacokinetic studies tend to indicate that the antischistosomal activity enhancement of MFS by LNCs most probably involved the relatively stable MFS-LNCs and accordingly was not solely dependent on systemic exposure to molecular MFS. Such findings corroborated those of previous studies in pointing out that classical drug PK/PD relationships should be considered prudently for oral nanomedicines [ 62 , 63 ]. In fact, the efficacy of paclitaxel against resistant tumors was shown recently to depend on the structural integrity of nanomedicines rather than the AUC post oral absorption [ 63 ], accounting for the lack of PD/PK correlations.…”

Section: Discussionsupporting

confidence: 90%

“…Such findings corroborated those of previous studies in pointing out that classical drug PK/PD relationships should be considered prudently for oral nanomedicines [ 62 , 63 ]. In fact, the efficacy of paclitaxel against resistant tumors was shown recently to depend on the structural integrity of nanomedicines rather than the AUC post oral absorption [ 63 ], accounting for the lack of PD/PK correlations. Further, oral nanomedicines may increase efficacy by targeting the sites of pathology.…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2015

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

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

et al. 2015

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“…Currently, the PEGylation of LNCs induced by Kolliphor ® HS15 is insufficient and the MRT of decitabine (C12) 2 -loaded LNCs has to be enhanced by the PEGylation of LNCs with a larger PEG chain. 48 Indeed, Groo et al 49 have already demonstrated that such PEGylation of LNCs enhances the MRT by a factor of 1.5.…”

Section: Discussionmentioning

confidence: 99%

Di-O-lauroyl-decitabine-lipid nanocapsules: toward extending decitabine activity

Briot¹,

Roger²,

Haidar³

et al. 2019

IJN

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Background: Acute myeloid leukemia mainly affects adult patients. Complete remission for patients younger than 60 years, who are candidates for standard induction therapy, is achieved in 60%-80% of cases. However, the prognosis is still poor for older patients, who are unfit for intensive chemotherapy, and only a few therapies are available. Hypomethylating agents, such as decitabine, are approved for such patients. The current dosing regimen consists of one administration per day, for 5 days, each 4 weeks. Methods: Here, we present the synthesis of a decitabine prodrug, combined with its encapsulation into a lipid-based nanocapsule formulation. Decitabine (C12) 2 was synthetized, then loaded into nanocapsules. Its stability in phosphate buffer ans human plasma was checked. Its activity was evaluated by Cell proliferation assays and cell-cycle analysis on human erythroleukemia cells. Then its pharmacokinetics was determined on a rat model. Results: Decitabine (C12) 2 was obtained with a yield of 50%. Drug loading into nanocarriers of 27.45±0.05 nm was 5.8±0.5 mg/mL. The stability of decitabine was improved and its activity on leukemia cells was not altered. Finally, pharmacokinetics studies showed a prolonged mean residence time of the drug. Conclusion: Decitabine (C12) 2 as a prodrug showed high encapsulation efficiency, a good stability in plasma with no impact on its activity on leukemia cells and improved pharmacokinetics.

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“…42 Moreover, LNCs are a potential peptide drug carrier for oral delivery as they have been shown to be stable in gastrointestinal-simulated media, 43 have demonstrated their ability to cross intestinal mucus, 44 and show improved bioavailability. 45 Moreover, the free surface of AMP-encapsulating nanoparticulate systems could allow their decoration or modification to improve their delivery to intended sites. 46 Peptide delivery still presents many challenges, but peptide-loaded RM-LNCs show great promise for various applications.…”

Section: Protease Degradation Assaymentioning

confidence: 99%

Reverse micelle-lipid nanocapsules: a novel strategy for drug delivery of the plectasin derivate AP138 antimicrobial peptide

Groo

Matougui

Umerska

et al. 2018

IJN

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IntroductionResistance to traditional antibiotics is an increasingly serious problem. Antimicrobial peptides (AMPs) have emerged as a new therapeutic class with great potential against infectious diseases, as they are less prone to induce resistance. Nanotechnology-based delivery strategies can improve the efficiency and stability of AMPs, particularly against proteolytic degradation. Lipid nanocapsules (LNCs) are a new generation of biomimetic nanocarriers and were used in this study to deliver peptides.MethodsAMP-loaded reverse micelles (RM) were developed and incorpo rated into LNCs by the phase inversion process and the antimicrobial activity of the AMPs-loaded LNC was evaluated by the minimum inhibitory concentration method. We studied the activity of AMP solutions and AMP-loaded LNCs against Gram-positive and Gram-negative bacterial strains and then evaluated the encapsulation of a new cationic AMP called AP138. Finally, we analyzed the effect of enzymatic attack on AP138 and AP138-RM-LNCs after incubation with trypsin.ResultsAP138 was efficiently encapsulated in the LNCs (encapsulation efficiency = 97.8% at a drug loading of 0.151%), resulting in protection against degradation by proteases and the preservation of antimicrobial activity against Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus.ConclusionThis study shows that RM-LNCs are an excellent candidate system to deliver AMPs.

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In Vivo Evaluation of Paclitaxel-Loaded Lipid Nanocapsules After Intravenous and Oral Administration on Resistant Tumor

Abstract: This study highlights the importance of efficacy studies paired to pharmacokinetic studies for nanomedicines.

Cited by 40 publications

References 54 publications

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

<p>Di-<em>O</em>-lauroyl-decitabine-lipid nanocapsules: toward extending decitabine activity</p>

Reverse micelle-lipid nanocapsules: a novel strategy for drug delivery of the plectasin derivate AP138 antimicrobial peptide

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