Enhanced intestinal absorption of asenapine maleate by fabricating solid lipid nanoparticles using TPGS: elucidation of transport mechanism, permeability across Caco-2 cell line and
            <i>in vivo</i>
            pharmacokinetic studies

Patel, Manthan; Mundada, Veenu P; Sawant, Krutika

doi:10.1080/21691401.2018.1546186

Cited by 40 publications

(17 citation statements)

References 38 publications

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“…Further, the P app of PMX/DCK-OP increased significantly, by 3.16- and 10.6-fold of the values for PMX/DCK and PMX, respectively (Table 1). This may reflect micelle formation by PMX/DCK in the presence of Labrasol and P188, enhancing drug absorption via macropinocytosis and clathrin-and caveolae-mediated endocytosis [45,46]. Moreover, the enhanced permeability of the Caco-2 cell monolayer to the powder formulation may indicate Labrasol-induced inhibition of glucuronidation.…”

Section: Resultsmentioning

confidence: 99%

Anti-Angiogenic Effect of Orally Available Pemetrexed for Metronomic Chemotherapy

et al. 2019

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Metronomic chemotherapy (MCT) is defined as the frequent administration of low-dose chemotherapeutics, without long drug-free periods, with the exertion of antitumor activity exclusively through anti-angiogenic mechanisms. In this study, we have developed an orally available formulation of pemetrexed (PMX) for MCT. PMX was first complexed ionically with Nα-deoxycholyl-l-lysyl-methylester (DCK) as the permeation enhancer. This was followed by dispersion with poloxamer 188 and Labrasol to form the solid oral formulation of PMX (PMX/DCK-OP). PMX/DCK-OP exhibited a 10.6-fold increase in permeability across a Caco-2 cell monolayer compared to PMX alone. This resulted in a 70-fold increase in the oral bioavailability of PMX/DCK-OP in mice over oral PMX alone. In the A549 xenograft model, tumor volume was reduced by 51.1% in the PMX/DCK-OP treated group compared to only 32.8% in the maximum tolerated dose (MTD)-treated group. Furthermore, PMX/DCK-OP exhibited a significant anti-angiogenic effect on the A549 xenograft mice when compared to the MTD-treated group, as indicated by microvessel density quantification for CD-31. In addition, PMX/DCK-OP enhanced the release of an endogenous angiogenesis inhibitor, thrombospondin-1 (TSP-1), into both the blood circulation and the tumor microenvironment. Therefore, due to its oral route of administration, PMX/DCK-OP appears to be a better alternative to the conventional treatment of PMX.

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Section: Resultsmentioning

confidence: 99%

Anti-Angiogenic Effect of Orally Available Pemetrexed for Metronomic Chemotherapy

et al. 2019

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“…16) which may be due to surfactant coating. Hence, it proven that there is no cytotoxicity up to 125µg/ml [32].…”

Section: Cytotoxicity Test Using Caco-2 Cellsmentioning

confidence: 86%

Surface Modification of Optimized Asenapine Maleate Loaded Solid Lipid Nanoparticles Using Box-Behnken Design

Devi

Vidyavathi

Suryateja³

2021

JPRI

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Aim: The aim of the present study was to design and evaluate solid lipid nanoparticles of Asenapine maleate (<2% bioavailability) to enhance its oral bioavailability and surface modification for brain targeting. Methods: A modified solvent injection method was used to produce Asenapine maleate loaded solid lipid nanoparticles. A RSM 3-factor, 3-level Box-Behnken design was applied to study the effect of three independent variables, concentrations of lipid (A), drug (B) and surfactant (C) on three dependent variables, particles size (Y1), entrapment efficiency (Y2), and drug release (Y3). 3-D surface response plots were drawn and optimized formulation was selected based on desirability factor. Then it was coated with tween 80 for ease of permeability through blood brain barrier due to intact absorption of solid lipid nanoparticles. Results: The results of coated optimized formulation showed average particle size of 108.9 nm, entrapment efficiency of 78.62%, and in vitro drug release of 98.88±0.102% at 36 hr at pH 7.4. Morphologically, particles were almost spherical in shape with uniform size distribution. Targeting of coated optimized formulation to brain after oral administration was confirmed by fluorescence microscopy studies on male albino wistar strain rats. This research also envisaged that there is a >85% cell viability up to 125µg/ ml concentration of coated solid lipid nanoparticles by MTT assay. Conclusion: Thus, the current study successfully designed, developed an optimized SLN formulation of Asenapine maleate using a 3-factor, 3-level Box-Behnken design for brain targeting to treat Schizophrenia by bypassing the first pass metabolism with enhanced oral bioavailability.

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“…They reported a 50-fold improvement in the oral bioavailability of asenapine maleate in rats, compared with free drug. The plasmatic concentration of the drug significantly decreased when animals were pre-treated with cycloheximide, unveiling the contribution of lymphatic transport in the enhanced drug bioavailability [68].…”

Section: Enhancement Of Lymphatic Transportmentioning

confidence: 97%

“…paclitaxel or docetaxel [63][64][65][66], central nervous system drugs, e.g. lurasidone or asenapine [67,68], cardiovascular drugs, e.g. carvedilol or cilnidipine [69,70], or antiviral drugs [71].…”

Section: Solid Lipid Nanoparticlesmentioning

confidence: 99%

Current approaches in lipid-based nanocarriers for oral drug delivery

Plaza-Oliver

Santander-Ortega

Lozano

2021

Drug Deliv. and Transl. Res.

113

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Graphical abstract Lipid-based nanocarriers have gained much interest as carriers of drugs with poor oral bioavailability because of their remarkable advantages like low toxicity, affordable scale-up manufacture, strong biocompatibility or high drug loading efficiency. The potential of these nanocarriers lies in their ability to improve the gastrointestinal stability, solubility and permeability of their cargo drugs. However, achieving efficient oral drug delivery through lipid-based nanocarriers is a challenging task, since they encounter multiple physicochemical barriers along the gastrointestinal tract, e.g. the gastric acidic content, the intestinal mucus layer or the enzymatic degradation, that they must surmount to reach their target. These limitations may be turned into opportunities through a rational design of lipid-based nanocarriers. For that purpose, this review focuses on the main challenges of the oral route indicating the strategies undertaken for lipid-based nanocarriers in order to overcome them. Understanding their shortcomings and identifying their strengths will determine the future clinical success of lipid-based nanocarriers.

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Enhanced intestinal absorption of asenapine maleate by fabricating solid lipid nanoparticles using TPGS: elucidation of transport mechanism, permeability across Caco-2 cell line and in vivo pharmacokinetic studies

Cited by 40 publications

References 38 publications

Anti-Angiogenic Effect of Orally Available Pemetrexed for Metronomic Chemotherapy

Anti-Angiogenic Effect of Orally Available Pemetrexed for Metronomic Chemotherapy

Surface Modification of Optimized Asenapine Maleate Loaded Solid Lipid Nanoparticles Using Box-Behnken Design

Current approaches in lipid-based nanocarriers for oral drug delivery

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