Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation

Pangeni, Rudra; Choi, Sang Won; Jeon, Ok-Cheol; Byun, Youngro; Park, Jin Woo

doi:10.2147/ijn.s121114

Cited by 62 publications

(35 citation statements)

References 58 publications

(47 reference statements)

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“…DOCA is known to modulate or increase intestinal paracellular permeability via epithelial growth factor receptor (EGFR) auto-phosphorylation, occludin dephosphorylation, and rearrangement at the tight junction level. 34,51 It was also reported that P188 can change the lateral packing density of membranes by insertion into the lipid layers. 52…”

Section: Partition Coefficient and Membrane Permeabilitymentioning

confidence: 98%

“…The in vitro intestinal membrane permeabilities of free PMX, HP-beta-CD/PMX, PMX/DCK, HP-beta-CD/PMX/DCK, HP-beta-CD/PMX/DCK/P188, and HP-beta-CD/PMX/DCK/ P188-NE were evaluated using a parallel artificial membrane permeability assay (PAMPA; BD Biosciences, San Jose, CA, USA) as described previously. 34 Donor samples were prepared by the dilution of free PMX, PMX/DCK complexes, or HP-beta-CD/PMX/DCK/P188-NE with PBS (pH 6.8) at a concentration equivalent to 200 μg/mL PMX. Then, 200 μL of sample solution was added to each well of the donor plate, and 300 μL of PBS (pH 6.8) was added to each well of the acceptor plate.…”

Section: In Vitro Artificial Intestinal Membrane Permeabilitymentioning

confidence: 99%

“…Furthermore, the formulation of multiple water-in-oil-in-water (w/o/w) nanoemulsions by the incorporation of an amphiphilic oxaliplatin/DCK complex significantly enhanced the oral absorption and tumor growth inhibition of oxaliplatin. 34 Thus, our approach of preparing ion-pairing complex and multiple nanoemulsions can effectively improve oral drug absorption with a minimal quantity of enhancer compared with conventional penetration enhancers.…”

mentioning

confidence: 99%

“…Preparation and characterization of hP-beta-cD/PMX/DcK/P188 complex DCK was synthesized by the conjugation of DOCA with a positively charged lysine and used as an oral absorption enhancer as previously described. 34 The ionic complex formation of PMX and DCK (PMX/DCK) was prepared to enhance the intestinal membrane permeability of PMX ( Figure 1A). In addition, HP-beta-CD and P188 were added for the purpose of avoiding the aggregation of PMX/DCK complex during preparation as well as improving its re-dispersion in aqueous medium.…”

mentioning

confidence: 99%

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Enhanced oral absorption of pemetrexed by ion-pairing complex formation with deoxycholic acid derivative and multiple nanoemulsion formulations: preparation, characterization, and in vivo oral bioavailability and anticancer effect

Pangeni

Choi

Panthi

et al. 2018

IJN

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ObjectiveThe current study sought to design an oral delivery system of pemetrexed (PMX), a multitargeted antifolate antimetabolite, by enhancing its intestinal membrane permeability.Materials and methodsPMX was ionically complexed with a permeation enhancer such as Nα-deoxycholyl-l-lysyl-methylester (DCK) and prepared as an amorphous solid dispersion by mixing with dispersants such as 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and poloxamer 188 (P188), forming an HP-beta-CD/PMX/DCK/P188; the complex was incorporated into multiple water-in-oil-in-water nanoemulsions in a supersaturated state (HP-beta-CD/PMX/DCK/P188-NE).ResultsAfter complex formation, the partition coefficient and in vitro membrane permeability of PMX were markedly increased, but it showed similar cytotoxic and inhibitory effects on cancer cell proliferation/migration. Furthermore, the intestinal membrane permeability and epithelial cell uptake of PMX were synergistically improved after HP-beta-CD/PMX/DCK/P188 was incorporated into a nanoemulsion with a size of 14.5±0.45 nm. The in vitro permeability of HP-beta-CD/PMX/DCK/P188-NE across a Caco-2 cell monolayer was 9.82-fold greater than that of free PMX, which might be attributable to the partitioning of PMX to the epithelial cells being facilitated via specific interaction of DCK with bile acid transporters, as well as the enhanced lipophilicity accompanied by surfactant-induced changes in the intestinal membrane structure and fluidity. Therefore, the oral bioavailability of HP-beta-CD/PMX/DCK/P188-NE in rats was evaluated as 26.8%±2.98% which was 223% higher than that of oral PMX. Moreover, oral HP-beta-CD/PMX/DCK/P188-NE significantly suppressed tumor growth in Lewis lung carcinoma cell-bearing mice, and the tumor volume was maximally inhibited by 61% compared with that in the control group.ConclusionThese results imply that HP-beta-CD/PMX/DCK/P188-NE is an effective and promising delivery system for enhancing the oral absorption of PMX. Thus, there is the potential for new medical applications, including applications in metronomic cancer treatment.

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Section: Partition Coefficient and Membrane Permeabilitymentioning

confidence: 98%

Section: In Vitro Artificial Intestinal Membrane Permeabilitymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Enhanced oral absorption of pemetrexed by ion-pairing complex formation with deoxycholic acid derivative and multiple nanoemulsion formulations: preparation, characterization, and in vivo oral bioavailability and anticancer effect

Pangeni

Choi

Panthi

et al. 2018

IJN

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“…Clinically, Oxa is often utilized as a first-line chemotherapy strategy in combination with 5FU for treatment of advanced colorectal cancer. 66 Presently, both drugs are administered by the intravenous route and exhibit poor oral bioavailability. However, a recent study aimed to develop an oral delivery system for Oxa and 5FU.…”

Section: Neoplasmsmentioning

confidence: 99%

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

Kermanizadeh¹,

Powell²,

Stone³

2018

IJN

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The use of nanoparticles as a means of targeted delivery of therapeutics and imaging agents could greatly enhance the transport of biologically active contents to specific target tissues, while avoiding or reducing potentially undesired side effects. Generally speaking, the oral route of administration is associated with good patient compliance, as it is convenient, economical, noninvasive, and does not require special training. Here, we review the progress of the utilization of nanodelivery-system carriers or stabilized solid-drug nanoparticles following oral administration, with particular attention on toxicological data. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge to human scenarios highlighted. Additionally, issues associated with administration of drugs via the oral route are underlined, while strategies utilized to overcome these are highlighted. This review aims to offer a balanced overview of strategies currently being used in the application of nanosize constructs for oral medical applications.

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A Review of the Current State of Nanomedicines for Targeting and Treatment of Cancers: Achievements and Future Challenges

Kermanizadeh

Jacobsen

Murphy

et al. 2020

Advanced Therapeutics

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The design and utilization of nanomedicines offers great potential for treating various diseases including cancers. Current challenges with traditional cancer treatment strategies include but are not limited to lack of specific targeting, overt systemic toxicity and low efficacy. The use of nanomaterials show particular promise as candidates for cancer treatment due to their high surface to volume ratio and tuneable size, shape, and surface chemistry, which in combination, allow for improved tumor targeting and enhanced therapeutic efficacy. The scrutinization of the literature demonstrates the potential of nanosized carrier systems over traditional approaches (at the molecular level) for specific targeting of the tumors. Despite the great promise showing in preclinical studies, the number of nanomedicines reaching clinical testing is still very low. This review attempts to address this issue by using a weight of evidence approach to the different strategies for use of nanomedicines in combating cancer, as well as highlighting a number of areas that the field of nanomedicines is clearly lagging behind in, as compared to conventional drug discovery and development. It is hoped that the recommendations in this review will allow for better translation of nanomedicines reaching clinical trials.

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Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation

Cited by 62 publications

References 58 publications

Enhanced oral absorption of pemetrexed by ion-pairing complex formation with deoxycholic acid derivative and multiple nanoemulsion formulations: preparation, characterization, and in vivo oral bioavailability and anticancer effect

Enhanced oral absorption of pemetrexed by ion-pairing complex formation with deoxycholic acid derivative and multiple nanoemulsion formulations: preparation, characterization, and in vivo oral bioavailability and anticancer effect

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

A Review of the Current State of Nanomedicines for Targeting and Treatment of Cancers: Achievements and Future Challenges

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