Nanoparticulation improves bioavailability of Erlotinib

Yang, Kyung Mi; Shin, In Chul; Park, Joo Won; Kim, Kab-Sig; Kim, Dae Kyong; Park, Kyungmoon; Kim, Kunhong

doi:10.1080/03639045.2017.1326931

Cited by 26 publications

(10 citation statements)

References 31 publications

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“…B). In addition, NUFS‐sErt has shown an improved solubility and an increased dissolution rate compared with erlotinib in a previous pharmacokinetic (PK) study in dogs, although the formulation of the drug was different in that report due to different administration route requirements (Yang et al ., ).…”

Section: Resultsmentioning

confidence: 97%

“…This approach prevents the undesirable side effects of other commonly used excipients and can produce nano-sized particles in large quantities. Erlotinib has a very low solubility at neutral pH, largely preventing its delivery by injection (Yang et al, 2017). We have however applied our NUFS TM technology to produce a water-soluble, nano-particulated erlotinib, NUFS-sErt, which showed a comparable efficacy to its parent compound against EGFR-mutant lung cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Nano-particulation using fat and supercritical fluid-sErt had been prepared using NUFS TM technology (nanoparticulation using fat and supercritical fluid) from Bio-Synectics as part of a previous study (Yang et al, 2017). One gram of erlotinib free base, 0.2 g of poloxamer 188, and 10 g of myristyl alcohol were mixed and clearly melted at 130°C.…”

Section: Preparation Of Nufs-sert Powdermentioning

confidence: 99%

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Efficacy of nano‐particulated, water‐soluble erlotinib against intracranial metastases of EGFR‐mutant lung cancer

et al. 2018

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Central nervous system (CNS) metastasis is one of the serious complications of epidermal growth factor receptor (EGFR)‐mutant lung cancer, which arises due to poor penetration of the brain–blood barrier by EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). Although osimertinib, a third‐generation EGFR‐TKI, has efficacy against CNS metastases, further treatment modalities are still needed as some of these lesions do not respond to osimertinib, or undergo progression after an initial response to this drug if radiotherapy has already been conducted. Here, we investigated the efficacy of water‐soluble erlotinib (NUFS‐sErt) against these metastases. This agent was synthesized using a nano‐particulation platform technology utilizing fat and supercritical fluid (NUFS™) to resolve the low solubility problem that typically prevents the creation of injectable forms of EGFR‐TKIs. The average NUFS‐sErt particle size was 236.4 nm, and it showed time‐dependent dissolution in culture media. The effects of NUFS‐sErt were similar to those of conventional erlotinib in terms of inhibiting the proliferation of EGFR‐mutant lung cancer cells and suppressing EGFR signaling. In an intraperitoneal xenograft model of HCC827 cells, intraperitoneal administration of NUFS‐sErt produced a dose‐dependent inhibition of tumor growth and enhanced survival rate. Notably, the injection of NUFS‐sErt into the brain ventricle caused significant tumor growth inhibition in an intracranial xenograft model. Hence, our current findings indicate that NUFS‐sErt is a novel, water‐soluble form of erlotinib that can be administered using intraventricular or intrathecal injections. The target cases would be patients with a progressive CNS metastasis and no other therapeutic options. This drug could also be given intravenously to patients with swallowing difficulties or an inability to ingest due to a medical condition.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Nufs-sert Powdermentioning

confidence: 99%

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Efficacy of nano‐particulated, water‐soluble erlotinib against intracranial metastases of EGFR‐mutant lung cancer

et al. 2018

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“…kinase inhibitors (TKIs) that have exhibited clinical benefit in treating NSCLC (6,7). Erlotinib treatment prolonged the progression-free survival of NSCLC patients, who harbor EGFR exon 19 deletion or L858R mutations (EGFR Mut+ NSCLC) (8). However, almost all tumors eventually develop acquired resistance to the treatment, with 50% of the patients developing EGFR T790M resistance mutations (9).…”

Section: Combination Of Huanglian Jiedu Decoction and Erlotinib Delaymentioning

confidence: 99%

Combination of Huanglian Jiedu Decoction and erlotinib delays growth and improves sensitivity of EGFR‑mutated NSCLC cells in vitro and in vivo via STAT3/Bcl‑2 signaling

et al. 2020

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Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in the treatment of non-small cell lung cancer (NSCLC). However, erlotinib resistance leads to high mortality in patients with NSCLC, while the activation of STAT3 is closely related to erlotinib resistance. Studies have shown that the main components of Huanglian Jiedu Decoction (HJD) have antitumor effects. Therefore, the anticancer effect of HJD combined with erlotinib on NSCLC cells was investigated. The NSCLC HCC827, HCC827ER, and H1975 cell lines as well as xenograft nude mice were selected as models to study the effects of HJD. The proapoptotic effects of HJD were examined by CCK-8 and apoptosis assays. ELISA, immunostaining, and western blot analysis were also performed. HJD considerably enhanced the anticancer effect of erlotinib in both EGFR-TKI-resistant and -sensitive NSCLC cells. HJD promoted erlotinib-induced apoptosis and caspase 3 activity. The co-treatment also inhibited the expression of Bcl-XL, Bcl-2, and p-STAT3. In addition, siSTAT3 had similar functions with HJD. In particular, the apoptotic rates of erlotinib-stimulated HCC827, HCC827ER, and H1975 cells were enhanced by transfecting siSTAT3. Furthermore, overexpression of STAT3 significantly inhibited HJD-mediated erlotinib sensitization. The combined use of HJD with erlotinib significantly reduced tumor growth in erlotinib-resistant HCC827ER and H1975 ×enografts, induced caspase 3, and inhibited Ki67, STAT3, and Bcl-2 expression. HJD significantly alleviated erlotinib resistance by regulating the STAT3/Bcl-2 signaling pathway, which is a promising method to overcome the EGFR-TKI resistance of NSCLC.

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“…Erlotinib hydrochloride (ETB) is a USFDA-approved drug (previously known as OSI-774 and CP-358774), for NSCLC [8]. ETB chemically is [6,7-bis(2-methoxy-ethoxy)-quinazolin-4-yl]-(3ethynylphenyl) amine hydrochloride, a human epidermal growth factor type/epidermal growth factor receptor (HERl/ EGFR) tyrosine kinase inhibitor [9][10][11]. It promotes cell cycle arrest, apoptosis leading to inhibition of angiogenesis and cell invasion by binding to the intracellular tyrosine kinase domain of EGFR, thereby inhibiting receptor autophosphorylation and blocking downstream signal transduction.…”

Section: Introductionmentioning

confidence: 99%

Extended release delivery of erlotinib glutathione nanosponge for targeting lung cancer

Momin

Zaheer

Zainuddin

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Systemic and uncontrolled administration of erlotinib hydrochloride (ETB) is associated with severe toxicity. A novel targeted and extended release nanosponge (NS) was synthesized from glutathione (GHS) by a one-step reaction between β-cyclodextrin and pyromellitic dianhydride at room temperature for delivery of ETB in lung cancer. Characterization studies were performed using sophisticated instruments. In-vitro release study was performed in the presence of incremental concentrations of GHS which was analyzed using HPLC. Cell cytotoxicity study was evaluated on human lung cancer (A549) cell lines. In-vivo tumour inhibition and biodistribution of ETB-loaded GHS-NS (ETB-NS) were performed on BALB/c mice. NS obtained was spherical, size 212 ± 2.45 nm and high drug entrapment (92.34 ± 5.31%) (p < .001). In-vitro extended drug release (76.89 ± 0.1% release at 168 h), which was directly proportional to the concentration of GHS, demonstrated tumour targeting. There was enhanced in-vitro cytotoxicity and 97.5% inhibition in tumour growth on administering NS when compared to plain ETB (48% inhibition) indicating targeting of NS to the tumour site. Biodistribution study and in-vivo tumour growth inhibition study revealed drug release to the cancerous cell, thus preventing unnecessary drug exposure. ETB-NS exhibits extended drug release proportional to the external GSH concentration.

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Nanoparticulation improves bioavailability of Erlotinib

Cited by 26 publications

References 31 publications

Efficacy of nano‐particulated, water‐soluble erlotinib against intracranial metastases of EGFR‐mutant lung cancer

Efficacy of nano‐particulated, water‐soluble erlotinib against intracranial metastases of EGFR‐mutant lung cancer

Combination of Huanglian Jiedu Decoction and erlotinib delays growth and improves sensitivity of EGFR‑mutated NSCLC cells in vitro and in vivo via STAT3/Bcl‑2 signaling

Extended release delivery of erlotinib glutathione nanosponge for targeting lung cancer

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