Enhanced absorption, and efficacy of oral self-assembled paclitaxel nanocochleates in multi-drug resistant colon cancer

Shanmugam, Thanigaivel; Joshi, Nitin; Ahamad, Nadim; Deshmukh, Atul; Banerjee, Rinti

doi:10.1016/j.ijpharm.2020.119482

Cited by 18 publications

(11 citation statements)

References 51 publications

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“…However, uptake of CPT particles eventually impeded when these cells were pre-exposed to a metabolic inhibitor (0.1% azide) or 4 °C temperature (inhibited cytoskeletal remodeling), which suggests that the uptake of CPT particles was mediated by an energy-dependent process of endocytosis (active process). In our previous study, we observed a similar trend of in vitro uptake of R6G-CPT particles by a colon cancer cell line (HCT-15) …”

Section: Resultssupporting

confidence: 72%

“…In this study, we have focused on both formulation and the clinical novelty. While there are a few reports that tested the oral delivery application of nanocochleates, , the aerosol-based delivery of PTX using CPT has not been addressed in the literature to the best of our knowledge.…”

Section: Resultsmentioning

confidence: 99%

“…The application of CPT in the delivery of anticancer drugs has been recently emerged. In a recent study by our group, we have optimized CPT to facilitate oral delivery of PTX and achieved excellent anticancer potential in treating multidrug-resistant colon cancer in a murine model . Similarly, several earlier studies exemplified delivery of anticancer drugs including PTX, cyclosporine A, and docetaxel using orally deliverable CPT, but these studies were mostly limited to in vitro evaluation.…”

Section: Introductionmentioning

confidence: 99%

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Aerosol Delivery of Paclitaxel-Containing Self-Assembled Nanocochleates for Treating Pulmonary Metastasis: An Approach Supporting Pulmonary Mechanics

Shanmugam

Joshi

Kaviratna

et al. 2020

ACS Biomater. Sci. Eng.

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Paclitaxel (PTX) is a potent anticancer agent, which is clinically administered by infusion for treating pulmonary metastasis of different cancers. Systemic injection of PTX is promising in treating pulmonary metastasis of various cancers but simultaneously leads to many severe complications in the body. In this study, we have demonstrated a noninvasive approach for delivering PTX to deep pulmonary tissues via an inhalable phospholipid-based nanocochleate platform and showed its potential in treating pulmonary metastasis of melanoma cancer. Nanocochleates have been previously explored for oral delivery of anticancer drugs; their application for aerosol-based administration has not been accomplished in the literature thus far. Our results showed that the PTX-carrying aerosol nanocochleates (PTX-CPTs) possessed excellent pulmonary surfactant action characterized by high surface activity and encouraging in vitro terminal airway patency when compared to the marketed Taxol formulation, which is known to contain a high amount of Cremophore EL. We observed under in vitro twin-impinger analysis that the PTX-CPT had a high tendency to get deposited in stage II (alveolar region of lungs), indicating the capability of CPT to reach the deep alveolar region. Further, while exposed to the human lung adenocarcinoma cell line (A549), the PTX-CPT showed excellent cytotoxicity mediated by enhanced cellular uptake via energy-dependent endocytosis. Aerosol-based administration of PTX-CPT in a pulmonary metastatic murine melanoma model (B16F10) resulted in significant (p < 0.05) tumor growth inhibition when compared to an intravenous dose of Taxol. Inhibition of tumor growth in aerosol-based PTX-CPT-treated animals was evident by the significant (p < 0.05) reduction in numbers of tumor nodules and percent metastasis area covered by melanoma cells in the lung when compared to other treatment groups. Overall, our finding suggests that PTX can be safely administered in the form of an aerosol using a newly developed CPT system, which serves a dual purpose as both a drug delivery carrier and a pulmonary surfactant in treating pulmonary metastasis.

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Section: Resultssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aerosol Delivery of Paclitaxel-Containing Self-Assembled Nanocochleates for Treating Pulmonary Metastasis: An Approach Supporting Pulmonary Mechanics

Shanmugam

Joshi

Kaviratna

et al. 2020

ACS Biomater. Sci. Eng.

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“…The percent EE and DL were calculated as follows: EE (%) = (amount of drug entrapped in cochleates or liposomes/total amount of the drug initially added) Â 100; DL (μg/mL) = amount of drug entrapped in cochleates or liposomes/total amount of lipid. 7,13 Analysis of LSP was carried out using high-performance liquid chromatography (HPLC) as previously reported. 14 The isocratic mobile phase consisted of 10 mM phosphate buffer and methanol (45:55 vol/vol), then LSP detection was achieved at 285 nm.…”

Section: Methodsmentioning

confidence: 99%

Cochleate Formulation Enhances the Stability of Lansoprazole in Acidic Condition

Goo

Jin

Kim

et al. 2021

Bulletin Korean Chem Soc

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Lansoprazole (LSP)-loaded cochleates were developed using dimyristoyl phosphatidylcholine (DMPC) and cholesterol in the presence or absence of dicetyl phosphate (DCP). Cochleates containing DCP exhibited unique cylindrical morphologies, resulting in improved LSP loading and enhanced stability in an acidic environment. Thus, we suggest that the use of negatively charged components, such as DCP, is needed to formulate cochleates using a neutrally charged lipid such as DMPC.

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“…The lower oral Paclitaxel bioavailability (<10%) is observed due to efflux of the drug by the multidrug transporter P-glycoprotein (Pgp) and excessive hepatic metabolism by the cytochrome P450 system [ 15 ]. In addition, Paclitaxel is highly lipophilic, insoluble in water, and lacks ionizable functional groups; therefore, changing pH does not enhance its solubility, and it cannot be used in a pharmaceutically different form [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies

et al. 2022

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Colorectal cancer (CRC) is considered one of the most commonly diagnosed malignant diseases. Recently, there has been an increased focus on using nanotechnology to resolve most of the limitations in conventional chemotherapy. Niosomes have great advantages that overcome the drawbacks associated with other lipid drug delivery systems. They are simple, cheap, and highly stable nanocarriers. This study investigated the effectiveness of using niosomes with their amphiphilic characteristics in the incorporation of both hydrophilic and hydrophobic anticancer drugs for CRC treatment. Methods: Drug-free niosomes were formulated using a response surface D-optimal factorial design to study the cholesterol molar ratio, surfactant molar ratio and surfactant type effect on the particle size and Z-potential of the prepared niosomes. After numerical and statistical optimization, an optimized formulation having a particle size of 194.4 ± 15.5 nm and a Z-potential of 31.8 ± 1.9 mV was selected to be loaded with Oxaliplatin and Paclitaxel separately in different concentrations. The formulations with the highest entrapment efficiency (EE%) were evaluated for their drug release using the dialysis bag method, in vitro antitumor activity on HT-29 colon cancer cell line and apoptosis activity. Results: Niosomes prepared using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at a molar ratio 4, cholesterol (2 molar ratio) and loaded with 1 molar ratio of either Oxaliplatin or Paclitaxel provided nanosized vesicles (278.5 ± 19.7 and 251.6 ± 18.1 nm) with a Z-potential value (32.7 ± 1.01 and 31.69 ± 0.98 mV) with the highest EE% (90.57 ± 2.05 and 93.51 ± 2.97) for Oxaliplatin and Paclitaxel, respectively. These formulations demonstrated up to 48 h drug release and increased the in vitro cytotoxicity and apoptosis efficiency of both drugs up to twice as much as free drugs. Conclusion: These findings suggest that different formulation composition parameters can be adjusted to obtain nanosized niosomal vesicles with an accepted Z-potential. These niosomes could be loaded with either hydrophilic drugs such as Oxaliplatin or hydrophobic drugs such as Paclitaxel. Drug-loaded niosomes, as a unique nanomicellar system, could enhance the cellular uptake of both drugs, resulting in enhanced cytotoxic and apoptosis effects against HT-29 colon cancer cells. Oxaliplatin–niosomes and Paclitaxel–niosomes can be considered promising alternative drug delivery systems with enhanced bioavailability of these two anticancer drugs for colorectal cancer treatment.

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Enhanced absorption, and efficacy of oral self-assembled paclitaxel nanocochleates in multi-drug resistant colon cancer

Cited by 18 publications

References 51 publications

Aerosol Delivery of Paclitaxel-Containing Self-Assembled Nanocochleates for Treating Pulmonary Metastasis: An Approach Supporting Pulmonary Mechanics

Aerosol Delivery of Paclitaxel-Containing Self-Assembled Nanocochleates for Treating Pulmonary Metastasis: An Approach Supporting Pulmonary Mechanics

Cochleate Formulation Enhances the Stability of Lansoprazole in Acidic Condition

Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies

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