Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer

Vaidya, Bhuvaneshwar; Parvathaneni, Vineela; Kulkarni, Nishant S.; Shukla, Snehal K.; Damon, Jenna K.; Sarode, Apoorva; Kanabar, Dipti; Garcia, Jerome; Mitragotri, Samir; Muth, Aaron; Gupta, Vivek

doi:10.1016/j.ijbiomac.2018.10.181

Cited by 110 publications

(36 citation statements)

References 39 publications

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“…The development of 3D in-vitro models is of utmost necessity today to mimic in-vivo solid tumor conditions, which could be achieved by using specific low attachment spheroid plates as reported by Vaidya et al [51]. Mesothelioma cell migration/invasion through a collagen matrix, as well as invasive growth into 3D collagen, was found to be decreased by pirfenidone treatment in a recent study [68].…”

Section: Discussionmentioning

confidence: 92%

“…Three cancer cell lines (A549, H460, and H4006) were evaluated for their ability to form compact spheroids using Nunclon Sphera plates, as previously reported [51]. While A549 and H460 cell lines were able to form spheroid masses from day 1 or day 3 during culture, the H4006 cell line was found to form irregular aggregates or cell clusters.…”

Section: D Spheroid Cell Culture Studymentioning

confidence: 96%

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Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

et al. 2020

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Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure in safety/efficacy studies. Drug repurposing (i.e., investigating FDA-approved drug molecules for use against new indications) provides an opportunity to shorten the drug development cycle. In this project, we propose to repurpose pirfenidone (PFD), an anti-fibrotic drug, for NSCLC treatment by encapsulation in a cationic liposomal carrier. Liposomal formulations were optimized and evaluated for their physicochemical properties, in-vitro aerosol deposition behavior, cellular internalization capability, and therapeutic potential against NSCLC cell lines in-vitro and ex-vivo. Anti-cancer activity of PFD-loaded liposomes and molecular mechanistic efficacy was determined through colony formation (1.5- to 2-fold reduction in colony growth compared to PFD treatment in H4006, A549 cell lines, respectively), cell migration, apoptosis and angiogenesis assays. Ex-vivo studies using 3D tumor spheroid models revealed superior efficacy of PFD-loaded liposomes against NSCLC, as compared to plain PFD. Hence, the potential of inhalable liposome-loaded pirfenidone in NSCLC treatment has been established in-vitro and ex-vivo, where further studies are required to determine their efficacy through in vivo preclinical studies followed by clinical studies.

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Section: Discussionmentioning

confidence: 92%

Section: D Spheroid Cell Culture Studymentioning

confidence: 96%

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

et al. 2020

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“…The cells were then dispersed in 500 µL of binding buffer and further incubation was performed for 15 min with AnnexinV FITC (2 µL) and PI (5 µL). Quantification of apoptotic cells was performed by flow cytometry using a FACS DIVA 8.0.2 [15].…”

Section: Apoptosis Assay By Flow Cytometrymentioning

confidence: 99%

Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers

Alhakamy

Shadab

2019

Pharmaceutics

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Itraconazole (ITR) is a broad-spectrum antifungal drug, which has been shown to possess some promising anticancer, anti-proliferative, and anti-angiogenic properties in some cancers, such as cancers of the lung, breast, and skin. However, ITR has some drawbacks, such as poor water solubility, which hinder its use as a therapeutic agent. Therefore, in the present study, we developed and characterized chitosan-coated PLGA nanoparticles of itraconazole and studied their anticancer activities in H1299 lung cancer cells. The prepared ITR nanoparticles showed a small particle size, narrow poly dispersity index (PDI), positive zeta potential, and a controlled drug release profile. The cytotoxicity of ITR nanoparticles (NPs) on H1299 cancer cells after 24 h of exposure was greater than that of the ITR solution. Apoptosis of cancer cells exposed to ITR nanoparticles was also enhanced in comparison with the ITR solution. At the molecular level, ITR NPs were more effective than ITR solution in inducing pro-apoptotic Bax and p53 while reducing anti-apoptotic Bcl2 protein expression. ITR NPs were more effective than ITR solution in arresting cells both at the G0/G1 as well as G2/M phases of the cell cycle. Hence, repurposing itraconazole by encapsulation into PLGA NPs with chitosan coating is a potentially promising approach to treat lung cancers.

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“…Native or non-substituted CDs and their hydroxy-propyl derivatives have been used as pharmaceutical excipients to increase drug solubility, improve chemical stability, reduce toxicity and transport molecules to specific sites [19,20,21,22,23]. Importantly, drug/CD complexation increases the aqueous solubility of poorly soluble drugs without altering their properties [24]; as a result, CDs have been used in over 40 marketed products to date.…”

Section: Introductionmentioning

confidence: 99%

Nepafenac-Loaded Cyclodextrin/Polymer Nanoaggregates: A New Approach to Eye Drop Formulation

2019

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The topical administration route is commonly used for targeting therapeutics to the eye; however, improving the bioavailability of drugs applied directly to the eye remains a challenge. Different strategies have been studied to address this challenge. One of them is the use of aggregates that are formed easily by self-assembly of cyclodextrin (CD)/drug complexes in aqueous solution. The aim of this study was to design a new eye drop formulation based on aggregates formed between CD/drug complexes. For this purpose, the physicochemical properties of the aggregates associated with six CDs and selected water-soluble polymers were analysed. Complex formation was studied using differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and 1H nuclear magnetic resonance spectroscopy (1H-NMR). Results showed that HPβCD performed best in terms of solubilization, while γCD performed best in terms of enhancing nanoaggregate formation. Formation of inclusion complexes was confirmed by DSC, FT-IR and 1H-NMR studies. A mixture of 15% (w/v) γCD and 8% (w/v) HPβCD was selected for formulation studies. It was concluded that formulations with aggregate sizes less than 1 µm and viscosity around 10–19 centipoises can be easily prepared using a mixture of CDs. Formulations containing polymeric drug/CD nanoaggregates represent an interesting strategy for enhanced topical delivery of nepafenac.

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Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer

Cited by 110 publications

References 39 publications

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers

Nepafenac-Loaded Cyclodextrin/Polymer Nanoaggregates: A New Approach to Eye Drop Formulation

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