Development of novel S PC-3 gefitinib lipid nanoparticles for effective drug delivery in breast cancer. Tissue distribution studies and cell cytotoxicity analysis

Nayek, Sujit; Raghavendra, Narasimha; Kumar, Bipul

doi:10.1016/j.jddst.2020.102073

Cited by 21 publications

(32 citation statements)

References 45 publications

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“…For this purpose, high doses of chemotherapeutic agents are administered to patients which causes high systemic toxicity. Therefore, enhancing the cytotoxic effect of administered chemotherapeutic agent decreases the required therapeutic response besides low side effects [37]. Along with, encapsulation of therapeutic agents within an appropriate lipoprotein mimic carrier enhances cellular uptake and lung biodistribution [64].…”

Section: Apoptotic Studymentioning

confidence: 99%

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Engineered Nanoscale Lipid-Based Formulation as Potential Enhancer of Gefitinib Lymphatic Delivery: Cytotoxicity and Apoptotic Studies Against the A549 Cell Line

et al. 2022

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The present study aimed to engineer a nanoscale lipid-based lymphatic drug delivery system with D-α-Tocopherol polyethylene glycol 1000 succinate to combat the lymphatic metastasis of lung cancer. The nanoscale lipid-based systems including GEF-SLN, GEF-NLC, and GEF-LE were prepared and pharmaceutically characterized. In addition, the most stable formulation (GEF-NLC) was subjected to an in vitro release study. Afterward, the optimized GEF-NLC was engineered with TPGS (GEF-TPGS-NLC) and subjected to in vitro cytotoxicity, and apoptotic studies using the A549 cells line as a surrogate model for lung cancer. The present results revealed that particle size and polydispersity index of freshly prepared formulations were ranging from 198 to 280 nm and 0.106 to 0.240, respectively, with negative zeta potential ranging from − 14 to − 27.6.mV. An in vitro release study showed that sustained drug release was attained from GEF-NLC containing a high concentration of lipid. In addition, GEF-NLC and GEF-TPGS-NLC showed remarkable entrapment efficiency above 89% and exhibited sustained release profiles. Cytotoxicity showed that IC 50 of pure GEF was 11.15 μg/ml which decreased to 7.05 μg/ml for GEF-TPGS-NLC. The apoptotic study revealed that GEF-TPGS-NLC significantly decreased the number of living cells from 67 to 58% when compared with pure GEF. The present results revealed that the nanoscale and lipid composition of the fabricated SLN, NLC, and LE could mediate the lymphatic uptake of GEF to combat the lymphatic tumor metastasis. Particularly, GEF-TPGS-NLC is a promising LDDS to increase the therapeutic outcomes of GEF during the treatment of metastatic lung cancer.

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Section: Apoptotic Studymentioning

confidence: 99%

“…It is approved by FDA for the treatment of non-small lung cancer [28]. Moreover, various researches showed that GEF has cytotoxic activity against hepatocellular carcinoma [48], colorectal cancer [30], and breast cancer [36]. Furthermore, GEF exhibits antiviral activity against various types of viruses including SARS-Cov-2 [6,26].…”

Section: Introductionmentioning

confidence: 99%

Engineered Nanoscale Lipid-Based Formulation as Potential Enhancer of Gefitinib Lymphatic Delivery: Cytotoxicity and Apoptotic Studies Against the A549 Cell Line

et al. 2022

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“… 8 Furthermore, the incorporation of the drug within the lipid core protects it from chemical degradation and controls drug release if desirable. 9 In addition, drug absorption through the intestinal membrane occurs either through the nanoparticle uptake mechanism or through passive drugs transported after dissolution. 10 Besides, the nano-sized and presence of lipid materials enhances LDD through M cells.…”

Section: Introductionmentioning

confidence: 99%

“…EGFRs are commonly overexpressed on the membranes of highly proliferated tumor cells including lung cancer. 9 GEF is approved by the FDA as a first-line for the treatment of non-small cell lung cancer. 14 Furthermore, GEF is documented to inhibit the growth of different cancer cell lines, such as colorectal cancer, 15 breast cancer, 16 and hepatocellular carcinoma.…”

Section: Introductionmentioning

confidence: 99%

PEGylated SLN as a Promising Approach for Lymphatic Delivery of Gefitinib to Lung Cancer

Sherif¹,

Harisa²,

Alanazi³

et al. 2022

IJN

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Purpose The present study aimed to develop gefitinib-loaded solid lipid nanoparticles (GEF-SLN), and GEF-loaded PEGylated SLN (GEF-P-SLN) for targeting metastatic lung cancer through the lymphatic system. Methods The prepared SLNs were characterized in terms of physicochemical properties, entrapment efficiency, and in-vitro release. Furthermore, ex-vivo permeability was investigated using the rabbit intestine. Cytotoxicity and apoptotic effects were studied against A549 cell lines as a model for lung cancer. Results The present results revealed that the particle size and polydispersity index of the prepared formulations range from 114 to 310 nm and 0.066 to 0.350, respectively, with negative zeta-potential (−14 to −27.6). Additionally, SLN and P-SLN showed remarkable entrapment efficiency above 89% and exhibited sustained-release profiles. The permeability study showed that GEF-SLN and GEF-P-SLN enhanced the permeability of GEF by 1.71 and 2.64-fold, respectively, compared with GEF suspension. Cytotoxicity showed that IC 50 of pure GEF was 3.5 μg/mL, which decreased to 1.95 and 1.8 μg/mL for GEF-SLN and GEF-P-SLN, respectively. Finally, the apoptotic study revealed that GEF-P-SLN decreased the number of living cells from 49.47 to 3.43 when compared with pure GEF. Conclusion These results concluded that GEF-P-SLN is a promising approach to improving the therapeutic outcomes of GEF in the treatment of metastatic lung cancer.

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“…The SDs offer several advantages as drug delivery carriers, which includes reduction in drug particle size at molecular level, enhancement in porosity, improvement in wettability, and conversion of crystalline form of drugs into amorphous forms [7][8][9][10][11][12]. Different formulation strategies such as microparticlesbased spray-dried SDs [8], polymeric nanoparticles [9][10][11][12][13][14], solid lipid nanoparticles [15,16], nanostructured lipid carriers [17], nanosuspension [18], PEGylated immunostimulatory nanocarrier [19], nanoemulsion [20], and nanoliposomes [21] of Gef have been studied in order to enhance its dissolution/bioavailability and anticancer therapy. The Gef is a poorly water-soluble compound with poor oral bioavailability [4].…”

Section: Introductionmentioning

confidence: 99%

Formulation, In Vitro and In Vivo Evaluation of Gefitinib Solid Dispersions Prepared Using Different Techniques

et al. 2021

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Gefitinib (Gef) is a poorly water-soluble antitumor drug, which shows poor absorption/bioavailability after oral administration. Therefore, this study was carried out to develop Gef solid dispersions (SDs) using different carriers and different techniques in order to enhance its dissolution and oral absorption/bioavailability. Various SD formulations of Gef were established using fusion and microwave methods utilizing Soluplus, Kollidone VA64, and polyethylene glycol 4000 (PEG 4000) as the carriers. Developed SDs of Gef were characterized physicochemically and evaluated for in vitro dissolution and in vivo pharmacokinetic studies. The physicochemical evaluation revealed the formation of Gef SDs using fusion and microwave methods. In vitro dissolution studies indicated significant release of Gef from all SDs compared to the pure Gef. Optimized SD of Gef (S2-MW) presented significant release of Gef (82.10%) compared with pure Gef (21.23%). The optimized Gef SD (S2) was subjected to in vivo pharmacokinetic evaluation in comparison with pure Gef in rats. The results indicated significant enhancement in various pharmacokinetic parameters of Gef from an optimized SD S2 compared to the pure Gef. In addition, Gef-SD S2 resulted in remarkable improvement in bioavailability compared to the pure Gef. Overall, this study suggested that the prepared Gef-SD by microwave method showed marked enhancement in dissolution and bioavailability.

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Development of novel S PC-3 gefitinib lipid nanoparticles for effective drug delivery in breast cancer. Tissue distribution studies and cell cytotoxicity analysis

Cited by 21 publications

References 45 publications

Engineered Nanoscale Lipid-Based Formulation as Potential Enhancer of Gefitinib Lymphatic Delivery: Cytotoxicity and Apoptotic Studies Against the A549 Cell Line

Engineered Nanoscale Lipid-Based Formulation as Potential Enhancer of Gefitinib Lymphatic Delivery: Cytotoxicity and Apoptotic Studies Against the A549 Cell Line

PEGylated SLN as a Promising Approach for Lymphatic Delivery of Gefitinib to Lung Cancer

Formulation, In Vitro and In Vivo Evaluation of Gefitinib Solid Dispersions Prepared Using Different Techniques

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