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

Alshehri, Sultan; Alanazi, Abdullah; Elzayat, Ehab M.; Altamimi, Mohammad A.; Imam, Syed Sarim; Hussain, Afzal; Alqahtani, Faleh; Shakeel, Faiyaz

doi:10.3390/pr9071210

Cited by 23 publications

(23 citation statements)

References 22 publications

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“…For the characterization and evaluation of the samples, a Pyris manager software (Pyris Elmer, Waltham, MA, USA) was used for the solid-state characterization. 23 …”

Section: Methodsmentioning

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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“…For the characterization and evaluation of the samples, a Pyris manager software (Pyris Elmer, Waltham, MA, USA) was used for the solid-state characterization. 23 …”

Section: Methodsmentioning

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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“…In addition, the AUC 0-∞ values were 2879.75 and 4042.63 µg•L −1 •h −1 , respectively. The bioavailability of RES/RS/PEG6000 SRSD relative to the raw RES was 140.38%, combined with the increase in saturation solubility, which indicated that the SD technology can improve solubility and bioavailability [40,42,43].…”

Section: In Vivo Studymentioning

confidence: 99%

Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

Zhu

Zhang

et al. 2021

Molecules

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This study aimed to prepare a sustained-release solid dispersion of poorly water-soluble resveratrol (RES) with high melting point in a single hot melt extrusion step. A hydrophobic–hydrophilic polymeric blend (Eudragit RS and PEG6000) was used to control the release of RES. With the dispersive mixing and high shear forces of hot melt extrusion, the thermodynamic properties and dispersion of RES were changed to improve its solubility. The effects of the formulation were investigated through univariate analysis to optimize the preparation of the sustained-release solid dispersion. In vitro and in vivo studies were performed to evaluate the prepared RES/RS/PEG6000 sustained-release solid dispersion. The physical state of the solid dispersion was characterized using differential scanning calorimetry and X-ray diffraction. Surface properties of the dispersion were visualized using scanning electron microscopy, and the chemical interaction between RES and excipients was detected through Fourier-transform infrared spectroscopy. Results suggested that the optimized sustained-release solid dispersion was obtained when the mass ratio of RES-polymeric blend was 1:5, the ratio of PEG6000 was 35%, the barrel temperature was 170 °C, and the screw speed was 80 rpm. In vitro studies demonstrated that the solid dispersion showed a good sustained release effect. The cumulative release of RES reached 82.42% until 12 h and was fit by the Weibull model. In addition, the saturated solubility was 2.28 times higher than that of the bulk RES. In vitro studies demonstrated that the half-life increased from 3.78 to 7.09 h, and the bioavailability improved to 140.38%. The crystalline RES was transformed into the amorphous one, and RES was highly dispersed in the polymeric blend matrix.

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“…The weight of each sample was 3 mg and fixed inside the sealed aluminum pan. For the characterization and evaluation of the samples, a Pyris manager software (Pyris Elmer, Waltham, MA, USA) was used for the solid-state characterization [4].…”

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

“…The study was conducted using an X-ray diffractometer (Ultima IV, Rigaku Inc. Tokyo, Japan) with a scanning rate of 0.5/min in the scanning range of 3-180•. The characteristic peak of each sample was assessed by collecting the data by monochromatic radiation (Cu Kα´ 1, λ = 1.54 Å), operating at a voltage of 40 kV and current of 40 mA [4].…”

Section: Powder X-ray Diffractionmentioning

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

Cited by 23 publications

References 22 publications

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

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

Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

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

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