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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Abstract

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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Author and article information

Contributors

Abdelrahman Y. Sherif: ashreef@ksu.edu.sa

Journal

Journal ID (nlm-ta): AAPS PharmSciTech

Journal ID (iso-abbrev): AAPS PharmSciTech

Title: AAPS PharmSciTech

Publisher: Springer International Publishing (Cham )

ISSN (Electronic): 1530-9932

Publication date (Electronic): 1 July 2022

Publication date Collection: August 2022

Volume: 23

Issue: 6

Electronic Location Identifier: 183

Affiliations

[1 ]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, , King Saud University, ; Riyadh, Saudi Arabia

[2 ]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Department of Pharmaceutics, College of Pharmacy, , King Saud University, ; Riyadh, Saudi Arabia

[3 ]GRID grid.411303.4, ISNI 0000 0001 2155 6022, Department of Biochemistry and Molecular Biology, College of Pharmacy, , Al-Azhar University, ; Nasr City, Cairo Egypt

[4 ]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Department of Pharmacognosy, College of Pharmacy, , King Saud University, ; Riyadh, Saudi Arabia

Article

Publisher ID: 2332

DOI: 10.1208/s12249-022-02332-7

PMC ID: 9247939

PubMed ID: 35773422

SO-VID: 4b53e4b8-d816-489c-9551-1bd72afe7620

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.