2. Academic Validation
  3. A natural protein based platform for the delivery of Temozolomide acid to glioma cells

A natural protein based platform for the delivery of Temozolomide acid to glioma cells

  • Eur J Pharm Biopharm. 2021 Dec;169:297-308. doi: 10.1016/j.ejpb.2021.10.007.
Dina O Helal 1,  Nadia Rouatbi 2,  Shunping Han 2,  Julie Tzu-Wen Wang 2,  Adam A Walters 2,  Mona M A Abdel-Mottaleb 3,  Amany O Kamel 3,  Ahmed-Shawky Geneidi 3,  Gehanne A S Awad 3,  Khuloud T Al-Jamal 4
Affiliations

Affiliations

  • 1 School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Monazzamet El Wehda El Afrikeya Street, Abbasseya, Cairo, Egypt.
  • 2 School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
  • 3 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Monazzamet El Wehda El Afrikeya Street, Abbasseya, Cairo, Egypt.
  • 4 School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom. Electronic address: khuloud.al-jamal@kcl.ac.uk.
PMID: 34678408 DOI: 10.1016/j.ejpb.2021.10.007
Abstract

Glioblastoma is one of the most difficult to treat cancers with poor prognosis and survival of around one year from diagnosis. Effective treatments are desperately needed. This work aims to prepare temozolomide acid (TMZA) loaded albumin nanoparticles, for the first time, to target glioblastoma (GL261) and brain Cancer Stem Cells (BL6). TMZA was loaded into human serum albumin nanoparticles (HSA NPs) using the desolvation method. A response surface 3-level factorial design was used to study the effect of different formulation parameters on the drug loading and particle size of NPs. The optimum conditions were found to be: 4 mg TMZA with 0.05% sodium cholate. This yielded NPs with particle size and drug loading of 111.7 nm and 5.5% respectively. The selected formula was found to have good shelf life and serum stability but with a relatively fast drug release pattern. The optimized NPs showed excellent cellular uptake with ∼ 50 and 100% of cells were positive for NP uptake after 24 h incubation with both GL261 and BL6 glioblastoma cell lines, respectively. The selected formula showed high cytotoxicity with ̴ 20% cell viability at 1 mM TMZA after 72 h incubation time. Finally, the fluorescently labelled NPs showed co-localization with the bioluminescent syngeneic BL6 intra-cranial tumour mouse model after intravenous administration.

Keywords

Glioma; Human serum albumin; Nanoparticles; SPARC; Temozolomide acid.

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