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      저자 : Dhafir Masheta (검색결과 1 건)
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        Designing a drug delivery system for improved tumor treatment and targeting by functionalization of a cell-penetrating peptide

        Shafq Al‑azzawi,Dhafir Masheta 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.6

        Antitumor drugs activity is often limited due to the lack of satisfactory tumor specificity and bioavailability. Therefore, it is essential to conjugate the antitumor drug to a specific delivery system that can discriminate between tumors and normal tissue, and potentiate the activity. Purpose: the study was aimed to design a delivery system employing a cell-penetrating peptide, TAT, functionalized with a tumor targeting peptide, CREKA, and loaded with antitumor drug via a biodegradable linkage. Methods: the delivery system was synthesized using solid phase peptide synthesis and characterized by mass spectra and HPLC technique. Confocal microscopy and flow cytometry were used to examine the cellular uptake of the drug conjugate by malignant and normal cells whereas cell viability was tested to assess its cytotoxicity. Inhibition assay on dihydrofolate reductase (DHFR) to study the drug conjugate efficacy, and its stability examination were also performed. Results: characterization results confirmed successful synthesis of the delivery system and its conjugation with the drug. In addition, cellular translocation studies revealed higher cellular uptake of drug conjugate by malignant cell. The results also showed a better efficacy of the drug in conjugation in cytotoxicity and in the inhibition of DHFR and more stability at neutral pH medium. Conclusion: the functionalization with CREKA targeted the delivery of the antitumor drug to the malignant breast cells, decreasing its distribution to the normal cells. Hence this study demonstrated the potential of the designed delivery system to be used in delivering and translocating of therapeutic agents into a specific tumor tissue.

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