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Tiềm năng của các prodrug amino acid/dipeptide monoester của Floxuridine trong việc tăng cường khả năng cung cấp thuốc hoạt tính đến các vị trí sâu trong khối u: Nghiên cứu in vitro trên hai lớp tế bào đơn
Tóm tắt
Để đánh giá các lợi ích của các prodrug monoester amino acid/dipeptide trong điều trị ung thư, chúng tôi đã tiến hành đánh giá sự hấp thu và tác động độc tế bào của các prodrug floxuridine trong một lớp tế bào ung thư thứ cấp sau khi đã thẩm thấu qua một lớp tế bào ung thư nguyên phát. Lớp tế bào Capan-2 đầu tiên được nuôi cấy trên các insert màng transwell; lớp tế bào thứ hai được nuôi cấy ở đáy của một đĩa. Sự thẩm thấu của floxuridine và các prodrug của nó qua lớp tế bào đầu tiên và sự hấp thu cùng thử nghiệm tăng sinh tế bào, trên lớp thứ hai, đã được xác định lần lượt. Tất cả các prodrug floxuridine đều thể hiện sự thẩm thấu tốt hơn qua lớp tế bào Capan-2 đầu tiên so với thuốc gốc. Mối liên hệ giữa sự hấp thu và ức chế tăng trưởng trong lớp thứ hai với prodrug nguyên vẹn thẩm thấu qua lớp đầu tiên cho thấy rằng độ thẩm thấu và tính ổn định enzym là thiết yếu cho tác dụng kéo dài của prodrug trong các lớp sâu hơn của khối u. Mối liên hệ giữa sự hấp thu và ức chế tăng trưởng đều vượt trội đối với các prodrug dipeptide so với các prodrug mono amino acid. Mặc dù một mối liên hệ tổng quát ban đầu giữa prodrug nguyên vẹn và sự hấp thu hoặc tác động độc tế bào đã được thiết lập, có vẻ như một hỗn hợp của các prodrug floxuridine với các đặc điểm có lợi khác nhau có thể hiệu quả hơn trong việc điều trị các khối u.
Từ khóa
#Amino Acid #Dipeptide #Monoester #Prodrug #Floxuridine #Ung thư #Thẩm thấu #Tác động độc tế bàoTài liệu tham khảo
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