Thiết kế và Tối ưu hóa vắc-xin BCG dạng bột khô ổn định nhiệt độ

Springer Science and Business Media LLC - Tập 37 - Trang 1-14 - 2019
Dominique N. Price1,2, Nitesh K. Kunda1,3, Rajaun Ellis4,5, Pavan Muttil1
1Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Health Sciences Center, Albuquerque, USA
2Biomedical Sciences Graduate Program, University of New Mexico, Health Sciences Center, Albuquerque, USA
3Department of Pharmaceutical Sciences, College of pharmacy and Health Sciences, St. John’s University, Jamaica, USA
4Health Sciences Center University of New Mexico, Albuquerque, USA
5Nova Southeastern University, Fort Lauderdale, USA

Tóm tắt

Sự mất tác dụng của vắc-xin do tiếp xúc với nhiệt độ cực đoan trong quá trình lưu trữ và vận chuyển vẫn là một trở ngại lớn cho sự thành công của nhiều loại vắc-xin, bao gồm cả vắc-xin Bacille Calmette-Guérin (BCG), vắc-xin duy nhất hiện có đối phó với Mycobacterium tuberculosis. BCG là một loại vắc-xin sống, bị suy giảm, cần phải được lưu trữ trong tủ lạnh để duy trì tính khả thi. Trong nghiên cứu này, chúng tôi đã chế tạo một loại bột khô BCG ổn định nhiệt độ bằng cách sử dụng kỹ thuật phun sấy. Chúng tôi đã áp dụng thiết kế yếu tố để tối ưu hóa công thức của các tá dược ổn định bao gồm L-leucine, albumin huyết thanh bò, polyvinylpyrrolidone, mannitol, và trehalose. Các loại bột được đánh giá dựa trên kích thước hạt, năng suất, khả năng giữ nước và hấp thụ nước, nhiệt độ chuyển tiếp thủy tinh, và hiệu suất aerosol. Ba hỗn hợp tá chất bột tối ưu đã được lựa chọn từ thiết kế yếu tố nhằm đưa BCG vào dựa trên khả năng duy trì ổn định và đặc tính lưu lượng bột. Các loại bột vắc-xin cũng được đánh giá về khả năng sống sót của BCG và tính miễn dịch trong cơ thể sau một thời gian dài bảo quản. BCG sống đã được phun sấy thành công bằng các tá chất tối ưu hóa. Bột khô BCG không cho thấy sự mất khả năng sống (25°C, độ ẩm tương đối lên tới 60%; RH) và ~2-log mất khả năng sống (40°C, 75% RH) sau một năm lưu trữ. Kích thước khí động học của các loại bột nằm trong phạm vi có thể hít vào. Hơn nữa, khi chuột khỏe mạnh được tiêm nội bì với các loại bột BCG tái cấu trúc (được lưu trữ trong 2 năm), vắc-xin vẫn duy trì được tính miễn dịch. Chúng tôi đã phát triển một loại vắc-xin BCG phun sấy có khả năng sống và kháng nguyên sau thời gian lưu trữ dài. Theo hiểu biết của chúng tôi, đây là nghiên cứu đầu tiên cho thấy ổn định nhiệt độ phòng của vắc-xin BCG sống mà không có sự mất mát sống nào trong 12 tháng.

Từ khóa

#Vắc-xin BCG #dạng bột khô #ổn định nhiệt độ #kháng nguyên #bảo quản lâu dài.

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