Journal Article Epublish 2 citations
PubMed: 38786638 DOI: 10.3390/jfb15050127
Process Optimization of Scaled-Up Production and Biosafety Evaluation of the Dimethyl-Dioctadecyl-Ammonium Bromide/Poly(lactic acid) Nano-Vaccine.
J Funct Biomater 15(5)
Authors: Hengye Yang, Yuan Gao, Meijuan Liu, Juan Ma, Qun Lu
Affiliations
- Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Heilongjiang Provincial Key Laboratory of Ecological Utilization of Forestry-Based Active Substances, College of Chemistry, Chemistry Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China.
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
- Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Abstract
Nano-adjuvant vaccines could induce immune responses and enhance immunogenicity. However, the application and manufacturing of nano-adjuvant is hampered by its challenging scale-up, poor reproducibility, and low security. Therefore, the present study aimed to optimize the preparation nanoparticles (NPs) using FDA-approved biopolymer materials poly(lactic acid) (PLA) and cationic lipid didodecyl-dimethyl-ammonium bromide (DDAB), develop the scale-up process, and evaluate the stability and biosafety of it. The optimum preparation conditions of DDAB/PLA NPs on a small scale were as follows: DDAB amount of 30 mg, aqueous phase volume of 90 mL, stirring rate at 550 rpm, and solidifying time of 12 h. Under the optimum conditions, the size of the NPs was about 170 nm. In scale-up preparation experiments, the vacuum rotary evaporation of 6 h and the Tangential flow ultrafiltration (TFU) method were the optimum conditions. The results suggested that DDAB/PLA NPs exhibited a uniform particle size distribution, with an average size of 150.3 ± 10.4 nm and a narrow polydispersity index (PDI) of 0.090 ± 0.13, coupled with a high antigen loading capacity of 85.4 ± 4.0%. In addition, the DDAB/PLA NPs can be stored stably for 30 days and do not have side effects caused by residual solvents. For biosafety, the acute toxicity experiments showed good tolerance of the vaccine formulation even at a high adjuvant dose. The local irritation experiment demonstrated the reversibility of muscular irritation, and the repeated toxicity experiment revealed no significant necrosis or severe lesions in mice injected with the high-dose vaccine formulation. Overall, the DDAB/PLA NPs exhibit potential for clinical translation as a safe candidate vaccine adjuvant.
MeSH
Vaccines, Containment Of Biohazards, Lactic Acid, Nanovaccines