ELECTROPHORESIS
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2021
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IF 3.535
Hui Jiang,Hao Zhang,Shi-Jun Yin,Min Lu,Xu Wang,Feng-Qing Yang
Profiling of lipid–water partition coefficients ( K L/W ) of drugs is an essential issue during the early stage of drug development. In this study, two liposomes, including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) + cholesterol (Chol) (DSPC/Chol liposomes) and soybean lecithin (SPC) + Chol (SPC/Chol liposomes), were prepared for the liposome electrokinetic chromatography (LEKC) analysis, and the logarithm of lipid–water partition coefficients (log K L/W ) of neutral and ionic drugs were determined based on an iterative method. The log K L/W values determined by the SPC/Chol or DSPC/Chol liposomes LEKC were linearly fitted, which showed a good fitting coefficient ( R 2 = 0.89). Furthermore, the linear relationship between the data obtained from LEKC system and octanol–water system, immobilized artificial membrane, Caco-2 cell model, and software prediction was analyzed, respectively. Results illustrated that DSPC/Chol liposomes or SPC/Chol liposomes had a good linear relationship with Caco-2 cell model, and R 2 was 0.81 and 0.72, respectively. Moreover, the linear free energy relationship analysis suggested that the solute volume, hydrogen bond basicity, and J – were the main descriptors that drove the partition process of solutes in the SPC/Chol or DSPC/Chol LEKC system. In addition, the normalized properties of the SPC/Chol and DSPC/Chol LEKC systems through linear free energy relationship analysis were very close. In short, DSPC/Chol liposomes are more suitable for simulating cell membranes than SPC/Chol liposomes, and the developed LEKC is an effective partitioning model for measuring the log K L/W of drugs.
研究领域:
药学
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分析化学
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药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2021
·
IF 3.935
Hui Jiang,Shi-Jun Yin,Xu Wang,Min Lu,Hao Zhang,Feng-Qing Yang
Two liposomes , including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) + 1,2-dimyristoyl- sn -glycero-3-phosphoethanolamine (PE) + cholesterol (Chol) (DSPC/PE/Chol liposomes) and soybean lecithin (SPC) + PE + Chol (SPC/PE/Chol liposomes), were prepared and fixed on the inner wall of capillary column by using the adhesion of polydopamine (PDA) membrane and the cross-linking property of glutaraldehyde (GA). The immobilized liposome capillary column (ILCC) has good repeatability and stability based on the electrophoretic mobility of analyte . A CE method based on the immobilized liposome capillary column chromatography (ILCCC) was successfully developed to study the retention behavior of drugs on ILCC, and the logarithm of retention factor (log k ) of neutral and ionic drugs were determined. The results show that the log k measured by the ILCCC based on two liposomes have a good linear fitting (R 2 = 0.86). Moreover, the linear relationship between ILCCC system and other related research systems (octanol-water system and immobilized artificial membrane (IAM)) was analyzed, and the results indicate that SPC/PE/Chol ILCCC, DSPC/PE/Chol ILCCC and IAM systems have good fitting results, R 2 values are 0.86 and 0.78, respectively. In addition, the normalization coefficients of ILCCC and IAM systems obtained by the linear free energy relationship (LFER) analysis are close and the d value is small. In short, the ILCCC is a simple and feasible method for studying drug membrane permeability.
研究领域:
分析化学
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药学
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Kangzeng Wu,Fengwei Xu,Yongchao Dai,Shanshan Jin,Anjie Zheng,Ning Zhang,Yuhong Xu
Lipid nanoparticles (LNPs) used for nonviral gene delivery have achieved significant success, particularly in COVID-19 mRNA vaccines. LNPs are routinely characterized by their particle size, polydispersity, and mRNA loading efficiency. However, the internal structure of these particles has not been specified, despite evidence showing that LNPs can be highly heterogeneous, with variations in lipid composition and preparation methods. How these structural features contributed to mRNA LNP vaccine activities is also unclear. In this study, we prepared LNPs with distinctly different internal structures. They were named the emulsion-like LNPs (eLNPs) and membrane-rich LNPs (mLNPs) respectively and compared with the classic “bleb” structure LNPs (cLNPs). The eLNPs contained higher molar percent of the ionizable lipid and lower molar percent of DSPC and cholesterol. The different lipid organization structures lead to varying mRNA delivery activities in vitro and in vivo. After intramuscular injection, eLNPs remained at the injection site and expressed antigens locally. The resulted immune responses had a very fast onset (higher titer at week 2) and lasted longer and stronger (higher titers at week 8) than other LNPs (cLNPs and mLNPs). We hypothesize that the rapid onset and local expression of antigens by muscle cells in the eLNP groups may be favored by the antigen recognition and presentation process, despite the overall mRNA expression activities was not as high especially in liver and other organ. Our data support that eLNPs are potentially the more suitable delivery system for mRNA vaccine due to their high immunogenicity and low systemic toxicity.
研究领域:
药学
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免疫学
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纳米技术
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疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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