• •
收稿日期:
2024-06-12
修回日期:
2024-07-19
出版日期:
2024-07-23
通讯作者:
周健
作者简介:
何杰锋(1999—),男,硕士研究生,1964870228@qq.com
基金资助:
Jiefeng HE(), Zhaohong MIAO, Jian ZHOU(
)
Received:
2024-06-12
Revised:
2024-07-19
Online:
2024-07-23
Contact:
Jian ZHOU
摘要:
采用耗散粒子动力学模拟方法研究了由两性离子化合物(PCBMA)或聚乙二醇化合物(PEGMA)修饰的聚赖氨酸-聚乳酸共聚物负载KLA肽和阿霉素的自组装结构与药物负载和释放行为。探讨了共聚物嵌段比、共聚物浓度、载药浓度、离子强度对载药胶束自组装的影响。结果表明,相较于PEGMA体系,当嵌段比变化时,PCBMA体系始终具有良好的胶束结构稳定性,且能在更宽的浓度范围内形成球形胶束。此外,随着载药浓度增高,PCBMA体系载药稳定性强于药物偏心分布的PEGMA体系;随着离子强度增强,其球形胶束结构形成加快。酸性pH条件下,PCBMA体系的药物释放过程符合“膨胀-解胶束化-释放”的机制,PEGMA体系的释放行为过快且不均匀。本研究在介观尺度上为探究聚合物胶束对抗菌肽与抗癌药物的双重载药/药物释放提供了参考,对优化开发载药材料具有一定指导意义。
中图分类号:
何杰锋, 苗朝虹, 周健. 两性离子共聚物负载和释放抗菌肽的计算机模拟研究[J]. 化工学报, DOI: 10.11949/0438-1157.20240650.
Jiefeng HE, Zhaohong MIAO, Jian ZHOU. Computer simulations on the loading and release of antimicrobial peptides by zwitterionic copolymers[J]. CIESC Journal, DOI: 10.11949/0438-1157.20240650.
aij | K | O | M | E | B | P | L | A | D1 | D2 | D3 | W | Na+ | Cl- |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
K | 104.9 | |||||||||||||
O | 113.2 | 104.9 | ||||||||||||
M | 110.1 | 113.5 | 104.9 | |||||||||||
E | 112.5 | 110.5 | 106.0 | 104.9 | ||||||||||
B | 115.3 | 112.5 | 114.8 | / | 104.9 | |||||||||
P | 106.9 | 111.2 | 112.4 | 108.5 | 110.4 | 104.9 | ||||||||
L | 112.4 | 117.8 | 110.2 | 107.0 | 121.2 | 107.5 | 104.9 | |||||||
A | 108.6 | 113.4 | 113.5 | 107.4 | 109.3 | 106.7 | 105.3 | 104.9 | ||||||
D1 | 129.1 | 122.5 | 118.3 | 118.8 | 136.5 | 119.3 | 113.4 | 119.2 | 104.9 | |||||
D2 | 122.4 | 119.3 | 112.5 | 111.7 | 126.9 | 109.8 | 111.4 | 114.1 | 105.0 | 104.9 | ||||
D3 | 114.5 | 116.3 | 116.3 | 109.5 | 119.6 | 107.5 | 107.2 | 110.4 | 108.3 | 109.5 | 104.9 | |||
W | 124.1 | 128.1 | 127.6 | 114.6 | 105.6 | 124.6 | 138.4 | 117.1 | 166.3 | 148.5 | 141.2 | 104.9 | ||
Na+ | 124.1 | 128.1 | 127.6 | 114.6 | 105.6 | 124.6 | 138.4 | 117.1 | 166.3 | 148.5 | 141.2 | 104.9 | 104.9 | |
Cl- | 124.1 | 128.1 | 127.6 | 114.6 | 105.6 | 124.6 | 138.4 | 117.1 | 166.3 | 148.5 | 141.2 | 104.9 | 104.9 | 104.9 |
表1 不同珠子之间的排斥参数aij
Table 1 Repulsive parameters aij between different beads
aij | K | O | M | E | B | P | L | A | D1 | D2 | D3 | W | Na+ | Cl- |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
K | 104.9 | |||||||||||||
O | 113.2 | 104.9 | ||||||||||||
M | 110.1 | 113.5 | 104.9 | |||||||||||
E | 112.5 | 110.5 | 106.0 | 104.9 | ||||||||||
B | 115.3 | 112.5 | 114.8 | / | 104.9 | |||||||||
P | 106.9 | 111.2 | 112.4 | 108.5 | 110.4 | 104.9 | ||||||||
L | 112.4 | 117.8 | 110.2 | 107.0 | 121.2 | 107.5 | 104.9 | |||||||
A | 108.6 | 113.4 | 113.5 | 107.4 | 109.3 | 106.7 | 105.3 | 104.9 | ||||||
D1 | 129.1 | 122.5 | 118.3 | 118.8 | 136.5 | 119.3 | 113.4 | 119.2 | 104.9 | |||||
D2 | 122.4 | 119.3 | 112.5 | 111.7 | 126.9 | 109.8 | 111.4 | 114.1 | 105.0 | 104.9 | ||||
D3 | 114.5 | 116.3 | 116.3 | 109.5 | 119.6 | 107.5 | 107.2 | 110.4 | 108.3 | 109.5 | 104.9 | |||
W | 124.1 | 128.1 | 127.6 | 114.6 | 105.6 | 124.6 | 138.4 | 117.1 | 166.3 | 148.5 | 141.2 | 104.9 | ||
Na+ | 124.1 | 128.1 | 127.6 | 114.6 | 105.6 | 124.6 | 138.4 | 117.1 | 166.3 | 148.5 | 141.2 | 104.9 | 104.9 | |
Cl- | 124.1 | 128.1 | 127.6 | 114.6 | 105.6 | 124.6 | 138.4 | 117.1 | 166.3 | 148.5 | 141.2 | 104.9 | 104.9 | 104.9 |
图8 酸性pH条件下载药胶束的药物释放过程: (a)PCBMA体系,(b)PEGMA体系
Fig.8 Drug release processes of drug-loading micelles (a) PCBMA system and (b) PEGMA system under the acidic pH condition
图9 不同pH条件下的RDF曲线: (a)中性PCBMA体系,(b)酸性PCBMA体系,(c)中性PEGMA体系,(d)酸性PEGMA体系
Fig.9 RDF profiles at different pH conditions (a) PCBMA system at the neutral condition; (b) PCBMA system at the acidic condition; (c) PEGMA system with at the neutral condition; (d) PEGMA system at the acidic condition
1 | Moretta A, Scieuzo C, Petrone A M, et al. Antimicrobial peptides: a new hope in biomedical and pharmaceutical fields[J]. Frontiers in Cellular and Infection Microbiology, 2021, 11: 668632. |
2 | Jenssen H, Hamill P, Hancock R E W. Peptide antimicrobial agents[J]. Clinical Microbiology Reviews, 2006, 19(3): 491-511. |
3 | Zhang Q Y, Yan Z B, Meng Y M, et al. Antimicrobial peptides: mechanism of action, activity and clinical potential[J]. Military Medical Research, 2021, 8(1): 48. |
4 | Tan P, Fu H Y, Ma X. Design, optimization, and nanotechnology of antimicrobial peptides: From exploration to applications[J]. Nano Today, 2021, 39: 101229. |
5 | Wang C, Hong T T, Cui P F, et al. Antimicrobial peptides towards clinical application: Delivery and formulation[J]. Advanced Drug Delivery Reviews, 2021, 175: 113818. |
6 | Friede M, Muller S, Briand J P, et al. Induction of immune response against a short synthetic peptide antigen coupled to small neutral liposomes containing monophosphoryl lipid A[J]. Molecular Immunology, 1993, 30(6): 539-547. |
7 | van Gent M E, Ali M, Nibbering P H, et al. Current advances in lipid and polymeric antimicrobial peptide delivery systems and coatings for the prevention and treatment of bacterial infections[J]. Pharmaceutics, 2021, 13(11): 1840. |
8 | Ghasemiyeh P, Mohammadi-Samani S. Hydrogels as drug delivery systems; pros and cons[J]. Trends in Pharmaceutical Sciences, 2019, 5(1): 7-24. |
9 | Figueiras A, Domingues C, Jarak I, et al. New advances in biomedical application of polymeric micelles[J]. Pharmaceutics, 2022, 14(8): 1700. |
10 | Kumar P, Pletzer D, Haney E F, et al. Aurein-derived antimicrobial peptides formulated with pegylated phospholipid micelles to target methicillin-resistant staphylococcus aureus skin infections[J]. ACS Infectious Diseases, 2019, 5(3): 443-453. |
11 | Knop K, Hoogenboom R, Fischer D, et al. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives[J]. Angewandte Chemie (International Ed. in English), 2010, 49(36): 6288-6308. |
12 | Li M Z, Zhang W, Li J X, et al. Zwitterionic polymers: Addressing the barriers for drug delivery[J]. Chinese Chemical Letters, 2023, 34(11): 108177. |
13 | He Y, Hower J, Chen S F, et al. Molecular simulation studies of protein interactions with zwitterionic phosphorylcholine self-assembled monolayers in the presence of water[J]. Langmuir, 2008, 24(18): 10358-10364. |
14 | Harijan M, Singh M. Zwitterionic polymers in drug delivery: a review[J]. Journal of Molecular Recognition: JMR, 2022, 35(1): e2944. |
15 | Dong P, Zhou Y, He W W, et al. A strategy for enhanced antibacterial activity against Staphylococcus aureus by the assembly of alamethicin with a thermo-sensitive polymeric carrier[J]. Chemical Communications, 2016, 52(5): 896-899. |
16 | Ivanova A, Ivanova K, Tzanov T. Simultaneous ultrasound-assisted hybrid polyzwitterion/antimicrobial peptide nanoparticles synthesis and deposition on silicone urinary catheters for prevention of biofilm-associated infections[J]. Nanomaterials, 2021, 11(11): 3143. |
17 | Răileanu M, Lonetti B, Serpentini C L, et al. Encapsulation of a cationic antimicrobial peptide into self-assembled polyion complex nano-objects enhances its antitumor properties[J]. Journal of Molecular Structure, 2022, 1249: 131482. |
18 | Wang C H, Feng S L, Qie J K, et al. Polyion complexes of a cationic antimicrobial peptide as a potential systemically administered antibiotic[J]. International Journal of Pharmaceutics, 2019, 554: 284-291. |
19 | Sun J W, Jiang L, Lin Y, et al. Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides[J]. International Journal of Nanomedicine, 2017, 12: 1517-1537. |
20 | Lim C, Won W R, Moon J, et al. Co-delivery of d-(KLAKLAK)2 peptide and doxorubicin using a pH-sensitive nanocarrier for synergistic anticancer treatment[J]. Journal of Materials Chemistry B, 2019, 7(27): 4299-4308. |
21 | Wang W, Ye Z, Gao H L, et al. Computational pharmaceutics - A new paradigm of drug delivery[J]. Journal of Controlled Release, 2021, 338: 119-136. |
22 | 苏运祥, 全学波, 闵文凤, 等. PAMAM树状大分子负载和释放阿霉素的耗散粒子动力学模拟[J]. 化工学报, 2017, 68(5): 1757-1766. |
Su Y X, Quan X B, Min W F, et al. Dissipative particle dynamics simulations on loading and release of doxorubicin by PAMAM dendrimers[J]. CIESC Journal, 2017, 68(5): 1757-1766. | |
23 | 胡建波, 刘洪超, 胡齐, 等. 有机笼跨细胞膜易位行为的分子动力学模拟研究[J]. 化工学报, 2023, 74(9): 3756-3765. |
Hu J B, Liu H C, Hu Q, et al. Molecular dynamics simulation insight into translocation behavior of organic cage across the cellular membrane[J]. CIESC Journal, 2023, 74(9): 3756-3765. | |
24 | Feng Y H, Zhang X P, Zhao Z Q, et al. Dissipative particle dynamics aided design of drug delivery systems: a review[J]. Molecular Pharmaceutics, 2020, 17(6): 1778-1799. |
25 | Liao M R, Gong H N, Quan X B, et al. Intramembrane nanoaggregates of antimicrobial peptides play a vital role in bacterial killing[J]. Small, 2023, 19(3): e2204428. |
26 | Ulmschneider J P, Ulmschneider M B. Molecular dynamics simulations are redefining our view of peptides interacting with biological membranes[J]. Accounts of Chemical Research, 2018, 51(5): 1106-1116. |
27 | Asadzadeh H, Moosavi A. Investigation of the interactions between Melittin and the PLGA and PLA polymers: molecular dynamic simulation and binding free energy calculation[J]. Materials Research Express, 2019, 6(5): 055318. |
28 | Nejabat M, Soltani F, Alibolandi M, et al. Smac peptide and doxorubicin-encapsulated nanoparticles: design, preparation, computational molecular approach and in vitro studies on cancer cells[J]. Journal of Biomolecular Structure & Dynamics, 2022, 40(2): 807-819. |
29 | Guo W X, Hu L F, Feng Y H, et al. Advances in self-assembling of pH-sensitive polymers: a mini review on dissipative particle dynamics[J]. Colloids and Surfaces B: Biointerfaces, 2022, 210: 112202. |
30 | Chen Z, Huo J H, Hao L X, et al. Multiscale modeling and simulations of responsive polymers[J]. Current Opinion in Chemical Engineering, 2019, 23: 21-33. |
31 | Wang J H, Han Y F, Xu Z Y, et al. Dissipative particle dynamics simulation: a review on investigating mesoscale properties of polymer systems[J]. Macromolecular Materials and Engineering, 2021, 306(4): e2000724. |
32 | Su Y X, Quan X B, Li L B, et al. Computer simulation of DNA condensation by PAMAM dendrimer[J]. Macromolecular Theory and Simulations, 2018, 27(2): e1700070. |
33 | Zeng S J, Quan X B, Zhu H L, et al. Computer simulations on a pH-responsive anticancer drug delivery system using zwitterion-grafted polyamidoamine dendrimer unimolecular micelles[J]. Langmuir, 2021, 37(3): 1225-1234. |
34 | Miao Z H, Chen Z, Wang L, et al. Dual-responsive zwitterion-modified nanopores: a mesoscopic simulation study[J]. Journal of Materials Chemistry. B, 2022, 10(14): 2740-2749. |
35 | Hoogerbrugge P J, Koelman J M V A. Simulating microscopic hydrodynamic phenomena with dissipative particle dynamics[J]. EPL (Europhysics Letters), 1992, 19: 155. |
36 | Groot R D, Warren P B. Dissipative particle dynamics: Bridging the gap between atomistic and mesoscopic simulation[J]. The Journal of Chemical Physics, 1997, 107(11): 4423-4435. |
37 | Groot R D. Electrostatic interactions in dissipative particle dynamics—simulation of polyelectrolytes and anionic surfactants[J]. The Journal of Chemical Physics, 2003, 118(24): 11265-11277. |
38 | Wang Y L, Laaksonen A, Lu Z Y. Implementation of non-uniform FFT based Ewald summation in dissipative particle dynamics method[J]. Journal of Computational Physics, 2013, 235: 666-682. |
39 | Groot R D, Madden T J. Dynamic simulation of diblock copolymer microphase separation[J]. The Journal of Chemical Physics, 1998, 108(20): 8713-8724. |
40 | Wei J C, Liu Y W, Song F. Coarse-grained simulation of the translational and rotational diffusion of globular proteins by dissipative particle dynamics[J]. The Journal of Chemical Physics, 2020, 153(23): 234902. |
41 | Fan C F, Olafson B D, Blanco M, et al. Application of molecular simulation to derive phase diagrams of binary mixtures[J]. Macromolecules, 1992, 25(14): 3667-3676. |
42 | Zhu Y L, Liu H, Li Z W, et al. GALAMOST: GPU-accelerated large-scale molecular simulation toolkit[J]. Journal of Computational Chemistry, 2013, 34(25): 2197-2211. |
43 | Song X Y, Zhao S L, Fang S W, et al. Mesoscopic simulations of adsorption and association of PEO-PPO-PEO triblock copolymers on a hydrophobic surface: from mushroom hemisphere to rectangle brush[J]. Langmuir, 2016, 32(44): 11375-11385. |
44 | Yang S C, Zhu Y L, Qian H J, et al. Molecular dynamics simulation of antipolyelectrolyte effect and solubility of polyzwitterions[J]. Chemical Research in Chinese Universities, 2017, 33(2): 261-267. |
45 | Ma M K, Ahsan B, Wang J H, et al. Supramolecular crosslinks enable PIC micelles with tuneable salt stability and diverse properties[J]. Soft Matter, 2019, 15(41): 8210-8218. |
[1] | 秦晗淞, 李国梁, 闫昊, 冯翔, 刘熠斌, 陈小博, 杨朝合. 多级孔ZSM-5分子筛中油酸甲酯催化裂解吸附和扩散行为模拟研究[J]. 化工学报, 2024, 75(5): 1870-1881. |
[2] | 张文惠, 唐茹意, 崔希利, 邢华斌. 羧酸端基Y型全氟聚醚的氟谱解析及结构表征[J]. 化工学报, 2024, 75(4): 1718-1723. |
[3] | 司友明, 郑凌峰, 陈鹏忠, 樊江莉, 彭孝军. 新型锑氧簇光刻胶的性能与机理研究[J]. 化工学报, 2024, 75(4): 1705-1717. |
[4] | 赵金鹏, 张永民, 兰斌, 罗节文, 赵碧丹, 王军武. 气固鼓泡床结构双流体传热模型及其模拟验证[J]. 化工学报, 2024, 75(4): 1497-1507. |
[5] | 肖扬可, 常印龙, 李平, 王文俊, 李伯耿, 刘平伟. 动态化学交联聚烯烃类弹性体研究进展[J]. 化工学报, 2024, 75(4): 1394-1413. |
[6] | 刘静, 杨文博, 吕英迪, 陶胜洋. 喷雾-反溶剂结晶法制备掺杂铝粉的复合微球[J]. 化工学报, 2024, 75(4): 1724-1734. |
[7] | 吴立盛, 刘杰, 王添添, 罗正鸿, 周寅宁. 开环易位烯烃聚合物的动态交联改性研究进展[J]. 化工学报, 2024, 75(4): 1118-1136. |
[8] | 周康, 王建新, 于海, 魏朝良, 范丰奇, 车昕昊, 张磊. 基于分子动力学模拟的矿物基础油泡沫破裂性能研究[J]. 化工学报, 2024, 75(4): 1668-1678. |
[9] | 刘东飞, 张帆, 刘铮, 卢滇楠. 机器学习势及其在分子模拟中的应用综述[J]. 化工学报, 2024, 75(4): 1241-1255. |
[10] | 张政, 汪妩琼, 张雅静, 王康军, 吉远辉. 理论计算在药物制剂设计中的研究进展[J]. 化工学报, 2024, 75(4): 1429-1438. |
[11] | 成文凯, 颜金钰, 王嘉骏, 冯连芳. 卧式捏合反应器及其在聚合工业中的研究进展[J]. 化工学报, 2024, 75(3): 768-781. |
[12] | 吴凡, 彭旭东, 江锦波, 孟祥铠, 梁杨杨. 分子动力学模拟预测天然气密度和黏度的可行性研究[J]. 化工学报, 2024, 75(2): 450-462. |
[13] | 麻雪怡, 刘克勤, 胡激江, 姚臻. POE溶液聚合反应器内混合与反应过程的CFD研究[J]. 化工学报, 2024, 75(1): 322-337. |
[14] | 朱娇, 栾丽萍, 从深震, 刘新磊. 氢气分离有机膜[J]. 化工学报, 2024, 75(1): 138-158. |
[15] | 宋明昊, 赵霏, 刘淑晴, 李国选, 杨声, 雷志刚. 离子液体脱除模拟油中挥发酚的多尺度模拟与研究[J]. 化工学报, 2023, 74(9): 3654-3664. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||