Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug Delivery
It is of great significance to study the structure property and self-assembly of amphiphilic block copolymer in order to effectively and efficiently design and prepare drug delivery systems. In this work, dissipative particle dynamics (DPD) simulation method was used to investigate the structure pro...
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| Format: | Article |
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MDPI AG
2019-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/12/620 |
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| author | Zhimin Wu Manzhen Duan Di Xiong Can Yang Zhang |
| author_facet | Zhimin Wu Manzhen Duan Di Xiong Can Yang Zhang |
| author_sort | Zhimin Wu |
| collection | DOAJ |
| description | It is of great significance to study the structure property and self-assembly of amphiphilic block copolymer in order to effectively and efficiently design and prepare drug delivery systems. In this work, dissipative particle dynamics (DPD) simulation method was used to investigate the structure property and self-assembly ability of pH-responsive amphiphilic block copolymer poly(methyl methacrylate<i>-co-</i>methacrylic acid)<i>-b-</i>poly(aminoethyl methacrylate) (poly(MMA<i>-co-</i>MAA)<i>-b-</i>PAEMA). The effects of different block ratios (hydrophilic PAEMA segment and pH-sensitive PMAA segment) in copolymer on self-assembly and drug loading capacity including drug distribution were extensively investigated. The increase of hydrophilic PAEMA facilitated the formation of a typical core-shell structure as well as a hydrophobic PMAA segment. Furthermore, the optimal drug-carrier ratio was confirmed by an analysis of the drug distribution during the self-assembly process of block copolymer and model drug Ibuprofen (IBU). In addition, the drug distribution and nanostructure of IBU-loaded polymeric micelles (PMs) self-assembled from precise block copolymer (PMMA<i>-b-</i>PMAA<i>-b-</i>PAEMA) and block copolymer (poly(MMA<i>-co-</i>MAA)<i>-b-</i>PAEMA) with random pH-responsive/hydrophobic structure were evaluated, showing that almost all drug molecules were encapsulated into a core for a random copolymer compared to the analogue. The nanostructures of IBU-loaded PMs at different pH values were evaluated. The results displayed that the nanostructure was stable at pH < pK<sub>a</sub> and anomalous at pH > pK<sub>a</sub> which indicated drug release, suggesting that the PMs could be used in oral drug delivery. These findings proved that the amphiphilic block copolymer P(MMA<sub>30</sub><i>-co-</i>MAA<sub>33</sub>)<i>-b-</i>PAEMA<sub>38</sub> with random structure and pH-sensitivity might be a potential drug carrier. Moreover, DPD simulation shows potential to study the structure property of PMs self-assembled from amphiphilic block copolymer. |
| first_indexed | 2024-04-11T13:04:28Z |
| format | Article |
| id | doaj.art-012a02668b1a4884bf5dfe90ddbc50c3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T13:04:28Z |
| publishDate | 2019-11-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-012a02668b1a4884bf5dfe90ddbc50c32022-12-22T04:22:50ZengMDPI AGPharmaceutics1999-49232019-11-01111262010.3390/pharmaceutics11120620pharmaceutics11120620Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug DeliveryZhimin Wu0Manzhen Duan1Di Xiong2Can Yang Zhang3School of Chemical Engineering, Xiangtan University, Xiangtan 411105, ChinaSchool of Chemical Engineering, Xiangtan University, Xiangtan 411105, ChinaSchool of Chemical Engineering, Xiangtan University, Xiangtan 411105, ChinaDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99210, USAIt is of great significance to study the structure property and self-assembly of amphiphilic block copolymer in order to effectively and efficiently design and prepare drug delivery systems. In this work, dissipative particle dynamics (DPD) simulation method was used to investigate the structure property and self-assembly ability of pH-responsive amphiphilic block copolymer poly(methyl methacrylate<i>-co-</i>methacrylic acid)<i>-b-</i>poly(aminoethyl methacrylate) (poly(MMA<i>-co-</i>MAA)<i>-b-</i>PAEMA). The effects of different block ratios (hydrophilic PAEMA segment and pH-sensitive PMAA segment) in copolymer on self-assembly and drug loading capacity including drug distribution were extensively investigated. The increase of hydrophilic PAEMA facilitated the formation of a typical core-shell structure as well as a hydrophobic PMAA segment. Furthermore, the optimal drug-carrier ratio was confirmed by an analysis of the drug distribution during the self-assembly process of block copolymer and model drug Ibuprofen (IBU). In addition, the drug distribution and nanostructure of IBU-loaded polymeric micelles (PMs) self-assembled from precise block copolymer (PMMA<i>-b-</i>PMAA<i>-b-</i>PAEMA) and block copolymer (poly(MMA<i>-co-</i>MAA)<i>-b-</i>PAEMA) with random pH-responsive/hydrophobic structure were evaluated, showing that almost all drug molecules were encapsulated into a core for a random copolymer compared to the analogue. The nanostructures of IBU-loaded PMs at different pH values were evaluated. The results displayed that the nanostructure was stable at pH < pK<sub>a</sub> and anomalous at pH > pK<sub>a</sub> which indicated drug release, suggesting that the PMs could be used in oral drug delivery. These findings proved that the amphiphilic block copolymer P(MMA<sub>30</sub><i>-co-</i>MAA<sub>33</sub>)<i>-b-</i>PAEMA<sub>38</sub> with random structure and pH-sensitivity might be a potential drug carrier. Moreover, DPD simulation shows potential to study the structure property of PMs self-assembled from amphiphilic block copolymer.https://www.mdpi.com/1999-4923/11/12/620polymeric micellesamphiphilicdpd simulationself-assemblystructure-property |
| spellingShingle | Zhimin Wu Manzhen Duan Di Xiong Can Yang Zhang Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug Delivery Pharmaceutics polymeric micelles amphiphilic dpd simulation self-assembly structure-property |
| title | Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug Delivery |
| title_full | Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug Delivery |
| title_fullStr | Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug Delivery |
| title_full_unstemmed | Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug Delivery |
| title_short | Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug Delivery |
| title_sort | mesoscale simulations of ph responsive amphiphilic polymeric micelles for oral drug delivery |
| topic | polymeric micelles amphiphilic dpd simulation self-assembly structure-property |
| url | https://www.mdpi.com/1999-4923/11/12/620 |
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