Predicting zeta potential of liposomes from their structure: A nano-QSPR model for DOPE, DC-Chol, DOTAP, and EPC formulations
Liposomes, nanoscale spherical structures composed of amphiphilic lipids, hold great promise for various pharmaceutical applications, especially as nanocarriers in targeted drug delivery, due to their biocompatibility, biodegradability, and low immunogenicity. Understanding the factors influencing t...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037024000126 |
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| author | Kamila Jarzynska Agnieszka Gajewicz-Skretna Krzesimir Ciura Tomasz Puzyn |
| author_facet | Kamila Jarzynska Agnieszka Gajewicz-Skretna Krzesimir Ciura Tomasz Puzyn |
| author_sort | Kamila Jarzynska |
| collection | DOAJ |
| description | Liposomes, nanoscale spherical structures composed of amphiphilic lipids, hold great promise for various pharmaceutical applications, especially as nanocarriers in targeted drug delivery, due to their biocompatibility, biodegradability, and low immunogenicity. Understanding the factors influencing their physicochemical properties is crucial for designing and optimizing liposomes. In this study, we have presented the kernel-weighted local polynomial regression (KwLPR) nano-quantitative structure-property relationships (nano-QSPR) model to predict the zeta potential (ZP) based on the structure of 12 liposome formulations, including 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 3ß-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and L-α-phosphatidylcholine (EPC). The developed model is well-fitted (R2 = 0.96, RMSEC = 5.76), flexible (QCVloo2 = 0.83, RMSECVloo = 10.77), and reliable (QExt2= 0.89 RMSEExt = 5.17). Furthermore, we have established the formula for computing molecular nanodescriptors for liposomes, based on constituent lipids’ molar fractions. Through the correlation matrix and principal component analysis (PCA), we have identified two key structural features affecting liposomes’ zeta potential: hydrophilic-lipophilic balance (HLB) and enthalpy of formation. Lower HLB values, indicating a more lipophilic nature, are associated with a higher zeta potential, and thus stability. Higher enthalpy of formation reflects reduced zeta potential and decreased stability of liposomes. We have demonstrated that the nano-QSPR approach allows for a better understanding of how the composition and molecular structure of liposomes affect their zeta potential, filling a gap in ZP nano-QSPR modeling methodologies for nanomaterials (NMs). The proposed proof-of-concept study is the first step in developing a comprehensive and computationally based system for predicting the physicochemical properties of liposomes as one of the most important drug nano-vehicles. |
| first_indexed | 2024-03-08T06:57:03Z |
| format | Article |
| id | doaj.art-931afa3353e84977a2327ed080cb6f0a |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T06:57:03Z |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-931afa3353e84977a2327ed080cb6f0a2024-02-03T06:35:28ZengElsevierComputational and Structural Biotechnology Journal2001-03702024-12-012538Predicting zeta potential of liposomes from their structure: A nano-QSPR model for DOPE, DC-Chol, DOTAP, and EPC formulationsKamila Jarzynska0Agnieszka Gajewicz-Skretna1Krzesimir Ciura2Tomasz Puzyn3Laboratory of Environmental Chemoinformatics, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandLaboratory of Environmental Chemoinformatics, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandLaboratory of Environmental Chemoinformatics, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland; Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gen. Hallera 107, 80-416 Gdańsk, Poland; Corresponding author at: Laboratory of Environmental Chemoinformatics, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandLaboratory of Environmental Chemoinformatics, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland; Corresponding author.Liposomes, nanoscale spherical structures composed of amphiphilic lipids, hold great promise for various pharmaceutical applications, especially as nanocarriers in targeted drug delivery, due to their biocompatibility, biodegradability, and low immunogenicity. Understanding the factors influencing their physicochemical properties is crucial for designing and optimizing liposomes. In this study, we have presented the kernel-weighted local polynomial regression (KwLPR) nano-quantitative structure-property relationships (nano-QSPR) model to predict the zeta potential (ZP) based on the structure of 12 liposome formulations, including 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 3ß-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and L-α-phosphatidylcholine (EPC). The developed model is well-fitted (R2 = 0.96, RMSEC = 5.76), flexible (QCVloo2 = 0.83, RMSECVloo = 10.77), and reliable (QExt2= 0.89 RMSEExt = 5.17). Furthermore, we have established the formula for computing molecular nanodescriptors for liposomes, based on constituent lipids’ molar fractions. Through the correlation matrix and principal component analysis (PCA), we have identified two key structural features affecting liposomes’ zeta potential: hydrophilic-lipophilic balance (HLB) and enthalpy of formation. Lower HLB values, indicating a more lipophilic nature, are associated with a higher zeta potential, and thus stability. Higher enthalpy of formation reflects reduced zeta potential and decreased stability of liposomes. We have demonstrated that the nano-QSPR approach allows for a better understanding of how the composition and molecular structure of liposomes affect their zeta potential, filling a gap in ZP nano-QSPR modeling methodologies for nanomaterials (NMs). The proposed proof-of-concept study is the first step in developing a comprehensive and computationally based system for predicting the physicochemical properties of liposomes as one of the most important drug nano-vehicles.http://www.sciencedirect.com/science/article/pii/S2001037024000126LiposomesZeta potentialNano-QSPRKwLPRPCA biplotNanodescriptors |
| spellingShingle | Kamila Jarzynska Agnieszka Gajewicz-Skretna Krzesimir Ciura Tomasz Puzyn Predicting zeta potential of liposomes from their structure: A nano-QSPR model for DOPE, DC-Chol, DOTAP, and EPC formulations Computational and Structural Biotechnology Journal Liposomes Zeta potential Nano-QSPR KwLPR PCA biplot Nanodescriptors |
| title | Predicting zeta potential of liposomes from their structure: A nano-QSPR model for DOPE, DC-Chol, DOTAP, and EPC formulations |
| title_full | Predicting zeta potential of liposomes from their structure: A nano-QSPR model for DOPE, DC-Chol, DOTAP, and EPC formulations |
| title_fullStr | Predicting zeta potential of liposomes from their structure: A nano-QSPR model for DOPE, DC-Chol, DOTAP, and EPC formulations |
| title_full_unstemmed | Predicting zeta potential of liposomes from their structure: A nano-QSPR model for DOPE, DC-Chol, DOTAP, and EPC formulations |
| title_short | Predicting zeta potential of liposomes from their structure: A nano-QSPR model for DOPE, DC-Chol, DOTAP, and EPC formulations |
| title_sort | predicting zeta potential of liposomes from their structure a nano qspr model for dope dc chol dotap and epc formulations |
| topic | Liposomes Zeta potential Nano-QSPR KwLPR PCA biplot Nanodescriptors |
| url | http://www.sciencedirect.com/science/article/pii/S2001037024000126 |
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