Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization
The development of a lipid nano-delivery system was attempted for three specific poly (ADP-ribose) polymerase 1 (PARP1) inhibitors: Veliparib, Rucaparib, and Niraparib. Simple lipid and dual lipid formulations with 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1′-glycerol) sodium salt (DPPG) and 1,2-dip...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/13/10/1613 |
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| author | Carlota J. F. Conceição Elin Moe Paulo A. Ribeiro Maria Raposo |
| author_facet | Carlota J. F. Conceição Elin Moe Paulo A. Ribeiro Maria Raposo |
| author_sort | Carlota J. F. Conceição |
| collection | DOAJ |
| description | The development of a lipid nano-delivery system was attempted for three specific poly (ADP-ribose) polymerase 1 (PARP1) inhibitors: Veliparib, Rucaparib, and Niraparib. Simple lipid and dual lipid formulations with 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1′-glycerol) sodium salt (DPPG) and 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) were developed and tested following the thin-film method. DPPG-encapsulating inhibitors presented the best fit in terms of encapsulation efficiency (>40%, translates into concentrations as high as 100 µM), zeta potential values (below −30 mV), and population distribution (single population profile). The particle size of the main population of interest was ~130 nm in diameter. Kinetic release studies showed that DPPG-encapsulating PARP1 inhibitors present slower drug release rates than liposome control samples, and complex drug release mechanisms were identified. DPPG + Veliparib/Niraparib presented a combination of diffusion-controlled and non-Fickian diffusion, while anomalous and super case II transport was verified for DPPG + Rucaparib. Spectroscopic analysis revealed that PARP1 inhibitors interact with the DPPG lipid membrane, promoting membrane water displacement from hydration centers. A preferential membrane interaction with lipid carbonyl groups was observed through hydrogen bonding, where the inhibitors’ protonated amine groups may be the major players in the PARP1 inhibitor encapsulation mode. |
| first_indexed | 2024-03-11T03:26:23Z |
| format | Article |
| id | doaj.art-577091e77955412da4f39bd989edf72a |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-11T03:26:23Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-577091e77955412da4f39bd989edf72a2023-11-18T02:42:14ZengMDPI AGNanomaterials2079-49912023-05-011310161310.3390/nano13101613Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and OptimizationCarlota J. F. Conceição0Elin Moe1Paulo A. Ribeiro2Maria Raposo3CEFITEC, Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalInstitute of Chemical and Biological Technology (ITQB NOVA), The New University of Lisbon, 2780-157 Oeiras, PortugalLaboratory of Instrumentation, Biomedical Engineering and Radiation Physics (LIBPhys-UNL), Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalLaboratory of Instrumentation, Biomedical Engineering and Radiation Physics (LIBPhys-UNL), Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalThe development of a lipid nano-delivery system was attempted for three specific poly (ADP-ribose) polymerase 1 (PARP1) inhibitors: Veliparib, Rucaparib, and Niraparib. Simple lipid and dual lipid formulations with 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1′-glycerol) sodium salt (DPPG) and 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) were developed and tested following the thin-film method. DPPG-encapsulating inhibitors presented the best fit in terms of encapsulation efficiency (>40%, translates into concentrations as high as 100 µM), zeta potential values (below −30 mV), and population distribution (single population profile). The particle size of the main population of interest was ~130 nm in diameter. Kinetic release studies showed that DPPG-encapsulating PARP1 inhibitors present slower drug release rates than liposome control samples, and complex drug release mechanisms were identified. DPPG + Veliparib/Niraparib presented a combination of diffusion-controlled and non-Fickian diffusion, while anomalous and super case II transport was verified for DPPG + Rucaparib. Spectroscopic analysis revealed that PARP1 inhibitors interact with the DPPG lipid membrane, promoting membrane water displacement from hydration centers. A preferential membrane interaction with lipid carbonyl groups was observed through hydrogen bonding, where the inhibitors’ protonated amine groups may be the major players in the PARP1 inhibitor encapsulation mode.https://www.mdpi.com/2079-4991/13/10/1613PARP1 inhibitorsVeliparibRucaparibNiraparibliposomescancer therapy |
| spellingShingle | Carlota J. F. Conceição Elin Moe Paulo A. Ribeiro Maria Raposo Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization Nanomaterials PARP1 inhibitors Veliparib Rucaparib Niraparib liposomes cancer therapy |
| title | Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization |
| title_full | Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization |
| title_fullStr | Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization |
| title_full_unstemmed | Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization |
| title_short | Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization |
| title_sort | liposome formulations for the strategic delivery of parp1 inhibitors development and optimization |
| topic | PARP1 inhibitors Veliparib Rucaparib Niraparib liposomes cancer therapy |
| url | https://www.mdpi.com/2079-4991/13/10/1613 |
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