Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization
| Autor: | Carlota J. F. Conceição, Elin Moe, Paulo A. Ribeiro, Maria Raposo |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Nanomaterials, Vol 13, Iss 10, p 1613 (2023) |
| Druh dokumentu: | article |
| ISSN: | 2079-4991 77955412 |
| DOI: | 10.3390/nano13101613 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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