Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization

Abstract

first_pagesettingsOrder Article Reprints Open AccessArticle Liposome Formulations for the Strategic Delivery of PARP1 Inhibitors: Development and Optimization by Carlota J. F. Conceição 1,2ORCID,Elin Moe 3,4,Paulo A. Ribeiro 2ORCID andMaria Raposo 2,*ORCID 1 CEFITEC, Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal 2 Laboratory 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, Portugal 3 Institute of Chemical and Biological Technology (ITQB NOVA), The New University of Lisbon, 2780-157 Oeiras, Portugal 4 Department of Chemistry, UiT—The Arctic University of Norway, N-9037 Tromsø, Norway * Author to whom correspondence should be addressed. Nanomaterials 2023, 13(10), 1613; https://doi.org/10.3390/nano13101613 Received: 4 April 2023 / Revised: 7 May 2023 / Accepted: 9 May 2023 / Published: 11 May 2023 (This article belongs to the Special Issue Application of Lipid Nanoparticles in Drug and Gene Delivery) Download Browse Figures Review Reports Versions Notes Abstract 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.