Understanding molecular mechanisms of biologics drug delivery and stability from NMR spectroscopy

Phyo, Pyae; Zhao, Xi; Templeton, Allen C.; Xu, Wei; Cheung, Jason K.; Su, Yongchao

doi:10.1016/j.addr.2021.02.007

Cited by 45 publications

(31 citation statements)

References 238 publications

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“…The derivatives that link up amphipathic constituents in ionizable cationic lipids are generally made of amide, ether, or ester, to which ester linkers being preferred due to its biodegradability. Patisiran ((ONPATTRO™), the very first FDA-approved siRNA preparation encapsulating in lipid nanoparticles, contains ionizable cationic lipids with ester linkages ( Phyo et al., 2021 ). Cationic liposomes have a high biocompatibility and can pass the cell membrane to target specific genes.…”

Section: Carrier Systems For Co-delivery Of Chemotherapeutic Agents A...mentioning

confidence: 99%

New paradigm in combination therapy of siRNA with chemotherapeutic drugs for effective cancer therapy

Kumar

Rani

Mishra

et al. 2022

Current Research in Pharmacology and Drug Discovery

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Section: Carrier Systems For Co-delivery Of Chemotherapeutic Agents A...mentioning

confidence: 99%

New paradigm in combination therapy of siRNA with chemotherapeutic drugs for effective cancer therapy

Kumar

Rani

Mishra

et al. 2022

Current Research in Pharmacology and Drug Discovery

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“…This study intends to investigate the stability of a-DLM by identifying its degradation products in a solvent system mimicking a water-based paint (i.e., slightly alkaline and containing about 20% of water). Nuclear Magnetic Resonance (NMR) spectroscopy was selected as the main analytical technique for carrying out the study, as no sample pretreatment is needed for the analysis, and information on the molecular alterations caused by degradation processes can be easily obtained [35,36]. NMR spectroscopy allowed identifying and quantifying the different by-products developed overtime and elucidating the degradation mechanisms related to their formation.…”

Section: Namementioning

confidence: 99%

New Insights into the Degradation Path of Deltamethrin

Aiello

Simons²,

Velde³

et al. 2021

Molecules

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Pyrethroids are among the insecticidal compounds indicated by the World Health Organization for mitigation of vector-borne diseases. Active deltamethrin (with chiral configuration α-S,1-R-cis) is one of the most effective pyrethroids characterized by low toxicity to humans, and it is currently tested as active ingredient for insecticidal paints. Nevertheless, several degradation processes can occur and affect the insecticidal efficacy in the complex paint matrix. In the present study, a detailed NMR analysis of deltamethrin stability has been carried out under stress conditions, mimicking a water-based insecticidal paint environment. Two novel by-products, having a diastereomeric relationship, were identified and their structure was elucidated by combining NMR, HPLC, GC-MS, and ESI-MS analyses. These compounds are the result from a nucleophilic addition involving deltamethrin and one of its major degradation products, 3-phenoxybenzaldehyde. Given the known toxicity of the aldehyde, this reaction could represent a way to reduce its concentration into the matrix. On the other hand, the toxicology of these compounds towards humans should be addressed, as their presence may adversely affect the performance of deltamethrin-containing products.

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“…16−19 Recently, the potential of both ssNMR and liquid-state NMR was illustrated for drug delivery applications to biologics. 20 Surprisingly, the number of liquid-state NMR studies carried out on drug-loaded liposomes, and more generally on drug delivery systems, is still limited. 21−31 We therefore aimed in this study to illustrate the versatility of liquid-state NMR spectroscopy to characterize various facets of liposome-peptide formulation: liposome and peptide structures, their mutual interactions, stability of the formulation, and peptide release properties upon heating.…”

Section: Introductionmentioning

confidence: 99%

“…Optimizing liposome structure and drug release properties requires advanced analytical and structural techniques. − Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to probe the structure and dynamics of virtually all types of molecules at atomic resolution, in liquid and condensed states. Solid-state NMR (ssNMR) is well-recognized for characterizing lipid systems and deciphering the mode of action of membrane-active peptides. − ssNMR has been utilized to investigate nanoparticle- as well as lipid-based drug delivery systems. − Recently, the potential of both ssNMR and liquid-state NMR was illustrated for drug delivery applications to biologics . Surprisingly, the number of liquid-state NMR studies carried out on drug-loaded liposomes, and more generally on drug delivery systems, is still limited. − We therefore aimed in this study to illustrate the versatility of liquid-state NMR spectroscopy to characterize various facets of liposome-peptide formulation: liposome and peptide structures, their mutual interactions, stability of the formulation, and peptide release properties upon heating.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Magnetic Resonance Spectroscopy: A Multifaceted Toolbox to Probe Structure, Dynamics, Interactions, and Real-Time In Situ Release Kinetics in Peptide-Liposome Formulations

et al. 2021

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Liposomal formulations represent attractive biocompatible and tunable drug delivery systems for peptide drugs. Among the tools to analyze their physicochemical properties, nuclear magnetic resonance (NMR) spectroscopy, despite being an obligatory technique to characterize molecular structure and dynamics in chemistry as well as in structural biology, yet appears to be rather sparsely used to study drug-liposome formulations. In this work, we exploited several facets of liquid-state NMR spectroscopy to characterize liposomal delivery systems for the apelin-derived K14P peptide and K14P modified by Nα-fatty acylation. Various liposome compositions and preparation modes were analyzed. Using NMR, in combination with cryo-electron microscopy and dynamic light scattering, we determined structural, dynamic, and self-association properties of these peptides in solution and probed their interactions with liposomes. Using 31P and 1H NMR, we characterized membrane fluidity and thermotropic phase transitions in empty and loaded liposomes. Based on diffusion and 1H NMR experiments, we localized and quantified peptides with respect to the interior/exterior of liposomes and changes over time and upon thermal treatments. Finally, we assessed the release kinetics of several solutes and compared various formulations. Taken together, this work shows that NMR has the potential to assist the design of peptide/liposome systems and more generally drug delivery systems.

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Understanding molecular mechanisms of biologics drug delivery and stability from NMR spectroscopy

Cited by 45 publications

References 238 publications

New paradigm in combination therapy of siRNA with chemotherapeutic drugs for effective cancer therapy

New paradigm in combination therapy of siRNA with chemotherapeutic drugs for effective cancer therapy

New Insights into the Degradation Path of Deltamethrin

Nuclear Magnetic Resonance Spectroscopy: A Multifaceted Toolbox to Probe Structure, Dynamics, Interactions, and Real-Time In Situ Release Kinetics in Peptide-Liposome Formulations

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