Synthesis and Characterization of Novel Amphiphilic -Benzyl 1,4-Dihydropyridine Derivatives-Evaluation of Lipid Monolayer and Self-Assembling Properties

Overview

Journal Materials (Basel)

Publisher MDPI

Date 2023 Jun 28

PMID 37374390

Authors

Anna Krapivina

Davis Lacis

Martins Rucins

Mara Plotniece

Karlis Pajuste

Arkadij Sobolev

Aiva Plotniece

Affiliations

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Abstract

Liposomes and other nanoparticles have been widely studied as innovative nanomaterials because of their unique properties. Pyridinium salts, on the basis of 1,4-dihydropyridine (1,4-DHP) core, have gained significant attention due to their self-assembling properties and DNA delivery activity. This study aimed to synthesize and characterize original -benzyl substituted 1,4-dihydropyridines and evaluate the influence on structure modifications on compound physicochemical and self-assembling properties. Studies of monolayers composed of 1,4-DHP amphiphiles revealed that the mean molecular areas values were dependent on the compound structure. Therefore, the introduction of -benzyl substituent to the 1,4-DHP ring enlarged the mean molecular area by almost half. All nanoparticle samples obtained by ethanol injection method possessed positive surface charge and average diameter of 395-2570 nm. The structure of the cationic head-group affects the size of the formed nanoparticles. The diameter of lipoplexes formed by 1,4-DHP amphiphiles and mRNA at nitrogen/phosphate (N/P) charge ratios of 1, 2, and 5 were in the range of 139-2959 nm and were related to the structure of compound and N/P charge ratio. The preliminary results indicated that more prospective combination are the lipoplexes formed by pyridinium moieties containing -unsubstituted 1,4-DHP amphiphile and pyridinium or substituted pyridinium moieties containing -benzyl 1,4-DHP amphiphiles - at N/P charge ratio of 5, which would be good candidates for potential application in gene therapy.

Citing Articles

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References

Nikolova M, Kumar E, Chavali M . Updates on Responsive Drug Delivery Based on Liposome Vehicles for Cancer Treatment. Pharmaceutics. 2022; 14(10). PMC: 9608678. DOI: 10.3390/pharmaceutics14102195. View

van der Koog L, Gandek T, Nagelkerke A . Liposomes and Extracellular Vesicles as Drug Delivery Systems: A Comparison of Composition, Pharmacokinetics, and Functionalization. Adv Healthc Mater. 2021; 11(5):e2100639. PMC: 11468589. DOI: 10.1002/adhm.202100639. View

Soprano E, Polo E, Pelaz B, Del Pino P . Biomimetic cell-derived nanocarriers in cancer research. J Nanobiotechnology. 2022; 20(1):538. PMC: 9771790. DOI: 10.1186/s12951-022-01748-4. View

Apsite G, Timofejeva I, Vezane A, Vigante B, Rucins M, Sobolev A . Synthesis and Comparative Evaluation of Novel Cationic Amphiphile C12-Man-Q as an Efficient DNA Delivery Agent In Vitro. Molecules. 2018; 23(7). PMC: 6100083. DOI: 10.3390/molecules23071540. View

Petrichenko O, Plotniece A, Pajuste K, Rucins M, Dimitrijevs P, Sobolev A . Evaluation of Physicochemical Properties of Amphiphilic 1,4-Dihydropyridines and Preparation of Magnetoliposomes. Nanomaterials (Basel). 2021; 11(3). PMC: 7996955. DOI: 10.3390/nano11030593. View

Lombardo D, Kiselev M . Methods of Liposomes Preparation: Formation and Control Factors of Versatile Nanocarriers for Biomedical and Nanomedicine Application. Pharmaceutics. 2022; 14(3). PMC: 8955843. DOI: 10.3390/pharmaceutics14030543. View

Sturm L, Poklar Ulrih N . Basic Methods for Preparation of Liposomes and Studying Their Interactions with Different Compounds, with the Emphasis on Polyphenols. Int J Mol Sci. 2021; 22(12). PMC: 8234105. DOI: 10.3390/ijms22126547. View

Petrichenko O, Rucins M, Vezane A, Timofejeva I, Sobolev A, Cekavicus B . Studies of the physicochemical and structural properties of self-assembling cationic pyridine derivatives as gene delivery agents. Chem Phys Lipids. 2015; 191:25-37. DOI: 10.1016/j.chemphyslip.2015.08.005. View

Mathaes R, Winter G, Besheer A, Engert J . Non-spherical micro- and nanoparticles: fabrication, characterization and drug delivery applications. Expert Opin Drug Deliv. 2014; 12(3):481-92. DOI: 10.1517/17425247.2015.963055. View

10.

Niemirowicz-Laskowska K, Gluszek K, Piktel E, Pajuste K, Durnas B, Krol G . Bactericidal and immunomodulatory properties of magnetic nanoparticles functionalized by 1,4-dihydropyridines. Int J Nanomedicine. 2018; 13:3411-3424. PMC: 6001743. DOI: 10.2147/IJN.S157564. View

11.

Triggle D . The 1,4-dihydropyridine nucleus: a pharmacophoric template part 1. Actions at ion channels. Mini Rev Med Chem. 2003; 3(3):215-23. DOI: 10.2174/1389557033488141. View

12.

Liu P, Chen G, Zhang J . A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives. Molecules. 2022; 27(4). PMC: 8879473. DOI: 10.3390/molecules27041372. View

13.

Felice B, Prabhakaran M, Rodriguez A, Ramakrishna S . Drug delivery vehicles on a nano-engineering perspective. Mater Sci Eng C Mater Biol Appl. 2014; 41:178-95. DOI: 10.1016/j.msec.2014.04.049. View

14.

Yusuf A, Almotairy A, Henidi H, Alshehri O, Aldughaim M . Nanoparticles as Drug Delivery Systems: A Review of the Implication of Nanoparticles' Physicochemical Properties on Responses in Biological Systems. Polymers (Basel). 2023; 15(7). PMC: 10096782. DOI: 10.3390/polym15071596. View

15.

Jurak M, Szafran K, Cea P, Martin S . Analysis of Molecular Interactions between Components in Phospholipid-Immunosuppressant-Antioxidant Mixed Langmuir Films. Langmuir. 2021; 37(18):5601-5616. PMC: 8280729. DOI: 10.1021/acs.langmuir.1c00434. View

16.

Perinelli D, Cespi M, Lorusso N, Palmieri G, Bonacucina G, Blasi P . Surfactant Self-Assembling and Critical Micelle Concentration: One Approach Fits All?. Langmuir. 2020; 36(21):5745-5753. PMC: 8007100. DOI: 10.1021/acs.langmuir.0c00420. View

17.

Gindy M, Feuston B, Glass A, Arrington L, Haas R, Schariter J . Stabilization of Ostwald ripening in low molecular weight amino lipid nanoparticles for systemic delivery of siRNA therapeutics. Mol Pharm. 2014; 11(11):4143-53. DOI: 10.1021/mp500367k. View

18.

Jaafar-Maalej C, Diab R, Andrieu V, Elaissari A, Fessi H . Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation. J Liposome Res. 2009; 20(3):228-43. DOI: 10.3109/08982100903347923. View

19.

Wang N, Wang T, Li T, Deng Y . Modulation of the physicochemical state of interior agents to prepare controlled release liposomes. Colloids Surf B Biointerfaces. 2009; 69(2):232-8. DOI: 10.1016/j.colsurfb.2008.11.033. View

20.

Dhiman N, Awasthi R, Sharma B, Kharkwal H, Kulkarni G . Lipid Nanoparticles as Carriers for Bioactive Delivery. Front Chem. 2021; 9:580118. PMC: 8107723. DOI: 10.3389/fchem.2021.580118. View