Abstract
Investigation of new materials for biomedical applications has represented a relevant subject in the latest decade, enhancing versatile properties of lipids. It has been documented that the capabilities of lipid-based systems improve when they combine with polymers, proteins, and sugars. In this field, understanding the driving forces behind such hybrid systems is mandatory for biomedical applications. From this perspective, it is crucial to investigate the biophysical properties of this kind of material. Here, we investigate the biophysical properties of hybrid membranes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol, and octyl-β-D-glucopyranoside (OGP). Lipid/sugar materials could have potential properties to use as nanovesicles for drug delivery. We encapsulate ibuprofen in lipid/sugar vesicles and evaluate their thermodynamics, hydrodynamics, and morphological properties by differential scanning calorimetry, dynamic light scattering, and scanning electron microscopy. We found that OGP combined with cholesterol modifies thermodynamic parameters of membranes such as phase transition temperature, enthalpy change, and cooperativity. Lipid vesicles containing OGP at 6.0 mM loaded with ibuprofen demonstrated good stability after 3 months of storage. Furthermore, electronic microscopy revealed the presence of well-defined liposomes. We conclude that cholesterol and OGP can act synergistically in polar–nonpolar spaces of the DPPC bilayer, where the hydrophobic nature of ibuprofen leads to incorporation into this hybrid core, which implies changes in the fluidity and compactness of the membrane occurring at temperatures of biological relevance. This investigation provides crucial knowledge regarding the biophysical properties of thermo-responsive biohybrid vesicles potentially to use in nanomedicine, which could be of practical reference for designing innovative drug delivery systems.
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Abbreviations
- LUV:
-
Large unilamellar vesicles
- T m :
-
Phase transition temperature
- C p :
-
Specific heat capacity at constant pressure
- ∆H m :
-
Molar enthalpy change
- ΔT 1/2 :
-
The width of the transition at half peak height
- DPPC:
-
1,2-Dipalmitoyl-sn-glycero-3-phosphocholine
- OGP:
-
Octyl-β-D-glucopyranoside
- Ibu:
-
Ibuprofen
- Chol:
-
Cholesterol
- DSC:
-
Differential scanning calorimetry
- DLS:
-
Dynamic light scattering
- SEM:
-
Scanning electron microscopy
References
Allen TM, Cullis PR. Liposomal drug delivery systems: From concept to clinical applications. Adv Drug Deliv Rev. 2013;65:36–48. https://doi.org/10.1016/j.addr.2012.09.037.
Shah S, Dhawan V, Holm R, Nagarsenker MS, Perrie Y. Liposomes: advancements and innovation in the manufacturing process. Adv Drug Deliv Rev. 2020;154–155:102–22. https://doi.org/10.1016/j.addr.2020.07.002.
Reichmuth AM, Oberli MA, Jeklenec A, Langer R, Blankschtein D. mRNA vaccine delivery using lipid nanoparticles. Ther Deliv. 2016;7(5):319–34. https://doi.org/10.4155/tde-2016-0006.
Cheng R, Liu L, Xiang Y, Lu Y, Deng L, Zhang H, Santos HA, Cui W. Advanced liposome-loaded scaffolds for therapeutic and tissue engineering applications. Biomaterials. 2020;232: 119706. https://doi.org/10.1016/j.biomaterials.2019.119706.
Róg T, Girych M, Bunker A. Mechanistic understanding from molecular dynamics in pharmaceutical research 2: lipid membrane in drug design. Pharmaceuticals. 2021;14(10):1062. https://doi.org/10.3390/ph14101062.
Gaber M, Medhat W, Hany M, Saher N, Fang JY, Elzoghby A. Protein-lipid nanohybrids as emerging platforms for drug and gene delivery: challenges and outcomes. J Control Release. 2017;254:75–91. https://doi.org/10.1016/j.jconrel.2017.03.392.
Meyer CE, Abram SL, Craciun I, Palivan CG. Biomolecule-polymer hybrid compartments: combining the best of both worlds. Phys Chem Chem Phys. 2020;22:11197–218. https://doi.org/10.1039/d0cp00693a.
Jash A, Ubeyitogullari A, Rizvi SSH. Liposomes for oral delivery of protein and peptide-based therapeutics: challenges, formulation strategies, and advances. J Mater Chem B. 2021;9:4773–92. https://doi.org/10.1039/d1tb00126d.
Kumar M, Jha A, Bharti K, Parmar G, Mishra B. Advances in lipid-based pulmonary nanomedicine for the management of inflammatory lung disorders. Nanomedicine. 2022;17(12):913–34. https://doi.org/10.2217/nnm-2021-0389.
Pérez-Isidoro R, Ruiz-Suárez JC. Thermal behavior of a lipid-protein membrane model and the effects produced by anesthetics and neurotransmitters. BBA -Biomembranes. 2020;1862(2): 183099. https://doi.org/10.1016/j.bbamem.2019.183099.
Pérez-Isidoro R, Guevara-Pantoja FJ, Ventura-Hunter C, Guerrero-Sánchez C, Ruiz-Suárez JC, Schubert US, Saldívar-Guerra E. Fluidized or not fluidized? Biophysical characterization of biohybrid lipid/protein/polymer liposomes and their interaction with tetracaine. Biochim Biophys Acta - Gen Subj. 2023;1867(2): 130287. https://doi.org/10.1016/j.bbagen.2022.130287.
Balestri A, Lonetti B, Harrisson S, Farias-Mancilla B, Zhang J, Amenitsch H, Schubert US, Guerrero-Sanchez C, Montis C, Berti D. Thermo-responsive lipophilic NIPAM-based block copolymers as stabilizers for lipid-based cubic nanoparticles. Colloids Surfaces B Biointerfaces. 2022;220: 112884. https://doi.org/10.1016/j.colsurfb.2022.112884.
Wenk MR, Alt T, Seelig A, Seelig J. Octyl-β-D-glucopyranoside partitioning into lipid bilayers: Thermodynamics of binding and structural changes of the bilayer. Biophys J. 1997;72(4):1719–31. https://doi.org/10.1016/S0006-3495(97)78818-0.
Krawczyk J. Temperature impact on the water-air interfacial activity of n-octyl and n-dodecyl-β-D-glucopyranosides. Colloids Surfaces A. 2017;533:61–7. https://doi.org/10.1016/j.colsurfa.2017.08.015.
Wang Y, Wang S, Liu Z, Ma R, Sun Q, Liu A, Yang L, Gong J, Guo X. The formation of structure I hydrate in presence of n-octyl-β-D-glucopyranoside. Fluid Phase Equilib. 2022;556: 113373. https://doi.org/10.1016/j.fluid.2021.113373.
Watanabe Y, Inoko Y. Reassembly of an integral oligomeric membrane protein OmpF porin in n-octyl β-D-glucopyranoside-lipids mixtures. Protein J. 2009;28:66–73. https://doi.org/10.1007/s10930-009-9165-4.
Krylova OO, Jahnke N, Keller S. Membrane solubilisation and reconstitution by octylglucoside: comparison of synthetic lipid and natural lipid extract by isothermal titration calorimetry. Biophys Chem. 2010;150(1–3):105–11. https://doi.org/10.1016/j.bpc.2010.03.013.
Dinesh M, Deepika S, HarishKumar R, Selvaraj CI, Roopan SM. Evaluation of Octyl-β-D-glucopyranoside (OGP) for cytotoxic, hemolytic, thrombolytic, and antibacterial activity. Appl Biochem Biotechnol. 2018;185:450–63. https://doi.org/10.1007/s12010-017-2661-7.
Zdarta A, Pacholak A, Smułek W, Zgoła-Grześkowiak A, Ferlin N, Bil A, Kovensky J, Grand E, Kaczorek E. Biological impact of octyl D-glucopyranoside based surfactants. Chemosphere. 2019;217:567–75. https://doi.org/10.1016/j.chemosphere.2018.11.025.
Hill K, LeHen-Ferrenbach C. Sugar-Based Surfactants for consumer products and technical applications. In: Ruiz CC, editor. Sugar-based surfactants: fundamentals and applications. 1st ed. Spain: CRC Press; 2008. p. 1–20. https://doi.org/10.1201/9781420051674.
Medeiros M, Marcos X, Velasco-Medina AA, Perez-Casas S, Gracia-Fadrique J. Micellization and adsorption modeling of single and mixed nonionic surfactants. Colloids Surf A Physicochem Eng Asp. 2018;556:81–92. https://doi.org/10.1016/j.colsurfa.2018.08.005.
Villegas-Pañeda X, Pérez-Casas S, Hernández-Baltazar E, Chávez-Castellanos AE. Study of interactions between octyl-β-D-glucopyranoside and the hydroxyethyl-cellulose biopolymer in aqueous solution. J Chem Thermodyn. 2014;79:69–75. https://doi.org/10.1016/j.jct.2014.06.026.
Heerklotz H. Interactions of surfactants with lipid membranes. Q Rev Biophys. 2008;41(3–4):205–64. https://doi.org/10.1017/S0033583508004721.
Kazi KM, Mandal AS, Biswas N, Guha A, Chatterjee S, Behera M, Kuotsu K. Niosome : a future of targeted drug delivery systems. J Adv Pharm Technol Res. 2010;1(4):374–80. https://doi.org/10.4103/0110-5558.76435.
Muzzalupo R, Tavano L, La Mesa C. Alkyl glucopyranoside-based niosomes containing methotrexate for pharmaceutical applications : evaluation of physico-chemical and biological properties. Int J Pharm. 2013;458(1):224–9. https://doi.org/10.1016/j.ijpharm.2013.09.011.
Róg T, Vattulainen I. Cholesterol, sphingolipids, and glycolipids: what do we know about their role in raft-like membranes? Chem Phys Lipids. 2014;184:82–104. https://doi.org/10.1016/j.chemphyslip.2014.10.004.
Regen SL. Cholesterol’s condensing effect: unpacking a century-old mystery. JACS Au. 2022;2(1):84–91. https://doi.org/10.1021/jacsau.1c00493.
Pozzi D, Marchini C, Cardarelli F, Amenitsch H, Garulli C, Bifone A, Caracciolo G. Transfection efficiency boost of cholesterol-containing lipoplexes. BBA - Biomembr. 2012;1818(9):2335–43. https://doi.org/10.1016/j.bbamem.2012.05.017.
Simons K, Ikonen E. Functional rafts in cell membranes. Nature. 1997;387:569–72. https://doi.org/10.1038/42408.
Regen SL. The origin of lipid rafts. Biochemistry. 2020;59(49):4617–21. https://doi.org/10.1021/acs.biochem.0c00851.
Jackson ML, Schmidt CF, Lichtenberg D, Litman BJ, Albert AD. Solubilization of phosphatidylcholine bilayers by octyl glucoside. Biochemistry. 1982;21(19):4576–82. https://doi.org/10.1021/bi00262a010.
Ollivon M, Eidelman O, Blumenthal R, Walter A. Micelle-vesicle transition of egg phosphatidylcholine and octylglucoside. Biochemistry. 1988;27(5):1695–703. https://doi.org/10.1021/bi00405a047.
Almog S, Litman BJ, Wimley W, Cohen J, Wachtel EJ, Barenholz Y, Ben-Shaul A, Lichtenberg D. States of aggregation and phase transformations in mixtures of phosphatidylcholine and octyl glucoside. Biochemistry. 1990;29(19):4582–92. https://doi.org/10.1021/bi00471a012.
Eidelman O, Blumenthal R, Walter A. Composition of octyl glucoside-phosphatidylcholine mixed micelles. Biochemistry. 1988;27(8):2839–46. https://doi.org/10.1021/bi00408a027.
Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 2009;17:275–342. https://doi.org/10.1007/s10787-009-0016-x.
Bushra R, Aslam N. An overview of clinical pharmacology of ibuprofen. Oman Med J. 2010;25(3):155–61. https://doi.org/10.5001/omj.2010.49.
Lanas A, Hunt R. Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits and risks of therapeutic strategies. Ann Med. 2006;38(6):415–28. https://doi.org/10.1080/07853890600925843.
Seifert SA, Bronstein AC, McGuire T. Massive ibuprofen ingestion with survival. J Toxicol - Clin Toxicol. 2000;38(1):55–7. https://doi.org/10.1081/CLT-100100917.
Hawkey CJ. COX-1 and COX-2 inhibitors. Best Pract Res Clin Gastroenterol. 2001;15(5):801–20. https://doi.org/10.1053/bega.2001.0236.
Aloi E, Rizzuti B, Guzzi R, Bartucci R. Association of ibuprofen at the polar / apolar interface of lipid membranes. Arch Biochem Biophys. 2018;654:77–84. https://doi.org/10.1016/j.abb.2018.07.013.
Lygre H, Moe G, Holmsen H. Interaction of ibuprofen with eukaryotic membrane lipids. Acta Odontol Scand. 2003;61:303–9. https://doi.org/10.1080/00016350310006555.
Heimburg T. Lipid melting. In: Heimburg T, editor. Thermal Biophysics of Membranes. 1st ed. Germany: Wiley; 2007. p. 75–97. https://doi.org/10.1002/9783527611591.ch6.
Lewis RNAH, Mannock DA, McElhaney RN. Differential Scanning Calorimetry in the Study of Lipid Phase Transitions in Model and Biological Membranes. In: Dopico AM, editor. Methods in Membrane Lipids. Methods in Molecular Biology. New Jersey: Humana Press; 2007. p. 171–95. https://doi.org/10.1007/978-1-59745-519-0_12.
Raudino A, Sarpietro MG, Pannuzzo M. Differential scanning calorimetry (DSC): theoretical fundamentals. In: Pignatello R, editor. Drug-Biomembrane Interaction Studies. The application of Calorimetric techniques. 1st ed. UK: Woodhead Publishing; 2013. p. 127–68. https://doi.org/10.1533/9781908818348.127.
Sugár IP. Cooperativity and classification of phase transitions. Application to one- and two-component phospholipid membranes. J Phys Chem. 1987;91(1):95–101. https://doi.org/10.1021/j100285a023.
Mason PC, Gaulin BD, Epand RM, Wignall GD, Lin JS. Small angle neutron scattering and calorimetric studies of large unilamellar vesicles of the phospholipid dipalmitoylphosphatidylcholine. Phys Rev E. 1999;59:3361–7. https://doi.org/10.1103/PhysRevE.59.3361.
Kreutzberger MA, Tejada E, Wang Y, Almeida PF. GUVs Melt like LUVs: the large heat capacity of MLVs is not due to large size or small curvature. Biophys J. 2015;108(11):2619–22. https://doi.org/10.1016/j.bpj.2015.04.034.
Khajeh A, Modarress H. The influence of cholesterol on interactions and dynamics of ibuprofen in a lipid bilayer. BBA - Biomembr. 2014;1838(10):2431–8. https://doi.org/10.1016/j.bbamem.2014.05.029.
Bennett WFD, MacCallum JL, Tieleman DP. Thermodynamic analysis of the effect of cholesterol on dipalmitoylphosphatidylcholine lipid membranes. J Am Chem Soc. 2009;131(5):1972–8. https://doi.org/10.1021/ja808541r.
Falck E, Patra M, Karttunen M, Hyvönen MT, Vattulainen I. Lessons of slicing membranes: interplay of packing, free area, and lateral diffusion in phospholipid/cholesterol bilayers. Biophys J. 2004;87(2):1076–91. https://doi.org/10.1529/biophysj.104.041368.
Almeida PF, Carter FE, Kilgour KM, Raymonda MH, Tejada E. Heat capacity of DPPC/cholesterol mixtures: comparison of single bilayers with multibilayers and simulations. Langmuir. 2018;34(33):9798–809. https://doi.org/10.1021/acs.langmuir.8b01774.
Mannock DA, Lewis RNAH, McElhaney RN. Comparative calorimetric and spectroscopic studies of the effects of lanosterol and cholesterol on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes. Biophys J. 2006;91(1):3327–40. https://doi.org/10.1529/biophysj.106.084368.
McMullen TPW, McElhaney RN. New aspects of the interaction of cholesterol with dipalmitoylphosphatidylcholine bilayers as revealed by high-sensitivity differential scanning calorimetry. Biochim Biophys Acta. 1995;1234(1):90–8. https://doi.org/10.1016/0005-2736(94)00266-r.
Alsop RJ, Armstrong CL, Maqbool A, Toppozini L, Dies H, Rheinstädter MC. Cholesterol expels ibuprofen from the hydrophobic membrane core and stabilizes lamellar phases in lipid membranes containing ibuprofen. Soft Matter. 2015;11:4756–67. https://doi.org/10.1039/c5sm00597c.
Newville M, Stensitzki T, Allen DB, Rawlik M, Ingargiola A. LMFIT: Non-linear least-square minimization and curve-fitting for Python (1.0.2). Zenodo. 2021. https://doi.org/10.5281/zenodo.11813.
Uria-Canseco E, Perez-Casas S. Spherical and tubular dimyristoylphosphatidylcholine liposomes: phase transition induced by pinocembrin. J Therm Anal Calorim. 2020;139:399–409. https://doi.org/10.1007/s10973-019-08416-0.
Yonar D, Sünnetçioǧlu MM. Spectroscopic and calorimetric studies on trazodone hydrochloride- phosphatidylcholine liposome interactions in the presence and absence of cholesterol. BBA - Biomembr. 2014;1838:2369–79. https://doi.org/10.1016/j.bbamem.2014.06.009.
Bibi S, Kaur R, Henriksen-Lacey M, Mcneil SE, Wilkhu J, Lattmann E, Christensen D, Mohammed AR, Perrie Y. Microscopy imaging of liposomes : from coverslips to environmental SEM. Int J Pharm. 2011;417(1–2):138–50. https://doi.org/10.1016/j.ijpharm.2010.12.021.
Ruozi B, Belletti D, Tombesi A, Tosi G, Bondioli L, Forni F, Vandelli MA. AFM, ESEM, TEM, and CLSM in liposomal characterization : a comparative study. Int J Nanomed. 2011;6:557–63. https://doi.org/10.2147/IJN.S14615.
Hung WC, Lee MT, Chen FY, Huang HW. The condensing effect of cholesterol in lipid bilayers. Biophys J. 2007;92(11):3960–7. https://doi.org/10.1529/biophysj.106.099234.
Javanainen M, Martinez-Seara H, Vattulainen I. Nanoscale membrane domain formation driven by cholesterol. Sci Rep. 2017;7(1143):1–10. https://doi.org/10.1038/s41598-017-01247-9.
Acknowledgements
RP-I thanks DGAPA-UNAM for a postdoctoral scholarship and acknowledges CONAHCYT—México for supporting in part the writing of this work via a postdoctoral fellowship, project number 3969865. This work was supported by FQ-UNAM (PAIP 5000-9020). We thank Rafael Ivan Puente Lee from USAII-UNAM for his competent assistance in SEM and Dr. Ismael Bustos Jaimes for the use of his Zetasizer equipment.
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RP-I, SP-C, and AJD-S helped in conceptualization; RP-I and AJD-S helped in methodology and data analysis; RP-I and AJD-S helped in original draft preparation; RP-I, SP-C, and AJD-S contributed to review and editing; and RP-I, SP-C, and AJD-S worked in resources. All authors have read and agreed to the published version of the manuscript.
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Díaz-Salazar, A.J., Pérez-Casas, S. & Pérez-Isidoro, R. Hybrid liposomes of DPPC/cholesterol/octyl-β-D-glucopyranoside with/without ibuprofen: thermal and morphological study. J Therm Anal Calorim 148, 13983–13994 (2023). https://doi.org/10.1007/s10973-023-12704-1
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DOI: https://doi.org/10.1007/s10973-023-12704-1