Abstract
In this study, we investigate the thermotropic effects of diblock copolymer poly(N-isopropylacrylamide)-block-poly(acrylic acid) (PNIPAM-b-PAA) on fully hydrated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers and its ability to alter the membranes’ organization, fluidity and phase behavior. The composition of the diblock copolymer and the nature of dispersion medium (pH and ionic strength) were also examined. For these purposes, pure DPPC lipid and polymer–lipid mixed systems, hydrated in three different dispersion media (i.e., HPLC-grade water, phosphate buffer saline and hydrochloric acid solution of pH 4.5), were investigated by differential scanning calorimetry. Two compositions of PNIPAM-b-PAA with different molar ratio of the polymeric blocks were used. PNIPAM-b-PAA presents great scientific interest due to the combination of the special characteristics of its homopolymer components; it is dual responsive both in temperature and in pH changes. The incorporation of the PNIPAM-b-PAA into the DPPC bilayers causes particularly significant perturbations in their thermotropic behavior, slightly different in each dispersion medium. The results indicated the ordering of the polymer guest near the polar head group surface probably by its PAA block and, on the other hand, the penetration of the PNIPAM block into the hydrophobic bilayer core, causing membrane disruption in a temperature-depended manner. We can conclude that the lipid–polymer interactions seem to be affected by the pH and the ionic strength of the hydration medium, as well as the polymer content incorporated in the DPPC bilayer. These studies could be a roadmap in order to rationally design and develop chimeric liposomes.
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Abbreviations
- PNIPAM-b-PAA:
-
Poly(N-isopropylacrylamide)-block-poly(acrylic acid)
- DPPC:
-
1,2-Dipalmitoyl-sn-glycero-3-phosphocholine
- PBS:
-
Phosphate buffer saline
- DSC:
-
Differential scanning calorimetry
- LCST:
-
Lower critical solution temperature
References
Pippa N, Merkouraki M, Pispas S, Demetzos C. DPPC:MPOx chimeric advanced drug delivery nanosystems (chi-aDDnSs): physicochemical and structural characterization, stability and drug release studies. Int J Pharm. 2013;450(1–2):1–10.
Pippa N, Kaditi E, Pispas S, Demetzos C. PEO-b-PCL–DPPC chimeric nanocarriers: self-assembly aspects in aqueous and biological media and drug incorporation. Soft Matter. 2013;9(15):4073–82.
Pippa N, Pispas S, Demetzos C. The metastable phases as modulators of biophysical behavior of liposomal membranes. J Therm Anal Calorim. 2015;120(1):937–45.
Gardikis K, Tsimplouli C, Dimas K, Micha-Screttas M, Demetzos C. New chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) as doxorubicin carriers. Int J Pharm. 2010;402(1–2):231–7.
Kontogiannopoulos KN, Assimopouloua AN, Hatziantoniou S, Karatasos K, Demetzos C, Papageorgiou VP. Chimeric advanced drug delivery nano systems (chi-aDDnSs) for shikonin combining dendritic and liposomal technology. Int J Pharm. 2012;422(1–2):381–9.
Kono K, Nakaib R, Morimotob K, Takagishia T. Thermosensitive polymer-modified liposomes that release contents around physiological temperature. Biochim Biophys Acta. 1999;1416(1–2):239–50.
Kono K, Ozawaa T, Yoshidab T, Ozakia F, Ishizakac Y, Maruyamad K, Kojimae C, Haradaa A, Aoshimab S. Highly temperature-sensitive liposomes based on a thermosensitive block copolymer for tumor-specific chemotherapy. Biomaterials. 2010;31(27):7096–105.
Jhaveri A, Deshpande P, Torchilin V. Stimuli-sensitive nanopreparations for combination cancer therapy. J Control Release. 2014;190:352–70.
Chenga R, Menga F, Denga C, Kloka HA, Zhong Z. Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials. 2013;34(14):3647–57.
Strandman S, Zhu XX. Thermo-responsive block copolymers with multiple phase transition temperatures in aqueous solutions. Prog Polym Sci. 2015;42:154–76.
Bastakoti BP, Sudhina G, Kenichi N, Yusuke Y. Stimuli-induced core–corona inversion of micelle of poly(acrylic acid)-block-poly(N-isopropylacrylamide) and its application in drug delivery. Macromol Chem Phys. 2015;216(3):287–91.
Gil ES, Hudson SM. Stimuli-reponsive polymers and their bioconjugates. Prog Polym Sci. 2004;29:1173–222.
Ta T, Convertine AJ, Reyes CR, Stayton PS, Porter TM. Thermosensitive liposomes modified with poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers for triggered release of doxorubicin. Biomacromolecules. 2010;11(8):1915–20.
Ta T, Bartolak-Suki E, Park EJ, Karrobi K, McDannold NJ, Porter TM. Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating. J Control Release. 2014;194:71–81.
Kim JC, Bae SK, Kim JD. Temperature-sensitivity of liposomal lipid bilayers mixed with poly(N-isopropylacrylamide-co-acrylic acid). J Biochem. 1997;121(1):15–9.
Heyda J, Soll S, Yuan J, Dzubiella J. Thermodynamic description of the LCST of charged thermoresponsive copolymers. Macromolecules. 2014;47(6):2096–102.
Schild HG. Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci. 1992;17:163–249.
Lee SM, Nguyen ST. Smart nanoscale drug delivery platforms from stimuli-responsive polymers and liposomes. Macromolecules. 2013;46(23):9169–80.
Weng Y, Ding Y, Zhang G. Microcalorimetric investigation on the lower critical solution temperature behavior of N-isopropycrylamide-co-acrylic acid copolymer in aqueous solution. J PhysChem B. 2006;110(24):11813–7.
Kapou A, Nikolaropoulos S, Siapi E, Mauromoustakos T. Effects of steroidal carriers of alkylating agents on the phase transition in DPPC membrane bilayers. Thermochim Acta. 2005;429(1):53–6.
Berényi S, Mihály J, Kristyán S, Naszályi Nagy L, Telegdi J, Bóta A. Thermotropic and structural effects of poly(malic acid) on fully hydrated multilamellar DPPC-water systems. Biochim Biophys Acta. 2013;828(2):661–9.
Bonora S, Torreggianib A, Finia G. DSC and Raman study on the interaction between polychlorinated biphenyls (PCB) and phospholipid liposomes. Thermochim Acta. 2003;408(1–2):55–65.
Pantusa M, Bartucci R, Sportelli L. Calorimetric and spin-label ESR studies of PEG:2000-DPPE containing DPPC/lyso-PPC mixtures. Colloid Polym Sci. 2007;285(6):649–56.
Grasso D, Milardi D, La Rosa C, Rizzarelli E. DSC study of the interaction of the prion peptide PrP106-126 with artificial membranes. New J Chem. 2001;25(12):1543–8.
Tabbakhian M, Rogers JA. Interaction of insulin, cholesterol-derivatize dmannan, and carboxymethyl chitin with liposomes: a differential scanning calorimetry study. Res Pharm Sci. 2012;7(1):43–50.
Kenji S, Tirrell DA. pH-Dependent complexation of poly(acrylic acid) derivatives with phospholipid vesicle membranes. Macromolecules. 1984;17(9):1692–8.
Smith ΕΑ, Dea PK. Differential scanning calorimetry. Studies of phospholipid membranes: the interdigitated gel phase. In: Elkordy AA, editor. Applications of calorimetry in a wide context—differential scanning calorimetry, isothermal titration calorimetry and microcalorimetry, chapter 18. 2013. pp. 407–444.
Pippa N, Meristoudi A, Pispas S, Demetzos C. Temperature-dependent drug release from DPPC:C12H25-PNIPAM-COOH liposomes: control of the drug loading/release by modulation of the nanocarriers’ components. Int J Pharm. 2015;485(1–2):374–82.
Munavirov BV, Filippov AV, Rudakova MA, Antzutkin ON. Polyacrylic acid modifies local and lateral mobilities in lipid membranes. J Dispersion Scitechnol. 2014;35(6):848–58.
Fujiwara M, Grubbs RH, Baldeschwieler JD. Characterization of pH-dependent poly(acrylic acid) complexation with phospholipid vesicles. J Colloid Interface Sci. 1997;185(1):210–6.
Ta T, Porter TM. Thermosensitive liposomes for localized delivery and triggered release of chemotherapy. J Control Release. 2013;169(1–2):112–25.
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Kolman, I., Pippa, N., Meristoudi, A. et al. A dual-stimuli-responsive polymer into phospholipid membranes. J Therm Anal Calorim 123, 2257–2271 (2016). https://doi.org/10.1007/s10973-015-5080-4
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DOI: https://doi.org/10.1007/s10973-015-5080-4