Stability of various PLGA and lipid nanoparticles in temperature and in time and new technology for the preparation of liposomes for anticancer and antibiotic loading

  • 99 Accesses


The stabilizer, which is used during the preparation of Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), is of great importance for particle properties. It could be shown that the stabilizer affects the PLGA NPs stability in time and in dependence of temperature, which are important parameters for their practical use. Complex nanoparticles were prepared, for which we have used tetrandrine, azithromycin, and tobramycin that were incorporated into nanoparticles of different origin—PLGA nanoparticles and DPPC/DPPA liposomes. The sizes and surface potentials of complex nanoparticles have been determined. The diameters of the obtained nanoparticles were 150–200 nm, and they had surface potentials with different charge and value (for PLGA with PL 10RS and PLGA with PL 35 are − 32.8 and − 22.5 mV, respectively, and for PLGA with DMAB + 15.0 mV). From calorimetric and spectrophotometric studies, the structural stability of complex nanoparticles with drug has been determined. The dependence on temperature and time could be shown. Structural changes of the particles in the temperature interval of 25–40 °C could be observed. It turned out that these transformations for the complex liposomes prepared with DPPC are completely reversible, and for other nanoparticles, these changes are irreversible, which means, that after phase transition, the nanoparticles internal structure restores in a different ways. Furthermore, a method, which allowed to observe the release of drugs from nanoparticles (as for PLGA, also for liposomal nanoparticles) initiated by temperature, was used. The work makes use of a new and fast technology that can be used to produce complex, drug containing liposomes in a one-step procedure.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10


  1. 1.

    Kelly C, Jefferies C, Cryan S. Targeted liposomal drug delivery to monocytes and macrophages. J Drug Deliv. 2011;1:1.

  2. 2.

    Bozzuto G, Molinari A. Liposomes as nanomedical devices. J Nanomed. 2015;10:975–99.

  3. 3.

    Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater. 2002;6:319–27.

  4. 4.

    Danhier F, Ansorena E, Silva JM, Coco R, Breton A, Préat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012;161:505–22.

  5. 5.

    Hillaireau H, Couvreur P. Nanocarriers’ entry into the cell: relevance to drug delivery. Cell Mol Life Sci. 2009;66:2873–96.

  6. 6.

    Mastrobattista E, Storm G, Bloois L, Reszka R, Bloemen P, Ceommelin D, Henricks P. Cellular uptake of liposomes targeted to intercellular adhesion molecule-1 (ICAM-1) on bronchial epithelial cells. BBA Biomembr. 1999;1419:353–61.

  7. 7.

    Voinea M, Simionescu M. Designing of ‘intelligent’ liposomes for efficient delivery of drugs. J Cell Mol Med. 2002;6:465–74.

  8. 8.

    Morilla MJ, Romero EL. Nanotoxicity of lipid-based nanomedicines. In: Rai M, Biswas J, editors. Nanomaterials: ecotoxicity, safety, and public perception. Cham: Springer; 2019. p. 133–65.

  9. 9.

    Makadia H, Siegel S. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011;3:1377–97.

  10. 10.

    Asfia S, Mohammadian M, Kouchakzadeh H. Polymeric nanoparticulates as efficient anticancer drugs delivery systems. In: Rahmandoust M, Ayatollahi M, editors. Nanomaterials for advanced biological applications. Cham: Springer; 2019. p. 55–84.

  11. 11.

    Panagi Z, Beletsi A, Evangelatos G, Livaniou E, Ithakissios DS, Avgoustakis K. Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA-mPEG nanoparticles. Int J Pharm. 2001;221:143–52.

  12. 12.

    Vasir JK, Labhasetwar V. Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev. 2007;59:718–28.

  13. 13.

    Shweta Sh, Ankush P, Shivpoojan K, Rajat S. PLGA-based nanoparticles: a new paradigm in biomedical applications. Trends Anal Chem. 2016;80:30–40.

  14. 14.

    Lakshmi P, Rajesh K, Devan U, Mahesh K, Nithya G, Antony J. Encapsulation of doxorubicin in PLGA nanoparticles enhances cancer therapy. Clin Oncol. 2017;2:1–6.

  15. 15.

    Waled H, Bezuidenhout D. Poly(lactic acid) as biomaterial for cardiovascular devices and tissue engineering applications. In: Di Lorenzo M, Androsch R, editors. Industrial applications of poly(lactic acid). Cham: Springer; 2018. p. 51–77.

  16. 16.

    Pavot V, Berthet M, Rességuier J, Legaz S, Handké N, Gilbert SC, Paul S, Verrier B. Poly(lactic acid) and poly(lactic-co-glycolic acid) particles as versatile carrier platforms for vaccine delivery. Nanomedicine. 2014;9(17):2703–18.

  17. 17.

    Zhang L, Geng Y, Duan W, Wang D, Fu M, Wang X. Ionic liquid-based ultrasound-assisted extraction of fangchinoline and tetrandrine from Stephaniae tetrandrae. J Sep Sci. 2009;32(20):3550–4.

  18. 18.

    Feng D, Mei Y, Wang Y, Zhang B, Wang C, Xu L. Tetrandrine protects mice from concanavalin A-induced hepatitis through inhibiting NF-kappaB activation. Immunol Lett. 2008;121(2):127–33.

  19. 19.

    Liu C, Gong K, Mao X, Li W. Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma. Int J Cancer. 2011;129(6):1519–31.

  20. 20.

    Cheng Z, Wang K, Wei J, Lu X, Liu B. Proteomic analysis of anti-tumor effects by tetrandrine treatment in HepG2 cells. Phytomedicine. 2010;13:1000–5.

  21. 21.

    Sakurai Y, Kolokoltsov A, Chen C, Tidwell M, Bauta W, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey R. Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science. 2015;347(6225):995–8.

  22. 22.

    Taylor SP, Sellers E, Taylor BT. Azithromycin for the prevention of COPD exacerbations: the good, bad, and ugly. Am J Med. 2015;128(12):1362.

  23. 23.

    Greenwood D. Antimicrobial drugs: chronicle of a twentieth century medical triumph. Oxford: Oxford University Press; 2008. p. 239.

  24. 24.

    Bernard DD. Mechanism of bactericidal action of aminoglycosides. Microbiol Rev. 1987;51(3):341.

  25. 25.

    Kotra LP, Haddad J, Mobashery S. Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrob Agents Chemother. 2000;44(12):3249–56.

  26. 26.

    Shi C, Ahmad KS, Wang K, Schneider M. Improved delivery of the natural anticancer drug tetrandrine. Int J Pharm. 2015;479(1):41–51.

  27. 27.

    Bhardwaj V, Ankola DD, Gupta SC, Schneider M, Lehr CM, Kumar MNVR. PLGA nanoparticles stabilized with cationic surfactant: safety studies and application in oral delivery of paclitaxel to treat chemical-induced breast cancer in rat. Pharm Res Dord. 2009;26(11):2495–503.

  28. 28.

    Shi C, Thum C, Zhang Q, Tu W, Pelaz B, Zhang Y, Schneider M. Inhibition of the cancer-associated TASK 3 channels by magnetically induced thermal release of tetrandrine from a polymeric drug carrier. J Control Release. 2016;237:50–60.

  29. 29.

    Privalov PL, Potekhin SA. Scanning microcalorimetry in studying temperature-induced changes in proteins. Methods Enzymol. 1986;131:4–51.

  30. 30.

    Pentak D, Sułkowski W, Sułkowska A. Influence of some physical properties of 5-fluorouracil on encapsulation efficiency in liposomes. J Therm Anal Calorim. 2012;108(1):67–71.

  31. 31.

    Pruchnik H, Kral T, Hof M. Lipid and DNA interaction with the triorganotin dimethylaminophenylazobenzoates studied by DSC and spectroscopy methods. J Therm Anal Calorim. 2018;134(1):691–700.

  32. 32.

    Shehata T, Ogawara K, Higaki K, Kimura T. Prolongation of residence time of liposome by surface-modification with mixture of hydrophilic polymers. Int J Pharm. 2008;359:272–9.

  33. 33.

    Mdzinarashvili T, Khvedelidze M, Shekiladze E, Machaidze R. Novel technology for the fast production of complex nanoliposomes. J Biol Phys Chem. 2016;16(4):172–6.

  34. 34.

    Shekiladze E, Mdzinarashvili T, Khvedelidze M. Calorimetric study the stability of DPPC liposomes and C and E vitamins complexes. Exp Clin Med. 2017;2:71–3.

  35. 35.

    Zhengjun Ch, Rong L, Xiaohui J. Spectroscopic studies on the interaction between tetrandrine and two serum albumins by chemometrics methods. Spectrochim Acta. 2013;115:92–105.

  36. 36.

    Khvedelidze M, Mdzinarashvili T, Shekiladze E, Schneider M, Moersdorf D, Bernhardt I. Structure of drug delivery DPPA and DPPC liposomes with ligands and their permeability through cells. J Liposome Res. 2015;25:20–31.

Download references

Author information

Correspondence to Tamaz Mdzinarashvili.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mdzinarashvili, T., Khvedelidze, M., Shekiladze, E. et al. Stability of various PLGA and lipid nanoparticles in temperature and in time and new technology for the preparation of liposomes for anticancer and antibiotic loading. J Therm Anal Calorim 139, 1131–1140 (2020) doi:10.1007/s10973-019-08451-x

Download citation


  • Thermodynamics of nanoparticles
  • PLGA particles
  • Drug in liposomes
  • DPPC
  • DPPA