Skip to main content
Log in

DSC for evaluating the encapsulation efficiency of lidocaine-loaded liposomes compared to the ultracentrifugation method

  • Published:
Journal of Thermal Analysis and Calorimetry Aims and scope Submit manuscript

Abstract

This study reports the investigation of liposomal formulations of lidocaine in the form of a free base (LID). LID was encapsulated into large multilamellar vesicles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Samples of a mass ratio of LID with respect to DMPC ranging from 1 to 10% were investigated. The effects of the increasing LID concentration on the bilayer membrane were determined in terms of size, polydispersity index, zeta potential, encapsulation efficiency (EE %) and partition coefficient. Furthermore, differential scanning calorimetry (DSC) studies were also carried out to analyze the effect of LID on the liposome phase transition temperature and to calculate the EE % with an unfrequented method. The EE % results obtained by different experimental procedures were quite ambiguous, but the DSC measurements confirmed the ultracentrifugation direct method. The calculated partition coefficients of these two methods were in good agreement, too. Our research revealed a less known application field of DSC, as a fast and reliable tool to determine EE%.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mezei M, Gulasekharam V. Liposomes-a selective drug delivery system for the topical route of administration: gel dosage form. J Pharm Pharmacol. 1982;34(7):473–4.

    Article  CAS  Google Scholar 

  2. Margalit R. Liposome-mediated drug targeting in topical and regional therapies. Crit Rev Ther Drug Carr Syst. 1995;12(2–3):233–61.

    Article  CAS  Google Scholar 

  3. Fresta M, Puglisi G. Application of liposomes as potential cutaneous drug delivery systems. In vitro and in vivo investigation with radioactively labelled vesicles. J Drug Target. 1996;4(2):95–101.

    Article  CAS  Google Scholar 

  4. Planas ME, Gonzalez P, Rodriguez L, Sanchez S, Cevc G. Noninvasive percutaneous induction of topical analgesia by a new type of drug carrier, and prolongation of local pain insensitivity by anesthetic liposomes. Anesth Analg. 1992;75(4):615–21.

    Article  CAS  Google Scholar 

  5. Kamath MP, Shenoy BD, Tiwari SB, Karki R, Udupa N, Kotian M. Prolonged release biodegradable vesicular carriers for rifampicin—formulation and kinetics of release. Indian J Exp Biol. 2000;38(2):113–8.

    CAS  Google Scholar 

  6. de Araujo DR, Cereda CM, Brunetto GB, Vomero VU, Pierucci A, Neto HS, et al. Pharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine. J Pharm Pharmacol. 2008;60(11):1449–57.

    Article  Google Scholar 

  7. de Araujo DR, Cereda CM, Brunetto GB, Pinto LM, Santana MH, de Paula E. Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice. Can J Anaesth. 2004;51(6):566–72.

    Article  Google Scholar 

  8. Cereda CM, de Araujo DR, Brunetto GB, De Paula E. Liposomal prilocaine: preparation, characterization, and in vivo evaluation. J Pharm Pharm Sci. 2004;7(2):235–40.

    CAS  Google Scholar 

  9. Grant GJ, Bansinath M. Liposomal delivery systems for local anesthetics. Reg Anesth Pain Med. 2001;26(1):61–3.

    Article  CAS  Google Scholar 

  10. Grant SA. The Holy Grail: long-acting local anaesthetics and liposomes. Best Pract Res Clin Anaesthesiol. 2002;16(2):345–52.

    Article  CAS  Google Scholar 

  11. Grant GJ, Barenholz Y, Bolotin EM, Bansinath M, Turndorf H, Piskoun B, et al. A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia. Anesthesiology. 2004;101(1):133–7.

    Article  CAS  Google Scholar 

  12. Mura P, Maestrelli F, Gonzalez-Rodriguez ML, Michelacci I, Ghelardini C, Rabasco AM. Development, characterization and in vivo evaluation of benzocaine-loaded liposomes. Eur J Pharm Biopharm. 2007;67(1):86–95.

    Article  CAS  Google Scholar 

  13. Bonora S, Trinchero A, Torreggiani A, Tamba M. A DSC and Raman study of the interaction between tricresyl phosphates (TCP) and phospholipid liposomes. Croat Chem Acta. 2007;80(1):81–9.

    CAS  Google Scholar 

  14. Anderson M, Omri A. The effect of different lipid components on the in vitro stability and release kinetics of liposome formulations. Drug Deliv. 2004;11(1):33–9.

    Article  CAS  Google Scholar 

  15. de Jong RH. Local anesthetics. 1st ed. St. Louis: Mosby-Year Book; 1994.

    Google Scholar 

  16. De Paula E, Schreier S. Use of a novel method for determination of partition-coefficients to compare the effect of local-anesthetics on membrane-structure. Biochem Biophys Acta. 1995;1240(1):25–33.

    Article  Google Scholar 

  17. Collins VJ. Principles of anesthesiology: general and regional anesthesia. 3rd ed. Philadelphia: Lea & Febiger; 1993.

    Google Scholar 

  18. Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165–9.

    Article  CAS  Google Scholar 

  19. Davio SR, Low PS. The effect of anesthetic charge on anesthetic-phospholipid interactions. Biochem Biophys Acta. 1981;644(2):157–64.

    Article  CAS  Google Scholar 

  20. Laouini A. Preparation, characterization and applications of liposomes: state of the art. J Colloid Sci Biotechnol. 2012;1:147–68.

    Article  CAS  Google Scholar 

  21. Cereda CM, Brunetto GB, de Araujo DR, de Paula E. Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration. Can J Anaesth. 2006;53(11):1092–7.

    Article  Google Scholar 

  22. Franz-Montan M, Baroni D, Brunetto G, Sobral VR, da Silva CM, Venancio P, et al. Liposomal lidocaine gel for topical use at the oral mucosa: characterization, in vitro assays and in vivo anesthetic efficacy in humans. J Liposome Res. 2015;25(1):11–9.

    Article  CAS  Google Scholar 

  23. Glavas-Dodov M, Goracinova K, Mladenovska K, Fredro-Kumbaradzi E. Release profile of lidocaine HCl from topical liposomal gel formulation. Int J Pharm. 2002;242(1–2):381–4.

    Article  CAS  Google Scholar 

  24. Mashimo T, Uchida I, Pak M, Shibata A, Nishimura S, Inagaki Y, et al. Prolongation of canine epidural anesthesia by liposome encapsulation of lidocaine. Anesth Analg. 1992;74(6):827–34.

    Article  CAS  Google Scholar 

  25. Sun NH, Zhu YY, Yuan L, Lang B. Nano-liposomes of entrapment lidocaine hydrochloride on in vitro permeability of narcotic. Pak J Pharm Sci. 2015;28(1):325–8.

    CAS  Google Scholar 

  26. Bano M. Determination of partition coefficient by the change of main phase transition. Gen Physiol Biophys. 2000;19(3):279–93.

    CAS  Google Scholar 

  27. Biltonen RL, Lichtenberg D. The use of differential scanning calorimetry as a tool to characterize liposome preparations. Chem Phys Lipids. 1993;64(1–3):129–42.

    Article  CAS  Google Scholar 

  28. Kaminoh Y, Tashiro C, Kamaya H, Ueda I. Depression of phase-transition temperature by anesthetics: nonzero solid membrane binding. Biochem Biophys Acta. 1988;946(2):215–20.

    Article  CAS  Google Scholar 

  29. Inoue T, Miyakawa K, Shimozawa R. Interaction of surfactants with vesicle membrane of dipalmitoylphosphatidylcholine. Effect on gel-to-liquid-crystalline phase transition of lipid bilayer. Chem Phys Lipids. 1986;42(4):261–70.

    Article  CAS  Google Scholar 

  30. Heerklotz H. Interactions of surfactants with lipid membranes. Q Rev Biophys. 2008;41(3–4):205–64.

    Article  CAS  Google Scholar 

  31. Redmanfurey NL, Antinore MJ. Determination of partition-coefficients between dimyristoylphosphatidylcholine and water using differential scanning calorimetry. Anal Chim Acta. 1991;251(1–2):79–81.

    Article  CAS  Google Scholar 

  32. Schurtenberger P, Lindman B. Coexistence of simple and mixed bile salt–lecithin micelles: an NMR self-diffusion study. Biochemistry. 1985;24(25):7161–5.

    Article  CAS  Google Scholar 

  33. Almog S, Kushnir T, Nir S, Lichtenberg D. Kinetic and structural aspects of reconstitution of phosphatidylcholine vesicles by dilution of phosphatidylcholine–sodium cholate mixed micelles. Biochemistry. 1986;25(9):2597–605.

    Article  CAS  Google Scholar 

  34. Cereda CMS, Tofoli GR, De Brito RB, De Jesus MB, Fraceto LF, Groppo FC, et al. Stability and local toxicity evaluation of a liposomal prilocaine formulation. J Liposome Res. 2008;18(4):329–39.

    Article  CAS  Google Scholar 

  35. Puranik SB, Pai R, Pai PNS, Rao GK. Gas chromatographic determination of residual levels of methanol and chloroform from liposomal, microspheres and nanoparticles. Int J Chem Sci. 2008;6(2):693–704.

    CAS  Google Scholar 

  36. Pathak P, Nagarsenker M. Formulation and evaluation of lidocaine lipid nanosystems for dermal delivery. AAPS PharmSciTech. 2009;10(3):985–92.

    Article  CAS  Google Scholar 

  37. Foldvari M, Gesztes A, Mezei M, Cardinal L, Kowalczyk I, Behl M. Topical liposomal local anesthetics: design, optimization and evaluation of formulations. Drug Dev Ind Pharm. 1993;19(19):2499–517.

    Article  CAS  Google Scholar 

  38. Fernandez MS. Formation of micelles and membrane action of the local anesthetic tetracaine hydrochloride. Biochem Biophys Acta. 1980;597(1):83–91.

    Article  CAS  Google Scholar 

  39. Stewart JC. Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Anal Biochem. 1980;104(1):10–4.

    Article  CAS  Google Scholar 

  40. Verma DD, Verma S, Blume G, Fahr A. Particle size of liposomes influences dermal delivery of substances into skin. Int J Pharm. 2003;258(1–2):141–51.

    Article  CAS  Google Scholar 

  41. Ionov M, Garaiova Z, Waczulikova I, Wrobel D, Pedziwiatr-Werbicka E, Gomez-Ramirez R, et al. siRNA carriers based on carbosilane dendrimers affect zeta potential and size of phospholipid vesicles. Biochem Biophys Acta. 2012;1818(9):2209–16.

    Article  CAS  Google Scholar 

  42. Foggia MD. DSC and Raman study of DMPC liposomes in presence of Ibuprofen at different pH. J Therm Anal Calorim. 2016;127(2):1407–17.

    Article  Google Scholar 

  43. Tenchov B. On the Reversibility of the phase-transitions in lipid–water systems. Chem Phys Lipids. 1991;57(2–3):165–77.

    Article  CAS  Google Scholar 

  44. Marsh D. Handbook of lipids bilayers. Boca Rata: CRC Press; 1990.

    Google Scholar 

  45. Panico AM, Santagati A, Cardile V, Urso D, Gentile B, Ronsisvalle G. Calorimetric study on the interaction of thienopyrimidine derivatives with phosphatidylcholine membranes. Colloid Surf B. 2003;28(1):77–81.

    Article  CAS  Google Scholar 

  46. Wang PY, Chen JW, Hwang F. Anisodamine causes acyl-chain interdigitation in phosphatidylglycerol. FEBS Lett. 1993;332(1–2):193–6.

    Article  CAS  Google Scholar 

  47. Pedersen TB, Frokjaer S, Mouritsen OG, Jorgensen K. A calorimetric study of phosphocholine membranes mixed with desmopressin and its diacylated prodrug derivative (DPP). Int J Pharm. 2002;233(1–2):199–206.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are thankful to the Erasmus+ Programme enabling the mobility to perform the experiments. The assistance of the workers of the Department of Pharmaceutical Technology and Biopharmacy (University of Freiburg) is highly appreciated. Supported BY the ÚNKP-16-3 New National Excellence Program of the Ministry of Human Capacities.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Erzsébet Csányi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bakonyi, M., Berkó, S., Budai-Szűcs, M. et al. DSC for evaluating the encapsulation efficiency of lidocaine-loaded liposomes compared to the ultracentrifugation method. J Therm Anal Calorim 130, 1619–1625 (2017). https://doi.org/10.1007/s10973-017-6394-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10973-017-6394-1

Keywords

Navigation