Gresha, A., Ramadan, A., Kassem, M., Khallafallah, N. (2024). Propylene glycol liposomes for improved delivery of vancomycin to biofilms on abiotic surfaces. test, 1(1), 121-137. doi: 10.21608/japs.2024.255619.1013
Amr E. Gresha; Alyaa A. Ramadan; Mervat A. Kassem; Nawal M. Khallafallah. "Propylene glycol liposomes for improved delivery of vancomycin to biofilms on abiotic surfaces". test, 1, 1, 2024, 121-137. doi: 10.21608/japs.2024.255619.1013
Gresha, A., Ramadan, A., Kassem, M., Khallafallah, N. (2024). 'Propylene glycol liposomes for improved delivery of vancomycin to biofilms on abiotic surfaces', test, 1(1), pp. 121-137. doi: 10.21608/japs.2024.255619.1013
Gresha, A., Ramadan, A., Kassem, M., Khallafallah, N. Propylene glycol liposomes for improved delivery of vancomycin to biofilms on abiotic surfaces. test, 2024; 1(1): 121-137. doi: 10.21608/japs.2024.255619.1013

Propylene glycol liposomes for improved delivery of vancomycin to biofilms on abiotic surfaces

Journal of Advanced Pharmaceutical Sciences
Volume 1, Issue 1, January 2024, Pages 121-137    PDF (1019.69 K)
Document Type: Original Article
DOI: 10.21608/japs.2024.255619.1013
Authors
Amr E. Gresha1; Alyaa A. Ramadan* 2; Mervat A. Kassem3; Nawal M. Khallafallah2
1Pharco Pharmaceuticals Co., Alexandria, Egypt
2Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt
3Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University
Abstract
Patients fitted with urinary bladder and vascular catheters are subject to bacterial infections and biofilm formation. These infections are mostly caused by coagulase-positive and coagulase-negative staphylococci. Vancomycin (VCM) remains the frontline intravenous antibiotic for the treatment of catheter-related bacteremia. Liposomes are appealing drug carrier systems, especially against colonized microorganisms.
In the present study, VCM-loaded propylene glycol liposomes were prepared by the ethanol injection method The liposomes were characterized pharmaceutically and microbiologically. Pharmaceutical attributes included colloidal properties, entrapment efficiency (EE%), release, and stability. Microbiological tests included the determination of Minimum Inhibitory Concentration (MIC) by two methods, antibiofilm efficacy using the microtiter plate model, including assessment of Minimum Biofilm Inhibitory Concentration (MBIC), Minimum Biofilm Eradicating Concentration (MBEC), and biofilm formation induction by vancomycin sub-minimum inhibitory concentrations. Antibiofilm efficacy was also assessed using the catheter segments model. VCM liposomes showed vesicle size in the nanorange (219.49 ± 20.21 nm), low PDI (0.282 ± 0.044), negative zeta potential (-4.78), and EE% (52.84±1.5%) that proved stable with no drug leakage after 3 months of storage at 4°C. It also showed a slower release profile compared to the free VCM. The antibacterial and antibiofilm efficacy of VCM liposomes compared to free VCM increased by 2–8 folds, calculated from the observed extent of reduction in MIC, MBIC, and MBEC of liposome-loaded VCM compared to free VCM. Results of catheter segment experiments indicated the potential usefulness of VCM liposomes in antibiotic lock solutions for managing biofilms on medical devices and implants.

Highlights
  • Drug delivery strategies have emerged as an effective approach for localized biofilm control on abiotic surfaces such as catheters.
  • Entrapment of antibiotics in liposomes may enhance their antimicrobial and antibiofilm activity.
  • Vancomycin-loaded propylene glycol liposomes were successfully prepared using the ethanol injection method.
  • The developed liposomes showed potential for use as a substitute for VCM in antibiotic lock solutions used to prevent or treat device-related bacteremias.
Keywords
Vancomycin; liposomes; abiotic; biofilm
References
  1. Barakat HS, Kassem MA, El-Khordagui LK, Khalafallah NM. Vancomycin-eluting niosomes: a new approach to the inhibition of staphylococcal biofilm on abiotic surfaces. AAPS PharmSciTech. 2014;15(5):1263-74.
  2. Nicolosi D, Scalia M, Nicolosi VM, Pignatello R. Encapsulation in fusogenic liposomes broadens the spectrum of action of vancomycin against Gram-negative bacteria. Int J Antimicrob Agents. 2010;35(6):553-8.
  3. Sanderson NM, Jones MN. Encapsulation of vancomycin and gentamicin within cationic liposomes for inhibition of growth of Staphylococcus epidermidis. J Drug Target. 1996;4(3):181-9.
  4. Scriboni AB, Couto VM, Ribeiro LNM, Freires IA, Groppo FC, de Paula E, et al. Fusogenic Liposomes Increase the Antimicrobial Activity of Vancomycin Against Staphylococcus aureus Biofilm. Front Pharmacol. 2019;10:1401.
  5. Ferreira M, Pinto SN, Aires-da-Silva F, Bettencourt A, Aguiar SI, Gaspar MM. Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms. Pharmaceutics. 2021;13(3).
  6. Makhlouf Z, Ali AA, Al-Sayah MH. Liposomes-Based Drug Delivery Systems of Anti-Biofilm Agents to Combat Bacterial Biofilm Formation. Antibiotics (Basel). 2023;12(5).
  7. Ferreira M, Ogren M, Dias JNR, Silva M, Gil S, Tavares L, et al. Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance. Molecules. 2021;26(7).
  8. Rukavina Z, Vanic Z. Current Trends in Development of Liposomes for Targeting Bacterial Biofilms. Pharmaceutics. 2016;8(2).
  9. Cangui-Panchi SP, Nacato-Toapanta AL, Enriquez-Martinez LJ, Reyes J, Garzon-Chavez D, Machado A. Biofilm-forming microorganisms causing hospital-acquired infections from intravenous catheter: A systematic review. Curr Res Microb Sci. 2022;3:100175.
  10. Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering RC, Jr., Eliopoulos GM. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol. 2004;42(6):2398-402.
  11. Donlan RM. Biofilms and device-associated infections. Emerg Infect Dis. 2001;7(2):277-81.
  12. Agarwal A, Singh KP, Jain A. Medical significance and management of staphylococcal biofilm. FEMS Immunol Med Microbiol. 2010;58(2):147-60.
  13. Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM. PG-liposomes: novel lipid vesicles for skin delivery of drugs. J Pharm Pharmacol. 2007;59(10):1447-50.
  14. Elmoslemany RM, Abdallah OY, El-Khordagui LK, Khalafallah NM. Propylene glycol liposomes as a topical delivery system for miconazole nitrate: comparison with conventional liposomes. AAPS PharmSciTech. 2012;13(2):723-31.
  15. Zhang L, Lu CT, Li WF, Cheng JG, Tian XQ, Zhao YZ, et al. Physical characterization and cellular uptake of propylene glycol liposomes in vitro. Drug Dev Ind Pharm. 2012;38(3):365-71.
  16. Abd El Azim H, Nafee N, Ramadan A, Khalafallah N. Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins. Int J Pharm. 2015;488(1-2):78-85.
  17. Nouruzi E, Hosseini SM, Asghari B, Mahjoub R, Zare EN, Shahbazi MA, et al. Effect of poly (lactic-co-glycolic acid) polymer nanoparticles loaded with vancomycin against Staphylococcus aureus biofilm. BMC Biotechnol. 2023;23(1):39.
  18. Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761-9.
  19. Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(1):1-45.
  20. Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999;37(6):1771-6.
  21. Yang K, Delaney JT, Schubert US, Fahr A. Fast high-throughput screening of temoporfin-loaded liposomal formulations prepared by ethanol injection method. J Liposome Res. 2012;22(1):31-41.
  22. Bergey DH. Bergey's manual of determinative bacteriology: Lippincott Williams & Wilkins; 1994.
  23. Woodbury DJ, Richardson ES, Grigg AW, Welling RD, Knudson BH. Reducing liposome size with ultrasound: bimodal size distributions. J Liposome Res. 2006;16(1):57-80.
  24. Berger N, Sachse A, Bender J, Schubert R, Brandl M. Filter extrusion of liposomes using different devices: comparison of liposome size, encapsulation efficiency, and process characteristics. Int J Pharm. 2001;223(1-2):55-68.
  25. Shah VP, Tsong Y, Sathe P, Liu J-P. In Vitro Dissolution Profile Comparison—Statistics and Analysis of the Similarity Factor, f2. Pharmaceutical Research. 1998;15(6):889-96.
  26. Moore J, Flanner H. Mathematical comparison of dissolution profiles. Pharmaceutical technology. 1996;20(6):64-74.
  27. Wayne P. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fourth Informational Supplement. CLSI Document M100-S24. M100-S24. 2014.
  28. Kojima N, Ishii M, Kawauchi Y, Takagi H. Construction and evaluation of bacteria-driven liposome. Sensors and Actuators B. 2013;183:395-400.
  29. Shashidhar GM, Manohar B. Nanocharacterization of liposomes for the encapsulation of water soluble compounds from Cordyceps sinensis CS1197 by a supercritical gas anti-solvent technique. RSC Adv. 2018;8(60):34634-49.
  30. Stepanovic S, Vukovic D, Dakic I, Savic B, Svabic-Vlahovic M. A modified microtiter-plate test for quantification of staphylococcal biofilm formation. J Microbiol Methods. 2000;40(2):175-9.
  31. Mekni MA, Bouchami O, Achour W, Ben Hassen A. Strong biofilm production but not adhesion virulence factors can discriminate between invasive and commensal Staphylococcus epidermidis strains. APMIS. 2012;120(8):605-11.
  32. Labthavikul P, Petersen PJ, Bradford PA. In vitro activity of tigecycline against Staphylococcus epidermidis growing in an adherent-cell biofilm model. Antimicrob Agents Chemother. 2003;47(12):3967-9.
  33. Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM. Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen. 2007;62(2):133-7.
  34. Sande L, Sanchez M, Montes J, Wolf AJ, Morgan MA, Omri A, Liu GY. Liposomal encapsulation of vancomycin improves killing of methicillin-resistant Staphylococcus aureus in a murine infection model. J Antimicrob Chemother. 2012;67(9):2191-4.
  35. Manconi M, Mura S, Sinico C, Fadda AM, Vila AO, Molina F. Development and characterization of liposomes containing glycols as carriers for diclofenac. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2009;342(1):53-8.
  36. Faustino P. Vancomycin solubility study. Report to office of generic drugs. 2008.
  37. Labhasetwar V, Mohan MS, Dorle AK. A study on zeta potential and dielectric constant of liposomes. J Microencapsul. 1994;11(6):663-8.
  38. Muppidi K, Pumerantz AS, Wang J, Betageri G. Development and stability studies of novel liposomal vancomycin formulations. ISRN Pharm. 2012;2012:636-743.
  39. Tamilvanan S, Venkateshan N, Ludwig A. The potential of lipid- and polymer-based drug delivery carriers for eradicating biofilm consortia on device-related nosocomial infections. J Control Release. 2008;128(1):2-22.
  40. Stewart PS. Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol. 2002;292(2):107-13.
  41. Castrillón Rivera Laura E, Palma Ramos A. Biofilms: A Survival and Resistance Mechanism of Microorganisms. In: Marina P, editor. Antibiotic Resistant Bacteria. Rijeka: IntechOpen; 2012. p. Ch. 7.
  42. Jardeleza C, Rao S, Thierry B, Gajjar P, Vreugde S, Prestidge CA, Wormald PJ. Liposome-encapsulated ISMN: a novel nitric oxide-based therapeutic agent against Staphylococcus aureus biofilms. PLoS One. 2014;9(3):e92117.
  43. Monzón M, Oteiza C, Leiva J, Lamata M, Amorena B. Biofilm testing of Staphylococcus epidermidis clinical isolates: low performance of vancomycin in relation to other antibiotics. Diagn Microbiol Infect Dis. 2002;44(4):319-24.
  44. Nejadnik MR, van der Mei HC, Norde W, Busscher HJ. Bacterial adhesion and growth on a polymer brush-coating. Biomaterials. 2008;29(30):4117-21.
  45. Sousa C, Botelho C, Oliveira R. Nanotechnology applied to medical biofilms control. Science Against Microbial Pathogens: Communicating Current Research and Technological Advances. 2011.
  46. Laureti L, Matic I, Gutierrez A. Bacterial Responses and Genome Instability Induced by Subinhibitory Concentrations of Antibiotics. Antibiotics (Basel). 2013;2(1):100-14.
  47. Beaulac C, Sachetelli S, Lagace J. In-vitro bactericidal efficacy of sub-MIC concentrations of liposome-encapsulated antibiotic against gram-negative and gram-positive bacteria. J Antimicrob Chemother. 1998;41(1):35-41.
  48. Donlan RM. Biofilm formation: a clinically relevant microbiological process. Clin Infect Dis. 2001;33(8):1387-92.
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