Preparation and Optimization of Vancomycin hydrochloride Encapsulated Multivesicular Liposomes for Sustained Locoregional Delivery
International Pharmacy Acta,
Vol. 4 No. 1 (2021),
2 June 2021
,
Page 4e6:1-12
https://doi.org/10.22037/ipa.v4i1.34461
Abstract
Introduction:
Osteomyelitis is a destructive inflammatory condition of the bone that is usually caused by a wide range of microorganisms especially Staphylococcus aureus. Considering the downsides of systemic antibiotic therapies as well as conventional local drug delivery systems such as using polymethylmethacrylate, this study aimed to develop, characterize and optimize vancomycin hydrochloride loaded multivesicular liposomes (MVLs) as a proper therapeutic option for the treatment of osteomyelitis.
Methods and Results:
A 23 full factorial design technique was applied to determine the effects of three variables (lipid to drug ratio, triolein content and cholesterol to phospholipid ratio) on the encapsulation efficiency and release profile of vancomycin hydrochloride loaded MVLs to optimize the final formulation. Further characterization was performed on the optimized formula by evaluating the morphology, size and storage stability. The average drug encapsulation efficiency and the mean diameter of the optimized formulation was 54.7 ± 0.3% and 9.019 ± 0.26 µm, respectively with a span value of 0.188. Additionally, the spherical and multivesicular nature of MVLs was visible using optical microscopy (x400). The optimized formula showed an in vitro sustained release characteristic with proper stability and insignificant change in size, morphology and EE% for 30 days at 4°C.
Conclusion:
This study suggests that vancomycin hydrochloride loaded MVLs might have the potential to be used in the treatment of chronic osteomyelitis as a biocompatible drug carrier with a high antibiotic entrapment capacity as well as controlled drug release.
Keywords:
- Vancomycin hydrochloride; Multivesicular liposomes; Osteomyelitis; Sustained release; Factorial design.
How to Cite
Vatankhah, M., Mahboubi, A., Haeri, A., Mostafavi Naeini, S. B., Abbasian, Z., & Dadashzadeh, S. (2021). Preparation and Optimization of Vancomycin hydrochloride Encapsulated Multivesicular Liposomes for Sustained Locoregional Delivery. International Pharmacy Acta, 4(1), 4e6:1–12. https://doi.org/10.22037/ipa.v4i1.34461
References
1 Ford CA, Cassat JE. Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis. Expert review of anti-infective therapy. 2017 Sep 2;15(9):851-60.
2 Gomes D, Pereira M, Bettencourt AF. Osteomyelitis: an overview of antimicrobial therapy. Brazilian Journal of Pharmaceutical Sciences. 2013 Mar;49(1):13-27.
3 Ambrose CG, Clyburn TA, Louden K, Joseph J, Wright J, Gulati P, Gogola GR, Mikos AG. Effective Treatment of Osteomyelitis with Biodegradable Microspheres in a Rabbit Model. Clinical Orthopaedics and Related Research (1976-2007). 2004 Apr 1;421:293-9.
4 Nandi SK, Bandyopadhyay S, Das P, Samanta I, Mukherjee P, Roy S, Kundu B. Understanding osteomyelitis and its treatment through local drug delivery system. Biotechnology advances. 2016 Dec 1;34(8):1305-17.
5 Cancienne, Jourdan M., et al. "Applications of local antibiotics in orthopedic trauma." Orthopedic Clinics 46.4 (2015): 495-510.
6 Ambrose CG, Gogola GR, Clyburn TA, Raymond AK, Peng AS, Mikos AG. Antibiotic microspheres: preliminary testing for potential treatment of osteomyelitis. Clinical Orthopaedics and Related Research®. 2003 Oct 1;415:279-85.
7 Yan, Ling, et al. "Treatment of Staphylococcus aureus-induced chronic osteomyelitis with bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres." Drug design, development and therapy 9 (2015): 3665.
8 Zhang, Lixue, et al. "Liraglutide-loaded multivesicular liposome as a sustained-delivery reduces blood glucose in SD rats with diabetes." Drug delivery 23.9 (2016): 3358-3363.
9 Beiranvand, Siavash, and Mahmoud Reza Moradkhani. "Bupivacaine versus liposomal bupivacaine for pain control." Drug research 68.07 (2018): 365-369.
10 Kim, Sinil, et al. "Direct cerebrospinal fluid delivery of an antiretroviral agent using multivesicular liposomes." Journal of Infectious Diseases 162.3 (1990): 750-752.
11 Liu, Junli, et al. "Liposomes for systematic delivery of vancomycin hydrochloride to decrease nephrotoxicity: Characterization and evaluation." asian journal of pharmaceutical sciences 10.3 (2015): 212-222.
12 Suchý, Tomáš, et al. "The release kinetics, antimicrobial activity and cytocompatibility of differently prepared collagen/hydroxyapatite/vancomycin layers: microstructure vs. nanostructure." European Journal of Pharmaceutical Sciences 100 (2017): 219-229.
13 Mantripragada, Sankaram. "A lipid based depot (DepoFoam® technology) for sustained release drug delivery." Progress in lipid research 41.5 (2002): 392-406.
14 Sun L, Wang T, Gao L, Quan D, Feng D. Multivesicular liposomes for sustained release of naltrexone hydrochloride: design, characterization and in vitro/in vivo evaluation. Pharm Dev Technol. 2013; 18(4): 828-833.
15 El-Say, Khalid Mohamed. "Maximizing the encapsulation efficiency and the bioavailability of controlled-release cetirizine microspheres using Draper–Lin small composite design." Drug design, development and therapy 10 (2016): 825.
16 Mutlu-Agardan, N. Basaran, et al. "Development of effective AmB/AmB–αCD complex double loaded liposomes using a factorial design for systemic fungal infection treatment." Journal of liposome research (2020): 1-12.
17 Akhlaghi, Sarah, et al. "Green formulation of curcumin loaded lipid-based nanoparticles as a novel carrier for inhibition of post-angioplasty restenosis." Materials Science and Engineering: C 105 (2019): 110037.
18 Li, Ning, et al. "Multivesicular liposomes for the sustained release of angiotensin I-converting enzyme (ACE) inhibitory peptides from peanuts: Design, characterization, and in vitro evaluation." Molecules 24.9 (2019): 1746.
19 Beach, Jessica E., et al. "Penetration of vancomycin into the cerebrospinal fluid: a systematic review." Clinical pharmacokinetics 56.12 (2017): 1479-1490.
20 Bajelan, Elmira, et al. "Co-delivery of doxorubicin and PSC 833 (Valspodar) by stealth nanoliposomes for efficient overcoming of multidrug resistance." Journal of Pharmacy & Pharmaceutical Sciences 15.4 (2012): 568-582.
21 Peram, Malleswara Rao, et al. "Factorial design based curcumin ethosomal nanocarriers for the skin cancer delivery: in vitro evaluation." Journal of liposome research 29.3 (2019): 291-311.
22 Mishra, Abha, Sunil Kumar, and Sudhir Kumar. "Application of Box-Benhken experimental design for optimization of laccase production by Coriolus versicolor MTCC138 in solid-state fermentation." (2008).
23 Godbole, Mangesh D., Prafulla M. Sabale, and Vijay B. Mathur. "Development of lamivudine liposomes by three-level factorial design approach for optimum entrapment and enhancing tissue targeting." Journal of Microencapsulation 37.6 (2020): 431-444.
24 Nayak, Amit Kumar, Dilipkumar Pal, and Kousik Santra. "Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of metformin HCl." International journal of biological macromolecules 65 (2014): 329-339.
25 Shen, Yan, et al. "Multivesicular liposome formulations for the sustained delivery of ropivacaine hydrochloride: preparation, characterization, and pharmacokinetics." Drug delivery 18.5 (2011): 361-366.
26 Jain, Sanjay K., et al. "Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium." AAPS pharmscitech 6.1 (2005): E35-E41.
27 Johnston, Michael JW, et al. "Influence of drug-to-lipid ratio on drug release properties and liposome integrity in liposomal doxorubicin formulations." Journal of liposome research 18.2 (2008): 145-157.
28 Luo, Yuling, et al. "Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo." International journal of nanomedicine 11 (2016): 3111.
29 Zhang, Miao, Ye-ling Yu, and Xing Tang. "Preparation and its release in vitro of multivesicular liposomes containing cytarabine." J. Shenyang Pharm. Univ 26 (2009): 1-5.
30 Briuglia, Maria-Lucia, et al. "Influence of cholesterol on liposome stability and on in vitro drug release." Drug delivery and translational research 5.3 (2015): 231-242.
31 Manna, Soumyarwit, et al. "Probing the mechanism of bupivacaine drug release from multivesicular liposomes." Journal of Controlled Release 294 (2019): 279-287.
32 Dorati, Rossella, et al. "An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery." Materials Science and Engineering: C 58 (2016): 909-917.
33 Gimeno, Marina, et al. "A controlled antibiotic release system to prevent orthopedic-implant associated infections: An in vitro study." European Journal of Pharmaceutics and Biopharmaceutics 96 (2015): 264-271.
34 Borcherding, Kai, et al. "Burst release of antibiotics combined with long-term release of silver targeting implant-associated infections: Design, characterization and in vitro evaluation of novel implant hybrid surface." Materials 12.23 (2019): 3838.
35 Yuvaraja, K., Sanjoy Kumar Das, and Jasmina Khanam. "Process optimization and characterization of carvedilol solid dispersion with hydroxypropyl-β-cyclodextrin and tartaric acid." Korean journal of chemical engineering 32.1 (2015): 132-140.
2 Gomes D, Pereira M, Bettencourt AF. Osteomyelitis: an overview of antimicrobial therapy. Brazilian Journal of Pharmaceutical Sciences. 2013 Mar;49(1):13-27.
3 Ambrose CG, Clyburn TA, Louden K, Joseph J, Wright J, Gulati P, Gogola GR, Mikos AG. Effective Treatment of Osteomyelitis with Biodegradable Microspheres in a Rabbit Model. Clinical Orthopaedics and Related Research (1976-2007). 2004 Apr 1;421:293-9.
4 Nandi SK, Bandyopadhyay S, Das P, Samanta I, Mukherjee P, Roy S, Kundu B. Understanding osteomyelitis and its treatment through local drug delivery system. Biotechnology advances. 2016 Dec 1;34(8):1305-17.
5 Cancienne, Jourdan M., et al. "Applications of local antibiotics in orthopedic trauma." Orthopedic Clinics 46.4 (2015): 495-510.
6 Ambrose CG, Gogola GR, Clyburn TA, Raymond AK, Peng AS, Mikos AG. Antibiotic microspheres: preliminary testing for potential treatment of osteomyelitis. Clinical Orthopaedics and Related Research®. 2003 Oct 1;415:279-85.
7 Yan, Ling, et al. "Treatment of Staphylococcus aureus-induced chronic osteomyelitis with bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres." Drug design, development and therapy 9 (2015): 3665.
8 Zhang, Lixue, et al. "Liraglutide-loaded multivesicular liposome as a sustained-delivery reduces blood glucose in SD rats with diabetes." Drug delivery 23.9 (2016): 3358-3363.
9 Beiranvand, Siavash, and Mahmoud Reza Moradkhani. "Bupivacaine versus liposomal bupivacaine for pain control." Drug research 68.07 (2018): 365-369.
10 Kim, Sinil, et al. "Direct cerebrospinal fluid delivery of an antiretroviral agent using multivesicular liposomes." Journal of Infectious Diseases 162.3 (1990): 750-752.
11 Liu, Junli, et al. "Liposomes for systematic delivery of vancomycin hydrochloride to decrease nephrotoxicity: Characterization and evaluation." asian journal of pharmaceutical sciences 10.3 (2015): 212-222.
12 Suchý, Tomáš, et al. "The release kinetics, antimicrobial activity and cytocompatibility of differently prepared collagen/hydroxyapatite/vancomycin layers: microstructure vs. nanostructure." European Journal of Pharmaceutical Sciences 100 (2017): 219-229.
13 Mantripragada, Sankaram. "A lipid based depot (DepoFoam® technology) for sustained release drug delivery." Progress in lipid research 41.5 (2002): 392-406.
14 Sun L, Wang T, Gao L, Quan D, Feng D. Multivesicular liposomes for sustained release of naltrexone hydrochloride: design, characterization and in vitro/in vivo evaluation. Pharm Dev Technol. 2013; 18(4): 828-833.
15 El-Say, Khalid Mohamed. "Maximizing the encapsulation efficiency and the bioavailability of controlled-release cetirizine microspheres using Draper–Lin small composite design." Drug design, development and therapy 10 (2016): 825.
16 Mutlu-Agardan, N. Basaran, et al. "Development of effective AmB/AmB–αCD complex double loaded liposomes using a factorial design for systemic fungal infection treatment." Journal of liposome research (2020): 1-12.
17 Akhlaghi, Sarah, et al. "Green formulation of curcumin loaded lipid-based nanoparticles as a novel carrier for inhibition of post-angioplasty restenosis." Materials Science and Engineering: C 105 (2019): 110037.
18 Li, Ning, et al. "Multivesicular liposomes for the sustained release of angiotensin I-converting enzyme (ACE) inhibitory peptides from peanuts: Design, characterization, and in vitro evaluation." Molecules 24.9 (2019): 1746.
19 Beach, Jessica E., et al. "Penetration of vancomycin into the cerebrospinal fluid: a systematic review." Clinical pharmacokinetics 56.12 (2017): 1479-1490.
20 Bajelan, Elmira, et al. "Co-delivery of doxorubicin and PSC 833 (Valspodar) by stealth nanoliposomes for efficient overcoming of multidrug resistance." Journal of Pharmacy & Pharmaceutical Sciences 15.4 (2012): 568-582.
21 Peram, Malleswara Rao, et al. "Factorial design based curcumin ethosomal nanocarriers for the skin cancer delivery: in vitro evaluation." Journal of liposome research 29.3 (2019): 291-311.
22 Mishra, Abha, Sunil Kumar, and Sudhir Kumar. "Application of Box-Benhken experimental design for optimization of laccase production by Coriolus versicolor MTCC138 in solid-state fermentation." (2008).
23 Godbole, Mangesh D., Prafulla M. Sabale, and Vijay B. Mathur. "Development of lamivudine liposomes by three-level factorial design approach for optimum entrapment and enhancing tissue targeting." Journal of Microencapsulation 37.6 (2020): 431-444.
24 Nayak, Amit Kumar, Dilipkumar Pal, and Kousik Santra. "Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of metformin HCl." International journal of biological macromolecules 65 (2014): 329-339.
25 Shen, Yan, et al. "Multivesicular liposome formulations for the sustained delivery of ropivacaine hydrochloride: preparation, characterization, and pharmacokinetics." Drug delivery 18.5 (2011): 361-366.
26 Jain, Sanjay K., et al. "Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium." AAPS pharmscitech 6.1 (2005): E35-E41.
27 Johnston, Michael JW, et al. "Influence of drug-to-lipid ratio on drug release properties and liposome integrity in liposomal doxorubicin formulations." Journal of liposome research 18.2 (2008): 145-157.
28 Luo, Yuling, et al. "Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo." International journal of nanomedicine 11 (2016): 3111.
29 Zhang, Miao, Ye-ling Yu, and Xing Tang. "Preparation and its release in vitro of multivesicular liposomes containing cytarabine." J. Shenyang Pharm. Univ 26 (2009): 1-5.
30 Briuglia, Maria-Lucia, et al. "Influence of cholesterol on liposome stability and on in vitro drug release." Drug delivery and translational research 5.3 (2015): 231-242.
31 Manna, Soumyarwit, et al. "Probing the mechanism of bupivacaine drug release from multivesicular liposomes." Journal of Controlled Release 294 (2019): 279-287.
32 Dorati, Rossella, et al. "An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery." Materials Science and Engineering: C 58 (2016): 909-917.
33 Gimeno, Marina, et al. "A controlled antibiotic release system to prevent orthopedic-implant associated infections: An in vitro study." European Journal of Pharmaceutics and Biopharmaceutics 96 (2015): 264-271.
34 Borcherding, Kai, et al. "Burst release of antibiotics combined with long-term release of silver targeting implant-associated infections: Design, characterization and in vitro evaluation of novel implant hybrid surface." Materials 12.23 (2019): 3838.
35 Yuvaraja, K., Sanjoy Kumar Das, and Jasmina Khanam. "Process optimization and characterization of carvedilol solid dispersion with hydroxypropyl-β-cyclodextrin and tartaric acid." Korean journal of chemical engineering 32.1 (2015): 132-140.
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