Abstract
Objective
To prepare the vancomycin hydrochloride (VA)-loaded poly lactic acid-glycolic acid (PLGA) copolymer microsphere by the multiple emulsion method and evaluate its therapeutic effects on infective discitis.
Methods
Firstly, the particle diameter distribution, shape, encapsulation efficiency, drug-loaded dosage and release curve of VA-PLGA microspheres were evaluated in vitro. Rabbits with methicillin-resistant Staphylococcus aureus infective discitis were treated with VA-PLGA intra-discal injection. Meanwhile, VA intravenous injection, blank PLGA microspheres intra-discal injection served as controls. Thirty days later, therapeutic effects were evaluated through X-ray radiophotography, histopathological and bacteriological examination.
Results
Mean particle diameter was between 61.57 ± 4.37 and 67.45 ± 8.13 μm, and mean encapsulation efficiency was between 60.20 ± 1.61 and 75.27 ± 1.60 %m/m. In vitro release experiment showed that the release time was over 30 days. The result of in vivo experiment showed that inflammatory reaction in the VA-PLGA intra-discal injection group was milder than the intravenous injection group (P < 0.05), also with less inflammation. The bacterial count was also significantly lower (1.02 × 103 ± 1.22 × 103 CFU/g) than the intravenous injection group (7.51 × 104 ± 7.16 × 104 CFU/g) (P < 0.05). Besides these data, the amount used in VA-PLGA intra-discal injection group is about 20 mg, and that used in the intravenous injection group is about 2.4 g. So, we just use 1/120 of VA i.v. to obtain the better results with our microparticles.
Conclusion
Intra-discal injection with VA-PLGA sustained-release microspheres can use much less dosage, and effectively control and reduce infective discitis, and the therapeutic effect is superior to that of intravenous injection. A need for the clinical trials will be carried out in the near future.
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References
Khan IA, Vaccaro AR, Zlotolow DA (1999) Management of vertebral diskitis and osteomyelitis. Orthopedics 22(8):758–765
Lam KS, Webb JK (2004) Discitis. Hosp Med 65(5):280–286
Wirtz DC, Genius I, Wildberger JE et al (2000) Diagnostic and therapeutic management of lumbar and thoracic spondylodiscitis—an evaluation of 59 cases. Arch Orthop Trauma Surg 120(5–6):245–251
Hadjipavlou AG, Mader JT, Necessary JT et al (2000) Haematogenous pyogenic spinal infections and their surgical management. Spine 25(13):1668–1679
Hopkinson N, Stevenson J, Benjamin S (2001) A case ascertainment study of septic discitis: clinical, microbiological and radiological features. Q J Med 94:465–470
Johnson KD, Johnston DW (1989) Orthopedic experience with methicillin-resistant Staphylococcus aureus during a hospital epidemic. Clin Orthop 212:281–288
Osti OL, Fraser RD, Vernon-Roberts B (1990) Discitis after discography. The role of prophylactic antibiotics. J Bone Joint Surg [Br] 72:271–274
Pobiel RS, Schellhas KP, Pollei SR et al (2006) Diskography: infectious complications from a series of 12,634 cases. Am J Neuroradiol 27:1930–1932
Staatz G, Adam GB et al (1998) Spondylodiskitic abscesses: CT-guided percutaneous catheter drainage. Radiology 208(2):363–367
Mendel V, Simanovski HJ, Scholz HC et al (2005) Therapy with gentamycin-PMMA beads, gentamycin-collagen sponge, and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats. Arch Orthop Trauma Surg 125:363–368
Cevher E, Orhan Z, Mülazımoğlu L et al (2006) Characterization of biodegradable chitosan microspheres containing vancomycin and treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with prepared microspheres. Int J Pharm 317:127–135
Orhan Z, Cevher E, Yıldız A et al (2010) Biodegradable microspherical implants containing teicoplanin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis. Arch Orthop Trauma Surg 130:135–142
Jacob E, Setterstrom JA, Bach DE et al (1991) Evaluation of biodegradable ampicillin anhydrate microcapsules for local treatment of experimental staphylococcal osteomyelitis. Clin Orthop Relat Res 267:237–244
Virto MR, Elorza B, Torrado S et al (2007) Improvement of gentamicin poly(d,l-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures. Biomaterials 28(5):877–885
Hanssen AD (2005) Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. Clin Orthop Relat Res 437:91–96
Ozalp Y, Ozdemir N, Kocagöz S et al (2001) Controlled release of vancomycin from biodegradable microcapsules. J Microencapsul 18(1):89–110
Jameela SR, Suma N, Jayakrishnan A (1997) Protein release from poly(epsilon-caprolactone) microspheres prepared by melt encapsulation and solvent evaporation techniques: a comparative study. J Biomater Sci Polym Ed 8(6):457–466
Yang YY, Chung TS, Ng NP (2001) Morphology, drug distribution, and in vitro release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. Biomaterials 22(3):231–241
Willems PC, Jacobs W, Duinkerke ES et al (2004) Lumbar discography: should we use prophylactic antibiotics? A study of 435 consecutive discograms and a systematic review of the literature. J Spinal Disord Tech 17:243–247
Buchholz HW, Engelbrecht H (1970) Depot effects of various antibiotics mixed with palacos resins. Chirurg 41:511–515
Aimin C, Chunlin H, Juliang B et al (1999) Antibiotic loaded chitosan bar: an in vitro, in vivo study of a possible treatment for osteomyelitis. Clin Orthop 366:239–247
Ambrose CG, Gogola GR, Clyburn TA et al (2003) Antibiotic microspheres: preliminary testing for potential treatment of osteomyelitis. Clin Orthop 415:279–285
Calhoun JH, Mader JT (1997) Treatment of osteomyelitis with a biodegradable antibiotic implant. Clin Orthop 341:206–214
Garvin KL, Miyano JA, Robinson D et al (1994) Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis: a canine model. J Bone Joint Surg Am 76(10):1500–1506
Kanellakopoulou K, Giamarellos-Bourboulis E (2000) Carrier systems for the local delivery of antibiotics in bone infections. Drugs 59(6):1223–1232
Singh M, Shirley B, Bajwa K et al (2001) Controlled release of recombinant insulin-like growth factor from a novel formulation of polylactide-co-glycolide microparticles. J Control Release 70:21–28
Jain RA (2000) The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21:2475–2490
Prior S, Gamazo C, Irache JM et al (2000) Gentamicin encapsulation in PLA/PLGA microspheres in view of treating Brucella infections. Int J Pharm 196:115–125
Blanco-Prieto MJ, Lecaroz C, Renedo MJ et al (2002) In vitro evaluation of gentamicin released from microparticles. Int J Pharm 242:203–206
Freitas S, Merkle HP, Gander B (2005) Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microspheres preparation process technology. J Control Release 102:313–332
Ramchandani M, Pankaskie M, Robinson D (1997) The influence of manufacturing procedure on the degradation of poly(lactide-co-glycolide) 85:15 and 50:50 implants. J Control Release 43:161–173
Siepmann J, Faisant N, Akiki J et al (2004) Effect of the sizes of biodegradable microparticles of drug release: experiment and theory. J Control Release 96:123–134
Klose D, Siepmann F, Elkharraz K et al (2006) How porosity and size affect the drug release mechanisms from PLGA-based microparticles. Int J Pharm 314:198–206
Blanco-Prieto MJ, Leo E, Delie FG et al (1996) Study of the influence of several stabilizing agents on the entrapment and in vitro release of pBC 264 from poly(lactide-co-glycolide) microspheres prepared by a W/O/W solvent evaporation method. Pharm Res 13(7):1127–1129
Bierry G, Jehl F, Prévost G et al (2008) Percutaneous inoculated rabbit model of intervertebral disc space infection: magnetic resonance imaging features with pathological correlation. Joint Bone Spine 75(4):465–470
Scuderi GJ, Greenberg SS, Banovac K (1993) Penetration of glycopeptide antibiotics in nucleus pulposus. Spine (Phila Pa 1976) 18(14):2039–2042
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Wang, F., Ni, B., Zhu, Z. et al. Intra-discal vancomycin-loaded PLGA microsphere injection for MRSA discitis: an experimental study. Arch Orthop Trauma Surg 131, 111–119 (2011). https://doi.org/10.1007/s00402-010-1154-8
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DOI: https://doi.org/10.1007/s00402-010-1154-8