Intra-discal vancomycin-loaded PLGA microsphere injection for MRSA discitis: an experimental study.
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 × 10(3) ± 1.22 × 10(3) CFU/g) than the intravenous injection group (7.51 × 10(4) ± 7.16 × 10(4) 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.


CONCLUSIONS
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.
Wang
Fei
F
Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai 200003, People's Republic of China. wangfeicy@live.cn
Ni
Bin
B
Zhu
Zhuangchen
Z
Liu
Fucun
F
Zhu
Yu-Zhao
YZ
Liu
Jun
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015169:Colony Count, Microbial; D015299:Discitis / Q000382:microbiology*; D019344:Lactic Acid; D055624:Methicillin-Resistant Staphylococcus aureus; D008863:Microspheres; D011091:Polyesters; D011108:Polymers; D011817:Rabbits; D013203:Staphylococcal Infections; D014640:Vancomycin / Q000008:administration & dosage*
D000900:Anti-Bacterial Agents; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D014640:Vancomycin