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Inflammation‐Induced Drug Release by using a pH‐Responsive Gas‐Generating Hollow‐Microsphere System for the Treatment of Osteomyelitis
Author(s) -
Chung MingFan,
Chia WeiTso,
Liu HungYi,
Hsiao ChunWen,
Hsiao HsuChan,
Yang ChihMan,
Sung HsingWen
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201400158
Subject(s) - osteomyelitis , calcium phosphate cement , plga , drug delivery , cement , penetration (warfare) , microsphere , aqueous solution , antibiotics , materials science , lactic acid , biomedical engineering , drug , bone cement , glycolic acid , calcium , chemistry , chemical engineering , bacteria , pharmacology , nanotechnology , surgery , composite material , medicine , organic chemistry , biochemistry , nanoparticle , engineering , biology , genetics , metallurgy , operations research
In the conventional treatment of osteomyelitis, the penetration of antibiotics into the infected bone is commonly poor. To ensure that the local antibiotic concentration is adequate, this work develops an injectable calcium phosphate (CP) cement in which is embedded pH‐responsive hollow microspheres (HMs) that can control the release of a drug according to the local pH. The HMs are fabricated using a microfluidic device, with a shell of poly( d,l ‐lactic‐ co ‐glycolic acid) (PLGA) and an aqueous core that contains vancomycin (Van) and NaHCO 3 . At neutral pH, the CP/HM cement elutes a negligible concentration of the drug. In an acidic environment, the NaHCO 3 that is encapsulated in the HMs reacts with the acid rapidly to generate CO 2 bubbles, disrupting the PLGA shells and thereby releasing Van locally in excess of a therapeutic threshold. The feasibility of using this CP/HM cement to treat osteomyelitis is studied using a rabbit model. Analytical results reveal that the CP/HM cement provides highly effective local antibacterial activity. Histological examination further verifies the efficacy of the treatment by the CP/HM cement. The above findings suggest that the CP/HM cement is a highly efficient system for the local delivery of antibiotics in the treatment of osteomyelitis.