Inflammation-induced drug release by using a pH-responsive gas-generating hollow-microsphere system for the treatment of osteomyelitis.
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 NaHCO3. At neutral pH, the CP/HM cement elutes a negligible concentration of the drug. In an acidic environment, the NaHCO3 that is encapsulated in the HMs reacts with the acid rapidly to generate CO2 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.
Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan, ROC.
Ming-Fan
MF
Chung
Wei-Tso
WT
Chia
Hung-Yi
HY
Liu
Chun-Wen
CW
Hsiao
Hsu-Chan
HC
Hsiao
Chih-Man
CM
Yang
Hsing-Wen
HW
Sung
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001843:Bone Cements / Q000737:chemistry* / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000737:chemistry; D002245:Carbon Dioxide / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D005740:Gases / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000188:drug therapy*; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D010019:Osteomyelitis / Q000188:drug therapy*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D014640:Vancomycin / Q000008:administration & dosage / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001843:Bone Cements; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005740:Gases; D002245:Carbon Dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014640:Vancomycin; C020243:calcium phosphate
anti-inflammation; inflammatory diseases; local drug delivery; smart carriers; stimuli-responsive materials