Alleviation of Surgery-Induced Osteitis in Sinonasal Cavity by Dexamethasone-Loaded Poly(lactic-<i>co</i>-glycolic acid) (PLGA) Microparticles with Strong Calcium-Binding Affinity
Seung-No Hong,
Minjae Kim,
Jin-A Park,
Minji Kang,
Hyunkyung Cha,
Sohyun Park,
Joon Kon Kim,
Jinyoung Pac,
Yuju Seo,
Sungwhan Kim,
Minju Kim,
Dae Woo Kim,
Yan Lee
Affiliations
Seung-No Hong
Department of Otolaryngology-Head and Neck Surgery, Seoul National University Boramae Medical Center, 5 Gil 20, Boramae-ro, Dongjak-gu, Seoul 07061, Korea
Minjae Kim
Department of Chemistry, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea
Jin-A Park
Department of Otolaryngology-Head and Neck Surgery, Seoul National University Boramae Medical Center, 5 Gil 20, Boramae-ro, Dongjak-gu, Seoul 07061, Korea
Minji Kang
Department of Chemistry, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea
Hyunkyung Cha
Department of Otolaryngology-Head and Neck Surgery, Seoul National University Boramae Medical Center, 5 Gil 20, Boramae-ro, Dongjak-gu, Seoul 07061, Korea
Sohyun Park
Department of Chemistry, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea
Joon Kon Kim
Department of Otolaryngology-Head and Neck Surgery, Daejeon Eulji Medical Center, Eulji University, Daejeon 35233, Korea
Jinyoung Pac
Department of Chemistry, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea
Yuju Seo
Department of Otolaryngology-Head and Neck Surgery, Chungnam National University Hospital, Chungnam National University, Daejeon 35015, Korea
Sungwhan Kim
Department of Chemistry, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea
Minju Kim
Department of Otolaryngology-Head and Neck Surgery, Seoul National University Boramae Medical Center, 5 Gil 20, Boramae-ro, Dongjak-gu, Seoul 07061, Korea
Dae Woo Kim
Department of Otolaryngology-Head and Neck Surgery, Seoul National University Boramae Medical Center, 5 Gil 20, Boramae-ro, Dongjak-gu, Seoul 07061, Korea
Yan Lee
Department of Chemistry, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea
For the treatment of sinus surgery-induced osteitis in chronic rhinosinusitis (CRS), oral or intranasal administration of corticoids is generally used, although it has critical limitations and unavoidable side effects. To overcome these limitations, we designed dexamethasone (Dex)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with bone-specific binding affinity, which could release the encapsulated Dex in a sustained manner on the exposed bone after the surgical wound in the nasal cavity. In a previous report, we prepared poly(butyl methacrylate-co-methacryloyloxyethyl phosphate) (PBMP) with both calcium-binding phosphomonoester groups and PLGA-binding butyl groups to introduce strong calcium-binding property to PLGA particles. In this study, after successful encapsulation of Dex in the PBMP-coated PLGA particles, we applied the Dex-PLGA/PBMP to the treatment of post-operative osteitis in the sinonasal cavity. The Dex-PLGA/PBMP showed more than 5-times higher binding affinity to the hydroxyapatite (HA) surface compared to the non-coated PLGA particles, without altering the morphology and encapsulation efficiency. After establishing the neo-osteogenesis mouse model by mechanical injury of the nasal mucosa, the activity of intranasally administered Dex-PLGA/PBMP was examined to inhibit the formation of undesirable new woven bone during the wound healing process. In addition, significantly lower osteocalcin activity was observed in the group treated with Dex-PLGA/PBMP, indicating decreased activation of osteoblasts. Overall, these results demonstrate that the PLGA/PBMP microparticle strategy has great potential for the treatment of CRS-related osteitis by localized corticoid delivery on the exposed bones with minimal side effects.
